PMID- 28555078 OWN - NLM STAT- MEDLINE DCOM- 20171113 LR - 20220331 IS - 1476-5578 (Electronic) IS - 1359-4184 (Linking) VI - 22 IP - 8 DP - 2017 Aug TI - Tau-dependent suppression of adult neurogenesis in the stressed hippocampus. PG - 1110-1118 LID - 10.1038/mp.2017.103 [doi] AB - 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-3beta (GSK3beta)/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. FAU - Dioli, C AU - Dioli C AD - Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal. AD - ICVS/3B's-PT Government Associate Laboratory, Braga/Guimaraes, Portugal. FAU - Patricio, P AU - Patricio P AD - Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal. AD - ICVS/3B's-PT Government Associate Laboratory, Braga/Guimaraes, Portugal. FAU - Trindade, R AU - Trindade R AD - Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal. AD - ICVS/3B's-PT Government Associate Laboratory, Braga/Guimaraes, Portugal. FAU - Pinto, L G AU - Pinto LG AD - Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal. AD - ICVS/3B's-PT Government Associate Laboratory, Braga/Guimaraes, Portugal. FAU - Silva, J M AU - Silva JM AD - Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal. AD - ICVS/3B's-PT Government Associate Laboratory, Braga/Guimaraes, Portugal. FAU - Morais, M AU - Morais M AD - Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal. AD - ICVS/3B's-PT Government Associate Laboratory, Braga/Guimaraes, Portugal. FAU - Ferreiro, E AU - Ferreiro E AD - Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal. AD - Institute for Interdisciplinary Research of the University of Coimbra (IIIUC), Coimbra, Portugal. FAU - Borges, S AU - Borges S AD - Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal. AD - ICVS/3B's-PT Government Associate Laboratory, Braga/Guimaraes, Portugal. FAU - Mateus-Pinheiro, A AU - Mateus-Pinheiro A AD - Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal. AD - ICVS/3B's-PT Government Associate Laboratory, Braga/Guimaraes, Portugal. FAU - Rodrigues, A J AU - Rodrigues AJ AD - Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal. AD - ICVS/3B's-PT Government Associate Laboratory, Braga/Guimaraes, Portugal. FAU - Sousa, N AU - Sousa N AD - Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal. AD - ICVS/3B's-PT Government Associate Laboratory, Braga/Guimaraes, Portugal. FAU - Bessa, J M AU - Bessa JM AD - Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal. AD - ICVS/3B's-PT Government Associate Laboratory, Braga/Guimaraes, Portugal. FAU - Pinto, L AU - Pinto L AD - Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal. AD - ICVS/3B's-PT Government Associate Laboratory, Braga/Guimaraes, Portugal. FAU - Sotiropoulos, I AU - Sotiropoulos I AD - Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal. AD - ICVS/3B's-PT Government Associate Laboratory, Braga/Guimaraes, Portugal. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170530 PL - England TA - Mol Psychiatry JT - Molecular psychiatry JID - 9607835 RN - 0 (beta Catenin) RN - 0 (tau Proteins) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.26 (Glycogen Synthase Kinase 3) SB - IM MH - Animals MH - Astrocytes/metabolism MH - Cell Proliferation MH - Cell Survival MH - Dentate Gyrus/metabolism MH - Disease Models, Animal MH - Glycogen Synthase Kinase 3/metabolism MH - Hippocampus/metabolism MH - Male MH - Mice MH - Neurogenesis/*physiology MH - Neuronal Plasticity/physiology MH - Neurons/metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - Phosphorylation MH - Signal Transduction MH - Stress, Physiological MH - beta Catenin/metabolism MH - tau Proteins/*metabolism EDAT- 2017/05/31 06:00 MHDA- 2017/11/14 06:00 CRDT- 2017/05/31 06:00 PHST- 2016/05/23 00:00 [received] PHST- 2017/03/21 00:00 [revised] PHST- 2017/03/28 00:00 [accepted] PHST- 2017/05/31 06:00 [pubmed] PHST- 2017/11/14 06:00 [medline] PHST- 2017/05/31 06:00 [entrez] AID - mp2017103 [pii] AID - 10.1038/mp.2017.103 [doi] PST - ppublish SO - Mol Psychiatry. 2017 Aug;22(8):1110-1118. doi: 10.1038/mp.2017.103. Epub 2017 May 30.