Increased neurogenesis in young transgenic mice overexpressing human APP(Sw, Ind).
APP overexpressing mice have been widely used in the study of Alzheimer's disease (AD), focusing mainly at older ages, with higher accumulation of amyloid-beta peptide (Abeta). A decrease in hippocampal adult neurogenesis has been described in these models and proposed to be a consequence of Abeta accumulation. Only one study demonstrates increased neurogenesis in the hippocampus of APP-overexpressing J20 mice, and suggests it is a compensatory effect due to a subtle Abeta-induced damage. We have previously reported that a specific aggregation of Abeta has neurogenic potential on neural stem cells (NSC) in vitro. In order to clarify the contradicting data reported in vivo, we investigated NSC proliferation and neuronal differentiation in the hippocampi of J20 mice at a broader range of ages. Using immunohistochemistry, we show increased proliferation and neuronal differentiation in the hippocampi of 3 month-old J20 mice that reverted when animals became older. The increase in neurogenesis correlated with detectable levels of oligomeric Abeta, measured by ELISA and western blot. We suggest that oligomeric Abeta directly induces neurogenesis in vivo as has been demonstrated in vitro. Understanding the mechanisms underlying these changes could lead to treatments to control the neuronal differentiation of endogenous precursors through the progress of AD.
López-Toledano
Miguel A
MA
Taub Institute for Research on Alzheimer's disease and the Aging Brain and Department of Pathology, Columbia University, New York, NY 10032, USA. miguel.lopeztoledano@uca.es
Shelanski
Michael L
ML
D000367:Age Factors; D000544:Alzheimer Disease / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D039842:Neural Cell Adhesion Molecule L1 / Q000276:immunology; D009474:Neurons / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012794:Sialic Acids / Q000276:immunology
D016564:Amyloid beta-Protein Precursor; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D039842:Neural Cell Adhesion Molecule L1; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule