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However, it is still unclear whether myelin loss is attributed to increased oligodendrocyte vulnerability, reduced repairing capacity or toxic stimuli. In the present study, we sought to clarify the starting point of myelin disruption accompanied with Oligodendrocyte Progenitor Cell (OPC) elimination in the brain of the 5xFAD mouse model of AD at 6\u2009months of age in Dentate Gyrus of the hippocampus in relation to neurotrophin system. Prominent inflammation presence was detected since the age of 6\u2009months playing a key role in myelin disturbance and AD progression. Expression analysis of neurotrophin receptors in OPCs was performed to identify new targets that could increase myelination in health and disease. OPCs in both control and 5xFAD mice express TrkB, TrkC and p75 receptors but not TrkA. Brain\u2010derived neurotrophic factor (BDNF) that binds to TrkB receptor is well\u2010known about its pro\u2010myelination effect, promoting oligodendrocytes proliferation and differentiation, so we focused our investigation on its effects in OPCs under neurodegenerative conditions. Our in vitro results showed that BDNF rescues OPCs from death and promotes their proliferation and differentiation in presence of the toxic Amyloid\u2010\u03b2 1\u201042. Collectively, our results indicate that BDNF possess an additional neuroprotective role through its actions on oligodendrocytic component and its use could be proposed as a drug\u2010based myelin\u2010enhancing strategy, complementary to amyloid and tau centered therapies in AD.<\/jats:p>","DOI":"10.1002\/glia.24505","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T10:36:22Z","timestamp":1704969382000},"page":"809-827","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Dynamics of myelin deficits in the <scp>5xFAD<\/scp> mouse model for Alzheimer's disease and the protective role of <scp>BDNF<\/scp>"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0215-5735","authenticated-orcid":false,"given":"Ioanna","family":"Zota","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Medical School University of Crete  Heraklion 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