| 31. |
- Hebsgaard, Josephine, et al.
(författare)
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Strengths and limitations of the neurosphere culture system.
- 2006
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Ingår i: Molecular Neurobiology. - 1559-1182. ; 34:3, s. 153-161
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Tidskriftsartikel (refereegranskat)abstract
- After the initial reports of free-floating cultures of neural stem cells termed neurospheres (1,2), a wide array of studies using this promising culture system emerged. In theory, this was a near-perfect system for large-scale production of neural cells for use in cell replacement therapies and to assay for and characterize neural stem cells. More than a decade later, after rigorous scrutiny and ample experimental testing of the neurosphere culture system, it has become apparent that the culture system suffers from several disadvantages, and its usefulness is limited for several applications. Nevertheless, the bulk of high-quality research produced over the last decade has also shown that under the right circumstances and for the appropriate purposes, neurospheres hold up to their initial promise. This article discusses the pros and cons of the neurosphere culture system regarding its three major applications: as an assay for neural stem cells, as a model system for neurogenesis and neural development, and for expansion of neural stem cells for transplantation purposes.
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| 32. |
- Heiss, Christina, et al.
(författare)
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MyD88 Deficiency, but Not Gut Microbiota Depletion, Is Sufficient to Modulate the Blood-Brain Barrier Function in the Mediobasal Hypothalamus
- 2022
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Ingår i: Molecular Neurobiology. - : Springer Science and Business Media LLC. - 0893-7648 .- 1559-1182. ; 59:6, s. 3755-3766
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Tidskriftsartikel (refereegranskat)abstract
- Circumventricular organs (CVOs), including the mediobasal hypothalamus (MBH), have an incomplete blood-brain barrier (BBB). In this study, we determined if the BBB function in the MBH is modulated by the gut microbiota or by the Toll-like receptor (TLR) adapter proteins TRIF or MyD88 signaling. By injecting mice with Evans blue, a marker for BBB permeability, we show that germ-free (GF) and conventionally raised (CONV-R) mice did not differ in the number of Evans blue-positive cells in MBH. Acute modulation of the gut microbiota did not change the number of Evans blue-positive cells. In contrast, CONV-R Myd88(-/-) and Trif(-/-) mice had a reduced number of cells in direct contact to the circulation compared to wildtype (WT) mice. This was accompanied by increased tight junction proteins in the blood vessels in Myd88(-/-) mice. To further characterize the BBB function, we injected WT and Myd88 (-/-) CONV-R mice as well as WT GF mice with monosodium glutamate (MSG), a neurotoxin that does not cross the BBB. While MSG caused vast cell death in the MBH in CONV-R and GF WT mice, Myd88 (-/-) mice were protected from such cell death suggesting that fewer cells are exposed to the neurotoxin in the Myd88 (-/-) mice. Taken together, our results suggest that MyD88 deficiency, but not gut microbiota depletion, is sufficient to modulate the BBB function in the MBH.
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| 33. |
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| 34. |
- Karlsson, Lars O, 1975, et al.
(författare)
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Constitutive PGC-1α Overexpression in Skeletal Muscle Does Not Contribute to Exercise-Induced Neurogenesis.
- 2021
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Ingår i: Molecular neurobiology. - : Springer Science and Business Media LLC. - 1559-1182 .- 0893-7648. ; 58, s. 1465-1481
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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.
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| 35. |
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| 36. |
- Larsson, Max
(författare)
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Ionotropic glutamate receptors in spinal nociceptive processing.
- 2009
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Ingår i: Molecular Neurobiology. - : Springer. - 0893-7648 .- 1559-1182. ; 40:3, s. 260-288
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Tidskriftsartikel (refereegranskat)abstract
- Glutamate is the predominant excitatory transmitter used by primary afferent synapses and intrinsic neurons in the spinal cord dorsal horn. Accordingly, ionotropic glutamate receptors mediate basal spinal transmission of sensory, including nociceptive, information that is relayed to supraspinal centers. However, it has become gradually more evident that these receptors are also crucially involved in short- and long-term plasticity of spinal nociceptive transmission, and that such plasticity have an important role in the pain hypersensitivity that may result from tissue or nerve injury. This review will cover recent findings on pre- and postsynaptic regulation of synaptic function by ionotropic glutamate receptors in the dorsal horn and how such mechanisms contribute to acute and chronic pain.
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| 37. |
- Lema Tomé, Carla, et al.
(författare)
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Inflammation and α-Synuclein's Prion-like Behavior in Parkinson's Disease-Is There a Link?
- 2013
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Ingår i: Molecular Neurobiology. - : Springer Science and Business Media LLC. - 1559-1182 .- 0893-7648. ; 47:2, s. 561-574
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Forskningsöversikt (refereegranskat)abstract
- Parkinson's disease patients exhibit progressive spreading of aggregated α-synuclein in the nervous system. This slow process follows a specific pattern in an inflamed tissue environment. Recent research suggests that prion-like mechanisms contribute to the propagation of α-synuclein pathology. Little is known about factors that might affect the prion-like behavior of misfolded α-synuclein. In this review, we suggest that neuroinflammation plays an important role. We discuss causes of inflammation in the olfactory bulb and gastrointestinal tract and how this may promote the initial misfolding and aggregation of α-synuclein, which might set in motion events that lead to Parkinson's disease neuropathology. We propose that neuroinflammation promotes the prion-like behavior of α-synuclein and that novel anti-inflammatory therapies targeting this mechanism could slow disease progression.
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| 38. |
- Levi-Montalcini, R, et al.
(författare)
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Rita's 102!!
- 2011
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Ingår i: Molecular neurobiology. - 1559-1182. ; 43:2, s. 77-79
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 39. |
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| 40. |
- Li, Tao, et al.
(författare)
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AIF Overexpression Aggravates Oxidative Stress in Neonatal Male Mice After Hypoxia-Ischemia Injury
- 2022
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Ingår i: Molecular Neurobiology. - : Springer Science and Business Media LLC. - 0893-7648 .- 1559-1182. ; 59:11, s. 6613-6631
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Tidskriftsartikel (refereegranskat)abstract
- There are sex differences in the severity, mechanisms, and outcomes of neonatal hypoxia-ischemia (HI) brain injury, and apoptosis-inducing factor (AIF) may play a critical role in this discrepancy. Based on previous findings that AIF over-expression aggravates neonatal HI brain injury, we further investigated potential sex differences in the severity and molecular mechanisms underlying the injury using mice that overexpress AIF from homozygous transgenes. We found that the male sex significantly aggravated AIF-driven brain damage, as indicated by the injury volume in the gray matter (2.25 times greater in males) and by the lost volume of subcortical white matter (1.71 greater in males) after HI. As compared to females, male mice exhibited more severe brain injury, correlating with reduced antioxidant capacities, more pronounced protein carbonylation and nitration, and increased neuronal cell death. Under physiological conditions (without HI), the doublecortin-positive area in the dentate gyrus of females was 1.15 times larger than in males, indicating that AIF upregulation effectively promoted neurogenesis in females in the long term. We also found that AIF stimulated carbohydrate metabolism in young males. Altogether, these findings corroborate earlier studies and further demonstrate that AIF is involved in oxidative stress, which contributes to the sex-specific differences observed in neonatal HI brain injury.
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