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- Lilja, AM, et al.
(författare)
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Neural Stem Cell Transplant-Induced Effect on Neurogenesis and Cognition in Alzheimer Tg2576 Mice Is Inhibited by Concomitant Treatment with Amyloid-Lowering or Cholinergic α7 Nicotinic Receptor Drugs
- 2015
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Ingår i: Neural plasticity. - : Hindawi Limited. - 1687-5443 .- 2090-5904. ; 2015, s. 370432-
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Tidskriftsartikel (refereegranskat)abstract
- Stimulating regeneration in the brain has the potential to rescue neuronal networks and counteract progressive pathological changes in Alzheimer’s disease (AD). This study investigated whether drugs with different mechanisms of action could enhance neurogenesis and improve cognition in mice receiving human neural stem cell (hNSC) transplants. Six- to nine-month-old AD Tg2576 mice were treated for five weeks with the amyloid-modulatory and neurotrophic drug (+)-phenserine or with the partialα7 nicotinic receptor (nAChR) agonist JN403, combined with bilateral intrahippocampal hNSC transplantation. We observed improved spatial memory in hNSC-transplanted non-drug-treated Tg2576 mice but not in those receiving drugs, and this was accompanied by an increased number of Doublecortin- (DCX-) positive cells in the dentate gyrus, a surrogate marker for newly generated neurons. Treatment with (+)-phenserine did however improve graft survival in the hippocampus. An accumulation ofα7 nAChR-expressing astrocytes was observed around the injection site, suggesting their involvement in repair and scarring processes. Interestingly, JN403 treatment decreased the number ofα7 nAChR-expressing astrocytes, correlating with a reduction in the number of DCX-positive cells in the dentate gyrus. We conclude that transplanting hNSCs enhances endogenous neurogenesis and prevents further cognitive deterioration in Tg2576 mice, while simultaneous treatments with (+)-phenserine or JN403 result in countertherapeutic effects.
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- Verkhratsky, A, et al.
(författare)
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Glial Asthenia and Functional Paralysis: A New Perspective on Neurodegeneration and Alzheimer's Disease
- 2015
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Ingår i: The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry. - : SAGE Publications. - 1089-4098. ; 21:5, s. 552-568
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Tidskriftsartikel (refereegranskat)abstract
- Neuroglia are represented by several population of cells heterogeneous in structure and function that provide for the homeostasis of the brain and the spinal cord. Neuroglial cells are also central for neuroprotection and defence of the central nervous system against exo- and endogenous insults. At the early stages of neurodegenerative diseases including Alzheimer’s disease neuroglial cells become asthenic and lose some of their homeostatic, neuroprotective, and defensive capabilities. Astroglial reactivity, for example, correlates with preservation of cognitive function in patients with mild cognitive impairment and prodromal Alzheimer’s disease. Here, we overview the experimental data indicating glial paralysis in neurodegeneration and argue that loss of glial function is fundamental for defining the progression of neurodegenerative diseases.
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