Autor(es): Dioli, Chrysoula ; Patrício, P. ; Trindade, R. ; Pinto, L. G. ; Silva, J. M. ; Morais, M. ; Ferreiro, E. ; Borges, S. ; Mateus-Pinheiro, A. ; Rodrigues, A. J. ; Sousa, Nuno ; Peixoto, João Miguel Seiça Bessa ; Pinto, Luísa ; Sotiropoulos, I.
Data: 2017
Identificador Persistente: https://hdl.handle.net/1822/51555
Origem: RepositóriUM - Universidade do Minho
Stress, a well-known sculptor of brain plasticity, is shown to suppress hippocampal neurogenesis in the adult brain; yet, the underlying cellular mechanisms are poorly investigated. Previous studies have shown that chronic stress triggers hyperphosphorylation and accumulation of the cytoskeletal protein Tau, a process that may impair the cytoskeleton-regulating role (s) of this protein with impact on neuronal function. Here, we analyzed the role of Tau on stress-driven suppression of neurogenesis in the adult dentate gyrus (DG) using animals lacking Tau (Tau-knockout; Tau-KO) and wild-type (WT) littermates. Unlike WTs, Tau-KO animals exposed to chronic stress did not exhibit reduction in DG proliferating cells, neuroblasts and newborn neurons; however, newborn astrocytes were similarly decreased in both Tau-KO and WT mice. In addition, chronic stress reduced phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR)/glycogen synthase kinase-3 beta (GSK3 beta)/beta-catenin signaling, known to regulate cell survival and proliferation, in the DG of WT, but not Tau-KO, animals. These data establish Tau as a critical regulator of the cellular cascades underlying stress deficits on hippocampal neurogenesis in the adult brain.
