| 1. |
|
|
| 2. |
- Cooper-Kuhn, Christiana M, 1971, et al.
(författare)
-
Decreased neurogenesis after cholinergic forebrain lesion in the adult rat.
- 2004
-
Ingår i: Journal of neuroscience research. - : Wiley. - 0360-4012 .- 1097-4547. ; 77:2, s. 155-65
-
Tidskriftsartikel (refereegranskat)abstract
- Adult neurogenesis has been shown to be regulated by a multitude of extracellular cues, including hormones, growth factors, and neurotransmitters. The cholinergic system of the basal forebrain is one of the key transmitter systems for learning and memory. Because adult neurogenesis has been implicated in cognitive performance, the present work aims at defining the role of cholinergic input for adult neurogenesis by using an immunotoxic lesion approach. The immunotoxin 192IgG-saporin was infused into the lateral ventricle of adult rats to selectively lesion cholinergic neurons of the cholinergic basal forebrain (CBF), which project to the two main regions of adult neurogenesis: the dentate gyrus and the olfactory bulb. Five weeks after lesioning, neurogenesis, defined by the number of cells colocalized for bromodeoxyuridine (BrdU) and the neuronal nuclei marker NeuN, declined significantly in the granule cell layers of the dentate gyrus and olfactory bulb. Furthermore, immunotoxic lesions to the CBF led to increased numbers of apoptotic cells specifically in the subgranular zone, the progenitor region of the dentate gyrus, and within the periglomerular layer of the olfactory bulb. We propose that the cholinergic system plays a survival-promoting role for neuronal progenitors and immature neurons within regions of adult neurogenesis, similar to effects observed previously during brain development. As a working hypothesis, neuronal loss within the CBF system leads not only to cognitive deficits but may also alter on a cellular level the functionality of the dentate gyrus, which in turn may aggravate cognitive deficits.
|
|
| 3. |
- Kuhn, Hans-Georg, 1961, et al.
(författare)
-
Bromodeoxyuridine and the detection of neurogenesis.
- 2007
-
Ingår i: Current pharmaceutical biotechnology. - 1873-4316. ; 8:3, s. 127-31
-
Forskningsöversikt (refereegranskat)abstract
- Bromodeoxyuridine (BrdU) is widely used for labeling dividing cells to determine their fate. In particular, the analysis of neurogenesis in the adult mammalian brain has made significant progress through the use of this technique. However; when using BrdU for labeling, there are several issues to consider in order to minimalize possible cytotoxicity or false-positive labeling. This current review summarizes methodological and technical aspects of BrdU administration and detection, compares alternative methods and gives recommendations on how to avoid labeling artifacts.
|
|
| 4. |
- Kuhn, Hans-Georg, 1961, et al.
(författare)
-
Changes in neurogenesis in dementia and Alzheimer mouse models: are they functionally relevant?
- 2007
-
Ingår i: European archives of psychiatry and clinical neuroscience. - : Springer Science and Business Media LLC. - 0940-1334 .- 1433-8491. ; 257:5, s. 281-9
-
Forskningsöversikt (refereegranskat)abstract
- Alzheimer's disease and related dementias are devastating disorders that lead to the progressive decline of cognitive functions. Characteristic features are severe brain atrophy, paralleled by accumulation of beta amyloid and neurofibrillary tangles. With the discovery of neurogenesis in the adult brain, the hopes have risen that these neurodegenerative conditions could be overcome, or at least ameliorated, by the generation of new neurons. The location of the adult neurogenic zones in the hippocampus and the lateral ventricle wall, close to corpus callosum and neocortex, indicates strategic positions for potential repair processes. However, we also need to consider that the generation of new neurons is possibly involved in cognitive functions and could, therefore, be influenced by disease pathology. Moreover, aberrant neurogenic mechanisms could even be a part of the pathological events of neurodegenerative diseases. It is the scope of this review to summarize and analyze the recent data from neurogenesis research with respect to Alzheimer's disease and its animal models.
|
|
| 5. |
|
|
| 6. |
- Lindberg, Olle R, et al.
(författare)
-
Characterization of Epidermal Growth Factor-Induced Dysplasia in the Adult Rat Subventricular Zone.
- 2012
-
Ingår i: Stem cells and development. - : Mary Ann Liebert Inc. - 1557-8534 .- 1547-3287. ; 21:8, s. 1356-1366
-
Tidskriftsartikel (refereegranskat)abstract
- Epidermal growth factor (EGF) is a mitogen widely used when culturing adult neural stem cells in vitro. Although proliferative effects can also be observed in vivo, intracerebroventricular infusion of EGF has been found to counteract neuronal determination and promote glial differentiation instead. However, EGF receptor activation has different effects on the subventricular zone (SVZ) in mice and rats, possibly because of species differences in SVZ cell composition. Specifically in the rat, EGF stimulation of the SVZ induces the formation of hyperplastic polyps. The present study aims at molecular and morphological characterization of these subventricular polyps. Using immunohistochemistry, electron microscopy, and gene expression analysis, we demonstrate in hyperplastic EGF-induced polyps an upregulation in protein expression of Sox2, Olig2, GFAP, nestin, and vimentin. We found polyp-specific dysplastic changes in the form of coexpression of Sox2 and Olig2. This highly proliferative, Sox2/Olig2 coexpressing dysplastic cell type is >10-fold enriched in the hyperplastic polyps compared with control SVZ and most likely causes the polyp formation. Unique ultrastructural features of the polyps include a lack of ependymal cell lining as well as a large number of cells with large, light, ovoid nuclei and a cytoplasm with abundant ribosomes, whereas other polyp cells contain invaginated nuclei but fewer ribosomes. EGF also induced changes in the expression of Id genes Id1, Id2, and Id4 in the SVZ. Taken together, we here demonstrate dysplastic, structural, and phenotypical changes in the rat SVZ following EGF stimulation, which are specific to hyperplastic polyps.
|
|
| 7. |
- Liu, Johan, 1960, et al.
(författare)
-
Stem Cell Growth and Migration on Nanofibrous Polymer Scaffolds and Micro-Fluidic Channels on Silicon-Chip
- 2009
-
Ingår i: Proceedings of the 2009 Electronic Components and Technology Conference. - 0569-5503. - 9781424444762 ; , s. 1080-1085
-
Konferensbidrag (refereegranskat)abstract
- Stem cell growth and migration on nanofibrous scaffolds and micro-fluidic channels on Silicon-Chip were studied by using neural stem cells isolated from adult rats' brain. Electrospinning and lithographic technique were used for developing nanofibrous-polylactic acid (PLA) and polyurethane (PU) based-scaffolds and micro-fluidic channels on Si-Chips respectively. Immunocytochemical and morphological analysis showed better cell-matrix interaction with profound adhesion, proliferation and migration on the developed scaffolds. Cell culture assay with microfluidic channel revealed the ability of developed channel system in guiding neuronal stem cell growth towards specified directions. These studies extend the possibility of using developed nanofibrous scaffolds and micro-fluidic channel system for future electrical signal transmission based on living neural stem cells.
|
|
| 8. |
- Nyberg, Jenny, 1976, et al.
(författare)
-
Anxiety severity and cognitive function in primary care patients with anxiety disorder: a cross-sectional study.
- 2021
-
Ingår i: BMC psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 21:1
-
Tidskriftsartikel (refereegranskat)abstract
- Deficits in cognitive performance are reported in patients with anxiety disorders, but research is limited and inconsistent. We aimed to investigate cross-sectional associations between cognitive function, with focus on executive function, and anxiety severity in primary care patients diagnosed with anxiety disorders.189 Swedish patients aged 18-65years (31% men) with anxiety disorders diagnosed according to Mini International Neuropsychiatric Interview were included. Severity of anxiety was assessed using Beck Anxiety Inventory self-assessment scale. Digit span, block design and matrix reasoning tests from the Wechsler Adult Intelligence Scale IV, and the design fluency test from the Delis-Kaplan Executive Function System were used. Multivariable linear regression models were applied to investigate the relationship of anxiety severity and cognitive functioning. Comparisons were also performed to a normed non-clinical population, using the Wilcoxon signed rank test.More severe anxiety was associated with lower digit span test scores (R2=0.109, B=-0.040, p=0.018), but not with block design, matrix reasoning or design fluency tests scores, after adjustment for comorbid major depression in a multivariable model. When compared to a normed population, patients with anxiety performed significantly lower on the block design, digit span forward, digit span sequencing and matrix reasoning tests.Severity of anxiety among patients with anxiety disorder was associated with executive functions related to working memory, independently of comorbid major depression, but not with lower fluid intelligence. A further understanding of the executive behavioral control in patients with anxiety could allow for more tailored treatment strategies including medication, therapy and interventions targeted to improve specific cognitive domains.
|
|
| 9. |
- Qiu, L., et al.
(författare)
-
Less neurogenesis and inflammation in the immature than in the juvenile brain after cerebral hypoxia-ischemia
- 2007
-
Ingår i: J Cereb Blood Flow Metab. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 27:4, s. 785-94
-
Tidskriftsartikel (refereegranskat)abstract
- The effects of hypoxia-ischemia (HI) on proliferation and differentiation in the immature (postnatal day 9) and juvenile (postnatal day 21) mouse hippocampus were investigated by injecting bromodeoxyuridine (50 mg/kg) daily for 7 days after the insult and evaluating the labeling 5 weeks after HI. Phenotypic differentiation was evaluated using NeuN, Iba1, APC, and S100beta as markers of neurons, microglia, oligodendrocytes, and astrocytes, respectively. The basal proliferation, in particular neurogenesis, was higher in the immature than in the juvenile hippocampus. Hypoxia-ischemia did not increase neurogenesis significantly in the immature dentate gyrus (DG), but it increased several-fold in the juvenile brain, reaching the same level as in the normal, noninjured immature brain. This suggests that the immature hippocampus is already working at the top of its proliferative capacity and that even though basal neurogenesis decreased with age, the injury-induced generation of new neurons in the juvenile hippocampus could not increase beyond the basal level of the immature brain. Generation of glial cells of all three types after HI was significantly more pronounced in the cornu ammonis of the hippocampus region of the juvenile hippocampus. In the DG, only microglia production was greater in the juvenile brain. Increased microglia proliferation correlated with increased levels of the proinflammatory cytokines MCP-1 and IL-18 3 days after HI, indicating that the inflammatory response is stronger in the juvenile hippocampus. In summary, contrary to what has been generally assumed, our results indicate that the juvenile brain has a greater capacity for neurogenesis after injury than the immature brain.
|
|
| 10. |
- Schäbitz, Wolf-Rüdiger, et al.
(författare)
-
Intravenous brain-derived neurotrophic factor enhances poststroke sensorimotor recovery and stimulates neurogenesis.
- 2007
-
Ingår i: Stroke; a journal of cerebral circulation. - 1524-4628. ; 38:7, s. 2165-72
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: The discovery of spontaneous neuronal replacement in the adult brain has shifted experimental stroke therapies toward a combined approach of preventing neuronal cell death and inducing neuronal plasticity. Brain-derived neurotrophic factor (BDNF) was shown to induce antiapoptotic mechanisms after stroke and to reduce infarct size and secondary neuronal cell death. Moreover, in intact animals, BDNF is a potent stimulator of adult neurogenesis. METHODS: The current study analyzed the effects of BDNF on induction of neuronal progenitor cell migration and sensorimotor recovery after cortical photothrombotic stroke. RESULTS: Daily intravenous bolus applications of BDNF during the first 5 days after stroke resulted in significantly improved sensorimotor scores up to 6 weeks. At the structural level, BDNF significantly increased neurogenesis in the dentate gyrus and enhanced migration of subventricular zone progenitor cells to the nearby striatum of the ischemic hemisphere. BDNF treatment could not, however, further stimulate progenitor cell recruitment to the cortex. CONCLUSIONS: These findings consolidate the role of BDNF as a modulator of neurogenesis in the brain and as an enhancer of long-term functional neurological outcome after cerebral ischemia.
|
|
| 11. |
- Schänzer, Anne, et al.
(författare)
-
Direct stimulation of adult neural stem cells in vitro and neurogenesis in vivo by vascular endothelial growth factor.
- 2004
-
Ingår i: Brain pathology (Zurich, Switzerland). - 1015-6305. ; 14:3, s. 237-48
-
Tidskriftsartikel (refereegranskat)abstract
- Hypoxia as well as global and focal ischemia are strong activators of neurogenesis in the adult mammalian central nervous system. Here we show that the hypoxia-inducible vascular endothelial growth factor (VEGF) and its receptor VEGFR-2/Flk-1 are expressed in clonally-derived adult rat neural stem cells in vitro. VEGF stimulated the expansion of neural stem cells whereas blockade of VEGFR-2/Flk-1-kinase activity reduced neural stem cell expansion. VEGF was also infused into the lateral ventricle to study changes in neurogenesis in the ventricle wall, olfactory bulb and hippocampus. Using a low dose (2.4 ng/d) to avoid endothelial proliferation and changes in vascular permeability, VEGF stimulated adult neurogenesis in vivo. After VEGF infusion, we observed reduced apoptosis but unaltered proliferation suggesting a survival promoting effect of VEGF in neural progenitor cells. Strong expression of VEGFR-2/Flk-1 was detected in the ventricle wall adjacent to the choroid plexus, a site of significant VEGF production, which suggests a paracrine function of endogenous VEGF on neural stem cells in vivo. We propose that VEGF acts as a trophic factor for neural stem cells in vitro and for sustained neurogenesis in the adult nervous system.These findings may have implications for the pathogenesis and therapy of neurodegenerative diseases.
|
|
| 12. |
- Walser, Marion, 1961, et al.
(författare)
-
Brain tissue haemoglobin expression in saline-perfused vs non-perfused rodents
- 2024
-
Ingår i: Heliyon. - 2405-8440. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- Haemoglobin beta (Hbb) and delta-aminolevulinate synthase 2 (Alas2) messenger RNA (mRNA) is mainly found in immature red blood cells, reticulocytes, and not in mature erythrocytes. However, these are also expressed in other tissues such as brain cells, mostly neurons. Therefore, exact quantification of neural tissue homogenates may be confounded by remaining blood in the brain vasculature that may give falsely high values of Hbb/Alas2 expression. To investigate and compare the contribution of local Hbb/Alas2 expression, we investigated mRNA expression locally in the hippocampus and prefrontal cortex, in post-sacrifice saline-perfused and non-perfused mice and rats. Although there was a higher level of Hbb/Alas2 transcripts in the non-perfused animals, there was a significant mRNA expression in perfused brains that could at most partially be explained by remaining blood. Finally, we suggest that saline-perfusion should be recommended for quantification of brain Hbb/Alas2 transcripts in homogenates.
|
|
| 13. |
- Walser, Marion, 1961, et al.
(författare)
-
Growth Hormone and Neuronal Hemoglobin in the Brain-Roles in Neuroprotection and Neurodegenerative Diseases
- 2021
-
Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- In recent years, evidence for hemoglobin (Hb) synthesis in both animal and human brains has been accumulating. While circulating Hb originating from cerebral hemorrhage or other conditions is toxic, there is also substantial production of neuronal Hb, which is influenced by conditions such as ischemia and regulated by growth hormone (GH), insulin-like growth factor-I (IGF-I), and other growth factors. In this review, we discuss the possible functions of circulating and brain Hb, mainly the neuronal form, with respect to the neuroprotective activities of GH and IGF-I against ischemia and neurodegenerative diseases. The molecular pathways that link Hb to the GH/IGF-I system are also reviewed, although the limited number of reports on this topic suggests a need for further studies. In summary, GH and/or IGF-I appear to be significant determinants of systemic and local brain Hb concentrations through mediating responses to oxygen and metabolic demand, as part of the neuroprotective effects exerted by GH and IGF-I. The nature and quantity of the latter deserve further exploration in specific experiments.
|
|
| 14. |
- Zhang, Liqun, et al.
(författare)
-
Effects of postnatal thyroid hormone deficiency on neurogenesis in the juvenile and adult rat.
- 2009
-
Ingår i: Neurobiology of disease. - : Elsevier BV. - 1095-953X .- 0969-9961. ; 34:2, s. 366-74
-
Tidskriftsartikel (refereegranskat)abstract
- This study addressed the influence of propylthiouracil (PTU)-induced hypothyroidism on postnatal and adult neurogenesis. PTU was administered from birth to postnatal day 10 (P10) or P21, leading to decreased neural stem cell/progenitor proliferation in the dentate gyrus, as well as significantly fewer granule cells and reduced hippocampal volume. Upon P22 PTU withdrawal, plasma thyroid hormone levels were normal by P90, there was no difference in the number of dentate gyrus or subventricular proliferating cells, but brain weight was smaller. In addition, dentate gyrus density of surviving BrdU-labeled cells increased, with no changes to the olfactory bulb. Quantitative PCR revealed decreased FGF-2, NGF, Wnt3a, and VEGF-A hippocampal expression during PTU treatment, with recovery in adulthood. Pro-apoptotic Bax was up-regulated, and anti-apoptotic Bcl-2 was down-regulated, during PTU treatment, both of which were normalized in the adult brain. In contrast, apoptosis-inducing factor (AIF) was down-regulated in the adult. These results suggest that mechanisms in the adult brain attempt to compensate for decreased neurogenesis due to postnatal hypothyroidism.
|
|
| 15. |
- Zhang, Liqun, et al.
(författare)
-
Stimulatory effects of thyroid hormone on brain angiogenesis in vivo and in vitro.
- 2010
-
Ingår i: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 1559-7016. ; 30:2, s. 323-35
-
Tidskriftsartikel (refereegranskat)abstract
- Thyroid hormone is critical for the proper development of the central nervous system. However, the specific role of thyroid hormone on brain angiogenesis remains poorly understood. Treatment of rats from birth to postnatal day 21 (P21) with propylthiouracil (PTU), a reversible blocker of triiodothyronine (T3) synthesis, resulted in decreased brain angiogenesis, as indicated by reduced complexity and density of microvessels. However, when PTU was withdrawn at P22, these parameters were fully recovered by P90. These changes were paralleled by an altered expression of vascular endothelial growth factor A (Vegfa) and basic fibroblast growth factor (Fgf2). Physiologic concentrations of T3 and thyroxine (T4) stimulated proliferation and tubulogenesis of rat brain-derived endothelial (RBE4) cells in vitro. Protein and mRNA levels of VEGF-A and FGF-2 increased after T3 stimulation of RBE4 cells. The thyroid hormone receptor blocker NH-3 abolished T3-induced Fgf2 and Vegfa upregulation, indicating a receptor-mediated effect. Thyroid hormone inhibited the apoptosis in RBE4 cells and altered mRNA levels of apoptosis-related genes, namely Bcl2 and Bad. The present results show that thyroid hormone has a substantial impact on vasculature development in the brain. Pathologically altered vascularization could, therefore, be a contributing factor to the neurologic deficits induced by thyroid hormone deficiency.
|
|
| 16. |
- Zhu, Changlian, 1964, et al.
(författare)
-
Age-dependent regenerative responses in the striatum and cortex after hypoxia-ischemia.
- 2009
-
Ingår i: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 1559-7016. ; 29:2, s. 342-54
-
Tidskriftsartikel (refereegranskat)abstract
- Regenerative responses after hypoxia-ischemia (HI) were investigated in the immature (P9) and juvenile (P21) mouse striatum and cortex by postischemic 5-bromo-2-deoxyuridine labeling and phenotyping of labeled cells 4 weeks later. HI stimulated the formation of new cells in striatum and cortex in immature, growing brains (P9), but when brain growth was finished (P21) proliferation could be stimulated only in striatum, not in cortex. However, the relative increase was higher in P21 (460%) than P9 striatum (50%), though starting from a lower level at P21. Starting from this lower level, HI-induced proliferation in P21 striatum reached the same level as in P9 striatum, but not higher. Phenotyping revealed that low levels of neurogenesis were still present in nonischemic P9 cortex and striatum, but only in striatum at P21. Ischemia-induced neurogenesis was found only in P9 striatum. Ischemia-induced gliogenesis occurred in P9 and P21 striatum as well as P9 cortex, but not in P21 cortex. Hence, the regenerative response was stronger in striatum than cortex, and stronger in P9 than P21 cortex. The biggest ischemia-induced change was the 49-fold increase in P21 striatal microglia, and this was accompanied by increased inflammation, as judged by the size and numbers of CCL2- and interleukin-18-positive cells.Journal of Cerebral Blood Flow & Metabolism advance online publication, 5 November 2008; doi:10.1038/jcbfm.2008.124.
|
|
| 17. |
- Åberg, Maria A I, 1972, et al.
(författare)
-
Cardiovascular fitness is associated with cognition in young adulthood.
- 2009
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490.
-
Tidskriftsartikel (refereegranskat)abstract
- During early adulthood, a phase in which the central nervous system displays considerable plasticity and in which important cognitive traits are shaped, the effects of exercise on cognition remain poorly understood. We performed a cohort study of all Swedish men born in 1950 through 1976 who were enlisted for military service at age 18 (N = 1,221,727). Of these, 268,496 were full-sibling pairs, 3,147 twin pairs, and 1,432 monozygotic twin pairs. Physical fitness and intelligence performance data were collected during conscription examinations and linked with other national databases for information on school achievement, socioeconomic status, and sibship. Relationships between cardiovascular fitness and intelligence at age 18 were evaluated by linear models in the total cohort and in subgroups of full-sibling pairs and twin pairs. Cardiovascular fitness, as measured by ergometer cycling, positively associated with intelligence after adjusting for relevant confounders (regression coefficient b = 0.172; 95% CI, 0.168-0.176). Similar results were obtained within monozygotic twin pairs. In contrast, muscle strength was not associated with cognitive performance. Cross-twin cross-trait analyses showed that the associations were primarily explained by individual specific, non-shared environmental influences (>/=80%), whereas heritability explained <15% of covariation. Cardiovascular fitness changes between age 15 and 18 y predicted cognitive performance at 18 y. Cox proportional-hazards models showed that cardiovascular fitness at age 18 y predicted educational achievements later in life. These data substantiate that physical exercise could be an important instrument for public health initiatives to optimize educational achievements, cognitive performance, as well as disease prevention at the society level.
|
|
| 18. |
- Åberg, Maria A I, 1972, et al.
(författare)
-
Risk factors in Swedish young men for amyotrophic lateral sclerosis in adulthood
- 2018
-
Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 265:3, s. 460-470
-
Tidskriftsartikel (refereegranskat)abstract
- Recent research suggests that the incidence of amyotrophic lateral sclerosis (ALS) may be on the rise. Since ALS becomes predominant in later life, most studies on causal factors are conducted in middle-aged or older populations where potentially important influences from early life can usually not be adequately captured. We aimed to investigate predictors in young Swedish men for ALS in adulthood. Therefore, we performed a prospective cohort study of young men (aged 16-25, n=1,819,817) who enlisted 1968-2005 and took part in comprehensive conscription examinations. Incident cases of ALS (n=526) during up to 46years of follow-up were identified in the National Hospital Register and Swedish Cause of Death Register. Those who developed ALS had lower BMI (body mass index) at conscription than their peers (p=0.03). The risk of ALS during follow-up was calculated with Cox proportional hazards models. No associations were found with physical fitness, erythrocyte sedimentation rate, or non-psychotic mental disorders. Low overall muscle strength compared to high overall muscle strength [hazard ratio (HR) 1.36; 95% confidence interval (CI) 1.01-1.83] and low BMI (a one-unit increase HR 0.96; 95% CI 0.93-0.99) and lower erythrocyte volume fraction (a one-unit increase HR 0.96; 95% CI 0.92-0.998) were the statistically significant predictors for ALS in adjusted models. These findings provide novel epidemiologic evidence of a prospective association between low overall muscle strength and erythrocyte volume fraction in young men and ALS risk.
|
|
| 19. |
- Åberg, N David, 1970, et al.
(författare)
-
Peripheral administration of GH induces cell proliferation in the brain of adult hypophysectomized rats.
- 2009
-
Ingår i: The Journal of endocrinology. - 1479-6805. ; 201:1, s. 141-50
-
Tidskriftsartikel (refereegranskat)abstract
- IGF-I treatment has been shown to enhance cell genesis in the brains of adult GH- and IGF-I-deficient rodents; however, the influence of GH therapy remains poorly understood. The present study investigated the effects of peripheral recombinant bovine GH (bGH) on cellular proliferation and survival in the neurogenic regions (subventricular zone (SVZ), and dentate gyrus of the hippocampus), as well as the corpus callosum, striatum, parietal cortex, and piriform cortex. Hypopituitarism was induced in female rats by hypophysectomy, and the rats were supplemented with thyroxine and cortisone acetate. Subsequently, the rats received daily s.c. injections of bGH for either 6 or 28 days respectively. Following 5 days of peripheral bGH administration, the number of bromodeoxyuridine (BrdU)-positive cells was increased in the hippocampus, striatum, parietal cortex, and piriform cortex after 6 and 28 days. In the SVZ, however, BrdU-positive cells increased only after 28 days of bGH treatment. No significant change was observed in the corpus callosum. In the hippocampus, after 28 days of bGH treatment, the number of BrdU/NeuN-positive cells was increased proportionally to increase the number of BrdU-positive cells. (3)H-thymidine incorporation in vitro revealed that 24 h of bGH exposure was sufficient to increase cell proliferation in adult hippocampal progenitor cells. This study shows for the first time that 1) peripheral bGH treatment increased the number of newborn cells in the adult brain and 2) bGH exerted a direct proliferative effect on neuronal progenitor cells in vitro.
|
|
| 20. |
- Adolf, A., et al.
(författare)
-
Release of astroglial vimentin by extracellular vesicles: Modulation of binding and internalization of C3 transferase in astrocytes and neurons
- 2019
-
Ingår i: Glia. - : Wiley. - 0894-1491. ; 67:4, s. 703-717
-
Tidskriftsartikel (refereegranskat)abstract
- Clostridium botulinum C3 transferase (C3bot) ADP-ribosylates rho proteins to change cellular functions in a variety of cell types including astrocytes and neurons. The intermediate filament protein vimentin as well as transmembrane integrins are involved in internalization of C3bot into cells. The exact contribution, however, of these proteins to binding of C3bot to the cell surface and subsequent cellular uptake remains to be unraveled. By comparing primary astrocyte cultures derived from wild-type with Vim(-/-) mice, we demonstrate that astrocytes lacking vimentin exhibited a delayed ADP-ribosylation of rhoA concurrent with a blunted morphological response. This functional impairment was rescued by the extracellular excess of recombinant vimentin. Binding assays using C3bot harboring a mutated integrin-binding RGD motif (C3bot-G89I) revealed the involvement of integrins in astrocyte binding of C3bot. Axonotrophic effects of C3bot are vimentin dependent and postulate an underlying mechanism entertaining a molecular cross-talk between astrocytes and neurons. We present functional evidence for astrocytic release of vimentin by exosomes using an in vitro scratch wound model. Exosomal vimentin+ particles released from wild-type astrocytes promote the interaction of C3bot with neuronal membranes. This effect vanished when culturing Vim(-/-) astrocytes. Specificity of these findings was confirmed by recombinant vimentin propagating enhanced binding of C3bot to synaptosomes from rat spinal cord and mouse brain. We hypothesize that vimentin+ exosomes released by reactive astrocytes provide a novel molecular mechanism constituting axonotrophic (neuroprotective) and plasticity augmenting effects of C3bot after spinal cord injury.
|
|
| 21. |
- Berns, E. J., et al.
(författare)
-
A tenascin-C mimetic peptide amphiphile nanofiber gel promotes neurite outgrowth and cell migration of neurosphere-derived cells
- 2016
-
Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061. ; 37, s. 50-58
-
Tidskriftsartikel (refereegranskat)abstract
- Biomimetic materials that display natural bioactive signals derived from extracellular matrix molecules like laminin and fibronectin hold promise for promoting regeneration of the nervous system. In this work, we investigated a biomimetic peptide amphiphile (PA) presenting a peptide derived from the extracellular glycoprotein tenascin-C, known to promote neurite outgrowth through interaction with beta 1 integrin. The tenascin-C mimetic PA (TN-C PA) was found to self-assemble into supramolecular nanofibers and was incorporated through co-assembly into PA gels formed by highly aligned nanofibers. TN-C PA content in these gels increased the length and number of neurites produced from neurons differentiated from encapsulated P19 cells. Furthermore, gels containing TN-C PA were found to increase migration of cells out of neurospheres cultured on gel coatings. These bioactive gels could serve as artificial matrix therapies in regions of neuronal loss to guide neural stem cells and promote through biochemical cues neurite extension after differentiation. One example of an important target would be their use as biomaterial therapies in spinal cord injury. Tenascin-C is an important extracellular matrix molecule in the nervous system and has been shown to play a role in regenerating the spinal cord after injury and guiding neural progenitor cells during brain development, however, minimal research has been reported exploring the use of biomimetic biomaterials of tenascin-C. In this work, we describe a selfassembling biomaterial system in which peptide amphiphiles present a peptide derived from tenascin-C that promotes neurite outgrowth. Encapsulation of neurons in hydrogels of aligned nanofibers formed by tenascin-C-mimetic peptide amphiphiles resulted in enhanced neurite outgrowth. Additionally, these peptide amphiphiles promoted migration of neural progenitor cells cultured on nanofiber coatings. Tenascin-C biomimetic biomaterials such as the one described here have significant potential in neuroregenerative medicine.
|
|
| 22. |
- Carlberg, Björn, 1983, et al.
(författare)
-
Electrospun polyurethane scaffolds for proliferation and neuronal differentiation of human embryonic stem cells.
- 2009
-
Ingår i: Biomedical materials (Bristol, England). - : IOP Publishing. - 1748-605X .- 1748-6041. ; 4:4
-
Tidskriftsartikel (refereegranskat)abstract
- Adult central nervous system (CNS) tissue has a limited capacity to recover after trauma or disease. Hence, tissue engineering scaffolds intended for CNS repair and rehabilitation have been subject to intense research effort. Electrospun porous scaffolds, mimicking the natural three-dimensional environment of the in vivo extracellular matrix (ECM) and providing physical support, have been identified as promising candidates for CNS tissue engineering. The present study demonstrates in vitro culturing and neuronal differentiation of human embryonic stem cells (hESCs) on electrospun fibrous polyurethane scaffolds. Electrospun scaffolds composed of biocompatible polyurethane resin (Desmopan 9370A, Bayer MaterialScience AG) were prepared with a vertical electrospinning setup. Resulting scaffolds, with a thickness of approximately 150 microm, exhibited high porosity (84%) and a bimodal pore size distribution with peaks at 5-6 and 1 microm. The mean fiber diameter was measured to approximately 360 nm with a standard deviation of 80 nm. The undifferentiated hESC line SA002 (Cellartis AB, Göteborg, Sweden) was seeded and cultured on the produced scaffolds and allowed propagation and then differentiation for up to 47 days. Cultivation of hESC on electrospun fibrous scaffolds proved successful and neuronal differentiation was observed via standard immunocytochemistry. The results indicate that predominantly dopaminergic tyrosine hydroxylase (TH) positive neurons are derived in co-culture with fibrous scaffolds, in comparison to reference cultures under the same differentiation conditions displaying large proportions of GFAP positive cell types. Scanning electron micrographs confirm neurite outgrowth and connection to adjacent cells, as well as cell attachment to individual fibers of the fibrous scaffold. Consequently, electrospun polyurethane scaffolds have been proven feasible as a substrate for hESC propagation and neuronal differentiation. The physical interaction between cells and the fibrous scaffold indicates that these scaffolds provide a three-dimensional physical structure; a potential candidate for neural tissue engineering repair and rehabilitation.
|
|
| 23. |
- Couillard-Despres, Sebastien, et al.
(författare)
-
Doublecortin expression levels in adult brain reflect neurogenesis.
- 2005
-
Ingår i: The European journal of neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 21:1, s. 1-14
-
Tidskriftsartikel (refereegranskat)abstract
- Progress in the field of neurogenesis is currently limited by the lack of tools enabling fast and quantitative analysis of neurogenesis in the adult brain. Doublecortin (DCX) has recently been used as a marker for neurogenesis. However, it was not clear whether DCX could be used to assess modulations occurring in the rate of neurogenesis in the adult mammalian central nervous system following lesioning or stimulatory factors. Using two paradigms increasing neurogenesis levels (physical activity and epileptic seizures), we demonstrate that quantification of DCX-expressing cells allows for an accurate measurement of modulations in the rate of adult neurogenesis. Importantly, we excluded induction of DCX expression during physiological or reactive gliogenesis and excluded also DCX re-expression during regenerative axonal growth. Our data validate DCX as a reliable and specific marker that reflects levels of adult neurogenesis and its modulation. We demonstrate that DCX is a valuable alternative to techniques currently used to measure the levels of neurogenesis. Importantly, in contrast to conventional techniques, analysis of neurogenesis through the detection of DCX does not require in vivo labelling of proliferating cells, thereby opening new avenues for the study of human neurogenesis under normal and pathological conditions.
|
|
| 24. |
- Devarakonda, Sravani, et al.
(författare)
-
Dietary Fiber and the Hippocampal Neurogenic Niche in a Model of Pelvic Radiotherapy
- 2021
-
Ingår i: Neuroscience. - : Elsevier BV. - 0306-4522. ; 475, s. 137-147
-
Tidskriftsartikel (refereegranskat)abstract
- sought to determine whether radiation to the colorectum had an impact on parameters of hippocampal neurogenesis and, if so, whether it could be modulated by a fiber-rich diet. Male C57BL/6J mice were fed a diet containing bioprocessed oat bran or a fiber-free diet, starting two weeks before colorectal irradiation with 4 fractions of 8 Gray or sham-irradiation. Diets were then continued for 1, 6 or 18 weeks, whereafter parameters of hippocampal neurogenesis were analyzed and correlated to serum cytokine levels. No statistically significant changes in neuronal markers or cell proliferation were found at one week post-irradiation. Six weeks postirradiation there was a decreased cell proliferation in the subgranular zone that appeared slightly more pronounced in irradiated animals on a fiber-free diet and increased numbers of immature neurons per mm2 dentate gyrus in the irradiated mice, with a statistically significant increase in mice on a fiber-rich diet. Microglial abundancy was similar between all groups. 18 weeks post-irradiation, a fiber-free diet had reduced the number of immature neurons, whereas irradiation resulted in an increase. Despite this, the population of mature neurons was stable. Analysis of serum cytokines revealed a negative correlation between MIP1-a and the number of immature neurons one week after irradiation, regardless of diet. Our findings show that pelvic radiotherapy has the potential to cause a long-lasting impact on hippocampal neurogenesis, and dietary interventions may modulate this impact. More in-depth studies on the relationship between irradiation-induced intestinal injury and brain health are warranted. (c) 2021 The Authors. Published by Elsevier Ltd on behalf of IBRO. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
|
|
| 25. |
- Diederich, Kai, et al.
(författare)
-
Synergetic effects of granulocyte-colony stimulating factor and cognitive training on spatial learning and survival of newborn hippocampal neurons.
- 2009
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:4
-
Tidskriftsartikel (refereegranskat)abstract
- Granulocyte-Colony Stimulating Factor (G-CSF) is an endogenous hematopoietic growth factor known for its role in the proliferation and differentiation of cells of the myeloic lineage. Only recently its significance in the CNS has been uncovered. G-CSF attenuates apoptosis and controls proliferation and differentiation of neural stem cells. G-CSF activates upstream kinases of the cAMP response element binding protein (CREB), which is thought to facilitate the survival of neuronal precursors and to recruit new neurons into the dentate gyrus. CREB is also essential for spatial long-term memory formation. To assess the role and the potential of this factor on learning and memory-formation we systemically administered G-CSF in rats engaged in spatial learning in an eight-arm radial maze. G-CSF significantly improved spatial learning and increased in combination with cognitive training the survival of newborn neurons in the hippocampus as measured by bromodeoxyuridine and doublecortin immunohistochemistry. Additionally, G-CSF improved re-acquisition of spatial information after 26 days. These findings support the hypothesis that G-CSF can enhance learning and memory formation. Due to its easy applicability and its history as a well-tolerated hematological drug, the use of G-CSF opens up new neurological treatment opportunities in conditions where learning and memory-formation deficits occur.
|
|
| 26. |
- Draganski, Bogdan, et al.
(författare)
-
Temporal and spatial dynamics of brain structure changes during extensive learning.
- 2006
-
Ingår i: The Journal of neuroscience : the official journal of the Society for Neuroscience. - 1529-2401. ; 26:23, s. 6314-7
-
Tidskriftsartikel (refereegranskat)abstract
- The current view regarding human long-term memory as an active process of encoding and retrieval includes a highly specific learning-induced functional plasticity in a network of multiple memory systems. Voxel-based morphometry was used to detect possible structural brain changes associated with learning. Magnetic resonance images were obtained at three different time points while medical students learned for their medical examination. During the learning period, the gray matter increased significantly in the posterior and lateral parietal cortex bilaterally. These structural changes did not change significantly toward the third scan during the semester break 3 months after the exam. The posterior hippocampus showed a different pattern over time: the initial increase in gray matter during the learning period was even more pronounced toward the third time point. These results indicate that the acquisition of a great amount of highly abstract information may be related to a particular pattern of structural gray matter changes in particular brain areas.
|
|
| 27. |
- Enejder, Annika, 1969, et al.
(författare)
-
Neuronal cell growth on polymeric scaffolds studied by CARS microscopy
- 2012
-
Ingår i: Proceedings of SPIE - Multiphoton Microscopy in the Biomedical Sciences XII, San Francisco, CA, 22-24 January 2012. - : SPIE. - 1605-7422. - 9780819488695 ; 8226
-
Konferensbidrag (refereegranskat)abstract
- For studies of neuronal cell integration and neurite outgrowth in polymeric scaffold materials as a future alternative for the treatment of damages in the neuronal system, we have developed a protocol employing CARS microscopy for imaging of neuronal networks. The benefits of CARS microscopy come here to their best use; (i) the overall three-dimensional (3D) arrangement of multiple cells and their neurites can be visualized without the need for chemical preparations or physical sectioning, potentially affecting the architecture of the soft, fragile scaffolds and (ii) details on the interaction between single cells and scaffold fibrils can be investigated by close-up images at sub-micron resolution. The establishment of biologically more relevant 3D neuronal networks in a soft hydrogel composed of native Extra Cellular Matrix (ECM) components was compared with conventional two-dimensional networks grown on a stiff substrate. Images of cells in the hydrogel scaffold reveal significantly different networking characteristics compared to the 2D networks, raising the question whether the functionality of neurons grown as layers in conventional cultivation dishes represents that of neurons in the central and peripheral nervous systems.
|
|
| 28. |
- Eriksson, Yohanna, 1982, et al.
(författare)
-
The anti-asthmatic drug, montelukast, modifies the neurogenic potential in the young healthy and irradiated brain
- 2018
-
Ingår i: Cell Death & Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 9:7
-
Tidskriftsartikel (refereegranskat)abstract
- Brain tumors are the most common form of solid tumors in children. Due to the increasing number of survivors, it is of importance to prevent long-term treatment-induced side effects. Montelukast, a leukotriene receptor antagonist, may have the desired neuroprotective properties. The aim of the study was to determine whether montelukast could reduce adverse effects of cranial irradiation (CIR) to the young brain. Daily injections of montelukast or vehicle was given to young mice for 4 or 14 days in combination with CIR or under normal conditions. Montelukast treatment for 4 days protected against cell death with 90% more cell death in the vehicle group compared to the montelukast group 24 h after CIR. It also resulted in less microglia activation 6 h after CIR, where montelukast lowered the levels of CD68 compared to the vehicle groups. Interestingly, the animals that received montelukast for 14 days had 50% less proliferating cells in the hippocampus irrespective of receiving CIR or not. Further, the total number of neurons in the granule cell layer was altered during the sub-acute phase. The number of neurons was decreased by montelukast treatment in control animals (15%), but the opposite was seen after CIR, where montelukast treatment increased the number of neurons (15%). The results show beneficial effects by montelukast treatment after CIR in some investigated parameters during both the acute phase and with longer drug treatment. However, it also resulted in lower proliferation in the hippocampus under normal conditions, indicating that the effects of montelukast can be either beneficial or unfavorable, depending on the circumstances.
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
- Hellström, Nina, 1976, et al.
(författare)
-
Differential recovery of neural stem cells in the subventricular zone and dentate gyrus after ionizing radiation.
- 2009
-
Ingår i: Stem cells (Dayton, Ohio). - : Oxford University Press (OUP). - 1549-4918 .- 1066-5099. ; 27:3, s. 634-641
-
Tidskriftsartikel (refereegranskat)abstract
- Radiation therapy is a widely used treatment for malignant CNS tumors. Mature neurons are terminally differentiated, whereas stem and progenitor cells have a prominent proliferative capacity and are therefore highly vulnerable to irradiation. Our aim was to investigate how cranial radiation in young rats would affect stem/progenitor cells in the two niches of adult neurogenesis, the subventricular zone (SVZ) and the dentate gyrus of the hippocampal formation. Nine weeks after irradiation we found that in irradiated animals, hippocampal neurogenesis was reduced to 5% of control levels. Similarly, the number of actively proliferating cells and radial glia-like stem cells (nestin+/GFAP+) in the dentate gyrus, was reduced to 10% and 15% of control levels, respectively. In the irradiated olfactory bulb, neurogenesis was reduced to 40% of control levels and the number of actively proliferating cells in the SVZ was reduced to 53% of control levels. However, the number of nestin+/GFAP+ cells in the SVZ was unchanged compared to controls. To evaluate the immediate response to the radiation injury we quantified the amount of proliferation in the SVZ and dentate gyrus one day after irradiation. We found an equal reduction in proliferating cells both in dentate gyrus and SVZ. In summary, we show an initial response to radiation injury that is similar in both brain stem cell niches. However, the long-term effects on stem cells and neurogenesis in these two areas differ significantly, where the dentate gyrus is severely affected long-term, whereas the SVZ appears to recover with time. ______________________________________________________________________________
|
|
| 33. |
|
|
| 34. |
- Hellström, Nina, 1976, et al.
(författare)
-
Unique gene expression patterns indicate microglial contribution to neural stem cell recovery following irradiation.
- 2011
-
Ingår i: Molecular and cellular neurosciences. - : Elsevier BV. - 1095-9327 .- 1044-7431. ; 46:4, s. 710-9
-
Tidskriftsartikel (refereegranskat)abstract
- Ionizing radiation results in damage to neural stem cells and reduced neurogenesis. The aim of the present study was to determine intrinsic and extrinsic factors that influence neural stem cell survival following irradiation, using qPCR. Gene expression of hippocampal and SVZ neurospheres were analyzed following irradiation, and results demonstrated that irradiated hippocampal and SVZ stem cells displayed similar gene expression profiles for intrinsic genes. Irradiated microglia (extrinsic factor) isolated from the SVZ exhibited increased gene expression of growth factors involved in stem cell maintenance, proliferation, and survival. However, microglial genes in the irradiated hippocampus responded less favorably with respect to stem cell recovery. This might explain the superior recovery of SVZ compared to hippocampal stem cells following in vivo irradiation. In addition, our results show that a combination of growth factors, which were upregulated in SVZ microglia, increased the proliferation and decreased cell death of irradiated neurospheres in vitro.
|
|
| 35. |
- Henriksson, Malin, et al.
(författare)
-
Cause-specific mortality in Swedish males diagnosed with non-psychotic mental disorders in late adolescence: a prospective population-based study.
- 2018
-
Ingår i: Journal of epidemiology and community health. - : BMJ. - 1470-2738 .- 0143-005X. ; 72:7, s. 582-8
-
Tidskriftsartikel (refereegranskat)abstract
- While risk of premature death is most pronounced among persons with severe mental illness, also milder conditions are associated with increased all-cause mortality. We examined non-psychotic mental (NPM) disorders and specific causes of natural death in a cohort of late adolescent men followed for up to 46 years.Prospective cohort study of Swedish males (n=1 784 626) who took part in structured conscription interviews 1968-2005. 74 525 men were diagnosed with NPM disorders at or prior to conscription. Median follow-up time was 26 years. HRs for cause-specific mortality were calculated using Cox proportional hazards models.Risks in fully adjusted models were particularly elevated for death by infectious diseases (depressive and neurotic/adjustment disorders (HR 2.07; 95%CI 1.60 to 2.67), personality disorders (HR 2.90; 95%CI 1.96 to 4.28) and alcohol-related and other substance use disorders (HR 9.02; 95%CI 6.63 to 12.27)) as well as by gastrointestinal causes (depressive and neurotic/adjustment disorders (HR 1.64; 95%CI 1.42 to 1.89), personality disorders (HR 2.77; 95%CI 2.27 to 3.38) and alcohol-related/substance use disorders (HR 4.41; 95%CI 3.59 to 5.42)).Young men diagnosed with NPM disorders had a long-term increased mortality risk, in particular due to infectious and gastrointestinal conditions. These findings highlight the importance of early preventive actions for adolescents with mental illness.
|
|
| 36. |
|
|
| 37. |
- Henriksson, Malin, et al.
(författare)
-
Effects of exercise on symptoms of anxiety in primary care patients: A randomized controlled trial.
- 2022
-
Ingår i: Journal of affective disorders. - : Elsevier BV. - 1573-2517 .- 0165-0327. ; 297, s. 26-34
-
Tidskriftsartikel (refereegranskat)abstract
- There is a need for high-quality research regarding exercise interventions for persons with anxiety disorders. We investigate whether a 12-week exercise intervention, with different intensities, could reduce anxiety symptoms in patients with anxiety disorders.286 patients were recruited from primary care in Sweden. Severity of symptoms was self-assessed using the Beck Anxiety Inventory (BAI) and the Montgomery Åsberg Depression Rating Scale (MADRS-S). Participants were randomly assigned to one of two group exercise programs with cardiorespiratory and resistance training and one control/standard treatment non-exercise group, with 1:1:1 allocation.Patients in both exercise groups showed larger improvements in both anxiety and depressive symptoms compared to the control group. No differences in effect sizes were found between the two groups. To study a clinically relevant improvement, BAI and MADRS-S were dichotomized with the mean change in the control group as reference. In adjusted models the odds ratio for improved symptoms of anxiety after low-intensity training was 3.62 (CI 1.34-9.76) and after moderate/high intensity 4.88 (CI 1.66-14.39), for depressive symptoms 4.96 (CI 1.81-13.6) and 4.36 (CI 1.57-12.08) respectively. There was a significant intensity trend for improvement in anxiety symptoms.The use of self-rating measures which bears the risk of an under- or overestimation of symptoms.A 12-week group exercise program proved effective for patients with anxiety syndromes in primary care. These findings strengthen the view of physical exercise as an effective treatment and could be more frequently made available in clinical practice for persons with anxiety issues.
|
|
| 38. |
- Karlsson, Lars O, 1975, et al.
(författare)
-
Constitutive PGC-1 alpha Overexpression in Skeletal Muscle Does Not Improve Morphological Outcome in Mouse Models of Brain Irradiation or Cortical Stroke
- 2018
-
Ingår i: Neuroscience. - : Elsevier BV. - 0306-4522 .- 1873-7544. ; 384, s. 314-328
-
Tidskriftsartikel (refereegranskat)abstract
- Physical exercise can improve morphological outcomes after ischemic stroke and ameliorate irradiation-induced reduction of hippocampal neurogenesis in rodents, but the mechanisms underlying these effects remain largely unknown. The transcription factor peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 alpha) is considered to be one of the central factors responsible for exercise-induced benefits in skeletal muscle, including the release of neurotrophic factors into the circulation. In order to test if PGC-1 alpha overexpression in skeletal muscle could simulate the exercise-induced effects on recovery after cranial irradiation and stroke, we used male adult transgenic mice overexpressing murine PGC-1 alpha under the control of muscle creatinine kinase promoter and subjected them to either whole brain irradiation at a dose of 4 Gy or photothrombotic stroke to the sensory motor cortex. Muscular PGC-1 alpha overexpression did not ameliorate irradiation-induced reduction of newborn BrdU-labeled cells in the dentate gyrus, immature neurons, or newborn mature neurons. In the stroke model, muscular overexpression of PGC-1 alpha resulted in an increased infarct size without any changes in microglia activation or reactive astrocytosis. No difference could be detected in the number of migrating neural progenitor cells from the subventricular zone to the lesioned neocortex or in vascular density of the contralateral neocortex in comparison to wildtype animals. We conclude that forced muscular overexpression of PGC-1 alpha does not have a beneficial effect on hippocampal neurogenesis after irradiation, but rather a detrimental effect on the infarct volume after stroke in mice. This suggests that artificial muscle activation through the PGC-1 alpha pathway is not sufficient to mimic exercise-induced recovery after cranial irradiation and stroke. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.
|
|
| 39. |
- Karlsson, Lars O, 1975, et al.
(författare)
-
Constitutive PGC-1 alpha overexpression in skeletal muscle does not protect from age-dependent decline in neurogenesis
- 2019
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Aerobic exercise prevents age-dependent decline in cognition and hippocampal neurogenesis. The transcription factor peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1 alpha) mediates many of the exercise-induced benefits in skeletal muscle, including the release of factors into the circulation with neurotrophic effects. We use a transgenic mouse model with muscle-specific overexpression of PGC-1 alpha to study the contribution of chronic muscle activation on exercise-induced effects on hippocampal neurogenesis in aging. Young and old transgenic and wild type animals of both sexes displayed a robust age-related reduction in newborn BrdU+-cells, immature neurons (DCX+-cells) and new mature BrdU(+)/NeuN(+)-neurons in the dentate gyrus. No differences were detected between genotypes or sexes. Analysis of serum proteins showed a tendency towards increased levels of myokines and reduced levels of pro-inflammatory cytokines for transgenic animals, but only musclin was found to be significantly up-regulated in transgenic animals. We conclude that constitutive muscular overexpression of PGC-1 alpha, despite potent systemic changes, is insufficient for mimicking exercise-induced effects on hippocampal neurogenesis in aging. Continued studies are required to investigate the complex molecular mechanisms by which circulating signals could mediate exercise-induced effects on the central nervous system in disease and aging, with the aim of discovering new therapeutic possibilities for patients.
|
|
| 40. |
- Karlsson, Lars O, 1975, et al.
(författare)
-
Constitutive PGC-1α Overexpression in Skeletal Muscle Does Not Contribute to Exercise-Induced Neurogenesis.
- 2021
-
Ingår i: Molecular neurobiology. - : Springer Science and Business Media LLC. - 1559-1182 .- 0893-7648. ; 58, s. 1465-1481
-
Tidskriftsartikel (refereegranskat)abstract
- Physical exercise can improve age-dependent decline in cognition, which in rodent is partly mediated by restoration of an age-dependent decline in neurogenesis. Exercise-inducible myokines in the circulation present a link in muscle-brain crosstalk. The transcription factor PGC-1α regulates the release of such myokines with neurotrophic properties into the circulation. We study how chronic muscular overexpression of PGC-1α could contribute to exercise-induced effects on hippocampal neurogenesis and if this effect could be enhanced in a running wheel paradigm. We used 3- and 11-month-old transgenic mice with overexpression of PGC-1α under the control of muscle creatinine kinase promoter (MCK-PGC-1α), which have a constitutively developed endurance muscle phenotype. Wild-type and MCK-PGC-1α mice were single housed with free access to running wheels. Four weeks of running in female animals increased the levels of newborn cells, immature neurons, and, for young animals, new mature neurons, compared to sedentary controls. However, no difference in these parameters was observed between wild-type and transgenic mice under sedentary or running conditions. Multiplex analysis of serum cytokines, chemokines, and myokines suggested several differences in serum protein concentrations between genotypes with musclin found to be significantly upregulated 4-fold in male MCK-PGC-1α animals. We conclude that constitutive muscular overexpression of PGC-1α, despite systemic changes and difference in serum composition, does not translate into exercise-induced effects on hippocampal neurogenesis, independent of the age of the animal. This suggests that chronic activation of PGC-1α in skeletal muscle is by itself not sufficient to mimic exercise-induced effects or to prevent decline of neurogenesis in aging.
|
|
| 41. |
- Kempermann, G., et al.
(författare)
-
Human Adult Neurogenesis: Evidence and Remaining Questions
- 2018
-
Ingår i: Cell Stem Cell. - : Elsevier BV. - 1934-5909 .- 1875-9777. ; 23:1, s. 25-30
-
Tidskriftsartikel (refereegranskat)abstract
- Renewed discussion about whether or not adult neurogenesis exists in the human hippocampus, and the nature and strength of the supporting evidence, has been reignited by two prominently published reports with opposite conclusions. Here, we summarize the state of the field and argue that there is currently no reason to abandon the idea that adult-generated neurons make important functional contributions to neural plasticity and cognition across the human lifespan.
|
|
| 42. |
|
|
| 43. |
- Kuhn, Hans-Georg, 1961, et al.
(författare)
-
A lifetime perspective on risk factors for cognitive decline with a special focus on early events
- 2024
-
Ingår i: CEREBRAL CIRCULATION-COGNITION AND BEHAVIOR. - 2666-2450. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Both Alzheimer's disease and vascular dementia are the result of disease processes that typically develop over several decades. Population studies have estimated that more than half of the risk for dementia is preventable or at least modifiable through behavioral adaptations. The association between these lifestyle factors and the risk of dementia is most evident for exposure in midlife. However, habits formed in middle age often reflect a lifetime of behavior patterns and living conditions. Therefore, individuals who, for example, are able to maintain healthy diets and regular exercise during their middle years are likely to benefit from these cognition-protective habits they have practiced throughout their lives. For numerous adult diseases, significant risks can often be traced back to early childhood. Suboptimal conditions during the perinatal period, childhood and adolescence can increase the risk of adult diseases, including stroke, heart disease, insulin resistance, hypertension and dementia. This review aims at summarizing some of the evidence for dementia risks from a life-time perspective with the goal of raising awareness for early dementia prevention and successful aging.
|
|
| 44. |
- Kuhn, Hans-Georg, 1961, et al.
(författare)
-
Adult Hippocampal Neurogenesis: A Coming-of-Age Story
- 2018
-
Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 38:49, s. 10401-10410
-
Tidskriftsartikel (refereegranskat)abstract
- What has become standard textbook knowledge over the last decade was a hotly debated matter a decade earlier: the proposition that new neurons are generated in the adult mammalian CNS. The early discovery by Altman and colleagues in the 1960s was vulnerable to criticism due to the lack of technical strategies for unequivocal demonstration, quantification, and physiological analysis of newly generated neurons in adult brain tissue. After several technological advancements had been made in the field, we published a paper in 1996 describing the generation of new neurons in the adult rat brain and the decline of hippocampal neurogenesis during aging. The paper coincided with the publication of several other studies that together established neurogenesis as a cellular mechanism in the adult mammalian brain. In this Progressions article, which is by no means a comprehensive review, we recount our personal view of the initial setting that led to our study and we discuss some of its implications and developments that followed. We also address questions that remain regarding the regulation and function of neurogenesis in the adult mammalian brain, in particular the existence of neurogenesis in the adult human brain.
|
|
| 45. |
|
|
| 46. |
- Kuhn, Hans-Georg, 1961
(författare)
-
Control of Cell Survival in Adult Mammalian Neurogenesis
- 2015
-
Ingår i: Cold Spring Harbor Perspectives in Biology. - : Cold Spring Harbor Laboratory. - 1943-0264. ; 7:12
-
Tidskriftsartikel (refereegranskat)abstract
- The fact that continuous proliferation of stem cells and progenitors, as well as the production of new neurons, occurs in the adult mammalian central nervous system (CNS) raises several basic questions concerning the number of neurons required in a particular system. Can we observe continued growth of brain regions that sustain neurogenesis? Or does an elimination mechanism exist to maintain a constant number of cells? If so, are old neurons replaced, or are the new neurons competing for limited network access among each other? What signals support their survival and integration and what factors are responsible for their elimination? This review will address these and other questions regarding regulatory mechanisms that control cell-death and cell-survival mechanisms during neurogenesis in the intact adult mammalian brain.
|
|
| 47. |
|
|
| 48. |
- Kuhn, Hans-Georg, 1961, et al.
(författare)
-
Detection and Phenotypic Characterization of Adult Neurogenesis
- 2016
-
Ingår i: Cold Spring Harbor Perspectives in Biology. - : Cold Spring Harbor Laboratory. - 1943-0264. ; 8:3
-
Tidskriftsartikel (refereegranskat)abstract
- Studies of adult neurogenesis have greatly expanded in the last decade, largely as a result of improved tools for detecting and quantifying neurogenesis. In this review, we summarize and critically evaluate detection methods for neurogenesis in mammalian and human brain tissue. Besides thymidine analog labeling, cell-cycle markers are discussed, as well as cell stage and lineage commitment markers. Use of these histological tools is critically evaluated in terms of their strengths and limitations, as well as possible artifacts. Finally, we discuss the method of radiocarbon dating for determining cell and tissue turnover in humans.
|
|
| 49. |
- Kuhn, Hans-Georg, 1961, et al.
(författare)
-
Developmental dysregulation of adult neurogenesis.
- 2011
-
Ingår i: The European journal of neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 33:6, s. 1115-22
-
Forskningsöversikt (refereegranskat)abstract
- Rather than a singular event that suddenly appears during adulthood, adult neurogenesis has long been recognized as the continuation of postnatal neurogenic activity. During the first postnatal weeks, significant cellular changes occur within and adjacent to germinal matrices of the subventricular zone and dentate gyrus. The majority of granule cells are generated during this period. In addition, radial glia are transformed into astrocyte-like stem cells, the ependymal layer is formed, and the highest rates of angiogenesis, gliogenesis and myelination are observed. The first postnatal weeks are critical as the brain growth rate is maximal, and changes during this period can have a great impact on neurogenesis levels and overall brain function later in life. This review chronicles cellular changes and some of the clinically relevant dysregulations that can occur during the postnatal period, and discusses the possible impact of these changes on neurogenesis and cognitive function later in life.
|
|
| 50. |
- Kuhn, Hans-Georg, 1961, et al.
(författare)
-
Increased generation of granule cells in adult Bcl-2-overexpressing mice: a role for cell death during continued hippocampal neurogenesis
- 2005
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 22:8, s. 1907-1915
-
Tidskriftsartikel (refereegranskat)abstract
- Programmed cell death is an important mechanism during brain development in order to control neuronal cell numbers and to correctly form neuronal circuitries. Programmed cell death is also present in neurogenic regions of the adult brain, and a significant portion of the adult-born cells is eliminated during the first months of maturation. We here address the question whether overexpression of the anti-apoptotic protein Bcl-2 would improve the survival of neural progenitor cells and, as a consequence, increase neurogenesis in the adult hippocampus. Transgenic animals, which express human Bcl-2 under the neuron-specific enolase promoter (NSE-huBcl-2), show a significant reduction of apoptotic cells in the hippocampal granule cell layer to about half of the wild-type level. These apoptotic cells are almost exclusively found in the zone of hippocampal progenitor activity and frequently co-label with the neuronal progenitor marker doublecortin (DCX). The rate of adult neurogenesis is doubled in the dentate gyrus of Bcl-2-overexpressing mice as demonstrated by quantification of progenitor cells using DCX and new neurons using bromodeoxyuridine (BrdU)/neuronal nuclei antigen (NeuN) double-labelling. The effect of Bcl-2 is limited to the late phase of progenitor maturation, as proliferation and early-phase progenitor cells were not affected. The increased level of neurogenesis leads to a significantly higher total number of granule cells in the dentate gyrus. These results underline the importance of developmental cell death during neurogenesis in the adult brain.
|
|
