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O3–13–02: Chronic treatment with a CNTF‐derived peptide reverses dendritic and synaptic plasticity deficits, cognitive impairment and tau pathology in an Alzheimer's disease mouse model
- Source :
- Alzheimer's & Dementia. 9
- Publication Year :
- 2013
- Publisher :
- Wiley, 2013.
-
Abstract
- suggested to impair hippocampal neurogenesis, which can be linked to cognitive decline in aging and AD. The a 7 nAChRs play an important role in modulating synaptic plasticity in the hippocampus and we have previously reported an increased expression of a 7 nAChRs on reactive astrocytes in AD postmortem brain (Yu et al., 2005). Here we propose that stimulating a 7 nAChR signaling induces a favorable brain microenvironment, which could enhance repair processes and ameliorate cognitive impairment. Methods: Different aspects of neuroinflammation in relation to AD pathogenesis were investigated. i) First, human microglia cells were exposed to beta-amyloid 42 at nM concentrations and we studied how the secretion of pro-inflammatory cytokines released in cell media affected human stem cell neuronal differentiation in vitro. ii) Later, to evaluate astroglial processes in relation to neurogenesis in vivo, we used AD Tg2576 mice, which were treated with daily i.p. injections for 5 weeks with the partial a 7 nAChR agonist JN403 (0.03 mg/kg) in combination with bilateral human neural stem cell (hNSC) transplantation in the hippocampus. Results: Surprisingly, microglia exposed to fibrillary beta-amyloid 42, decreased secretion of cytokines TNF a, IL-1 band IL-2, which in turn impaired human stem cells differentiation(p
- Subjects :
- Microglia
Epidemiology
Health Policy
Neurogenesis
Biology
Hippocampal formation
Neural stem cell
Psychiatry and Mental health
Cellular and Molecular Neuroscience
medicine.anatomical_structure
nervous system
Developmental Neuroscience
Synaptic plasticity
medicine
Neurology (clinical)
Geriatrics and Gerontology
Stem cell
Cognitive decline
Neuroscience
Neuroinflammation
Subjects
Details
- ISSN :
- 15525279 and 15525260
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Alzheimer's & Dementia
- Accession number :
- edsair.doi...........156b9d502ae6c549db4e4f8640ff16f7