proNGF Involvement in the Adult Neurogenesis Dysfunction in Alzheimer’s Disease

dc.contributor.authorOlabiyi, Bolanle Fatimat
dc.contributor.authorFleitas Pérez, Catherine
dc.contributor.authorZammou, Bahira
dc.contributor.authorFerrer, Isidre
dc.contributor.authorRampon, Claire
dc.contributor.authorEgea Navarro, Joaquim
dc.contributor.authorEspinet Mestre, Carme
dc.date.accessioned2022-07-14T08:38:13Z
dc.date.available2022-07-14T08:38:13Z
dc.date.issued2021
dc.description.abstractIn recent decades, neurogenesis in the adult brain has been well demonstrated in anumber of animal species, including humans. Interestingly, work with rodents has shown that adultneurogenesis in the dentate gyrus (DG) of the hippocampus is vital for some cognitive aspects, asincreasing neurogenesis improves memory, while its disruption triggers the opposite effect. Adultneurogenesis declines with age and has been suggested to play a role in impaired progressive learningand memory loss seen in Alzheimer’s disease (AD). Therefore, therapeutic strategies designed toboost adult hippocampal neurogenesis may be beneficial for the treatment of AD. The precursor formsof neurotrophins, such as pro-NGF, display remarkable increase during AD in the hippocampusand entorhinal cortex. In contrast to mature NGF, pro-NGF exerts adverse functions in survival,proliferation, and differentiation. Hence, we hypothesized that pro-NGF and its p75 neurotrophinreceptor (p75NTR) contribute to disrupting adult hippocampal neurogenesis during AD. To test thishypothesis, in this study, we took advantage of the availability of mouse models of AD (APP/PS1),which display memory impairment, and AD human samples to address the role of pro-NGF/p75NTRsignaling in different aspects of adult neurogenesis. First, we observed that DG doublecortin (DCX) +progenitors express p75NTR both, in healthy humans and control animals, although the percentageof DCX+ cells are significantly reduced in AD. Interestingly, the expression of p75NTR in theseprogenitors is significantly decreased in AD conditions compared to controls. In order to assessthe contribution of the pro-NGF/p75NTR pathway to the memory deficits of APP/PS1 mice, weinjected pro-NGF neutralizing antibodies (anti-proNGF) into the DG of control and APP/PS1 miceand animals are subjected to a Morris water maze test. Intriguingly, we observed that anti-pro-NGF significantly restored memory performance of APP/PS1 animals and significantly increasethe percentage of DCX+ progenitors in the DG region of these animals. In summary, our resultssuggest that pro-NGF is involved in disrupting spatial memory in AD, at least in part by blockingadult neurogenesis. Moreover, we propose that adult neurogenesis alteration should be taken intoconsideration for better understanding of AD pathology. Additionally, we provide a new molecularentry point (pro-NGF/p75NTR signaling) as a promising therapeutic target in AD.ca_ES
dc.description.sponsorshipThis work was supported by “Fundació La Marató 2015” (C.E.). We thank, IRB Lleida Biobank (B.0000682), PLATAFORMA BIOBANCOS PT13/0010/0014, HUB-ICO-IDIBELL Biobankfor providing human tissue, and UAI IRBLleida for management supportca_ES
dc.identifier.doihttps://doi.org/10.3390/ijms221910744
dc.identifier.idgrec032217
dc.identifier.issn1422-0067
dc.identifier.urihttp://hdl.handle.net/10459.1/83631
dc.language.isoengca_ES
dc.publisherMDPIca_ES
dc.relation.isformatofReproducció del document publicat a: https://doi.org/10.3390/ijms221910744 ca_ES
dc.relation.ispartofInternational Journal of Molecular Sciences, 2021, vol. 22, núm. 19ca_ES
dc.rightscc-by (c) Authors, 2021ca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectAlzheimer’s diseaseca_ES
dc.subjectAdult neurogenesisca_ES
dc.subjectpro-NGFca_ES
dc.subjectp75ca_ES
dc.subjectDentate gyrusca_ES
dc.subjectMemory impairmentca_ES
dc.titleproNGF Involvement in the Adult Neurogenesis Dysfunction in Alzheimer’s Diseaseca_ES
dc.typeinfo:eu-repo/semantics/articleca_ES
dc.type.versioninfo:eu-repo/semantics/publishedVersionca_ES
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