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|Title:||Tau-dependent suppression of adult neurogenesis in the stressed hippocampus|
Pinto, L. G.
Silva, J. M.
Rodrigues, A. J.
Peixoto, João Miguel Seiça Bessa
|Publisher:||Nature Publishing Group|
|Citation:||Dioli, C., Patrício, P., Trindade, R., Pinto, L. G., Silva, J. M., Morais, M., ... & Sousa, N. (2017). Tau-dependent suppression of adult neurogenesis in the stressed hippocampus. Molecular psychiatry, 22(8), 1110|
|Abstract(s):||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.|
|Appears in Collections:||ICVS - Artigos em Revistas Internacionais com Referee|