| 1. |
|
|
| 2. |
|
|
| 3. |
- 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.
|
|
| 4. |
- 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.
|
|
| 5. |
- 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.
|
|
| 6. |
- 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.
|
|
| 7. |
- 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.
|
|
| 8. |
- 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.
|
|
| 9. |
- 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.
|
|
| 10. |
- 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.
|
|
