Author(s):
Lopes, Sofia Oliveira ; Teplytska, Larysa ; Silva, João Luís Vaz Lima da ; Dioli, Chrysoula ; Trindade, Rita ; Morais, Mónica ; Webhofer, Christian ; Maccarrone, Guiseppina ; Almeida, Osborne ; Turck, Christoph ; Sousa, Nuno ; Sotiropoulos, I. ; Filiou, Michaela
Date: 2017
Persistent ID: http://hdl.handle.net/1822/46258
Origin: RepositóriUM - Universidade do Minho
Project/scholarship:
info:eu-repo/grantAgreement/FCT/PD/PD%2FBD%2F105938%2F2014/PT;
info:eu-repo/grantAgreement/EC/FP7/259772/EU;
info:eu-repo/grantAgreement/FCT/5876-PPCDTI/113934/PT
;
Subject(s): Chronic stress; Dendritic atrophy; Mitochondria; Prefrontal cortex; Tau knock-out; Science & Technology
Description
Tau protein in dendrites and synapses has been recently implicated in synaptic degeneration and neuronal malfunction. Chronic stress, awell-known inducer of neuronal/synaptic atrophy, triggers hyperphosphorylation of Tau protein and cognitive deficits. However, the cause–effect relationship between these events remains to be established. To test the involvement of Tau in stress-induced impairments of cognition,we investigated the impact of stress on cognitive behavior, neuronal structure, and the synaptic proteome in the prefrontal cortex (PFC) of Tau knock-out (Tau-KO) and wild-type (WT) mice. Whereas exposure to chronic stress resulted in atrophy of apical dendrites and spine loss in PFC neurons as well as significant impairments in working memory in WT mice, such changes were absent in Tau-KO animals. Quantitative proteomic analysis of PFC synaptosomal fractions, combined with transmission electron microscopy analysis, suggested a prominent role for mitochondria in the regulation of the effects of stress. Specifically, chronically stressed animals exhibit Tau-dependent alterations in the levels of proteins involved in mitochondrial transport and oxidative phosphorylation aswell as in the synaptic localization of mitochondria in PFC. These findings provide evidence for a causal role of Tau in mediating stress-elicited neuronal atrophy and cognitive impairment and indicate that Tau may exert its effects through synaptic mitochondria.
This work was funded by the Portuguese Foundation for Science & Technology (FCT, grant number NMC-113934 to I.S.), the EU Consortium Switchbox (grant number Health-FP7-2010-259772 to O.F.X.A. and N.S.), the Deutsche Forschungsgemeinschaft (grant number FI 1895/1-1 to M.D.F.) and the Max Planck Society (M.D.F., G.M., C.W.T., and O.F.X.A.). In addition, this workwas also co-financed by the Portuguese North Regional Operational Program (ON.2 – O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER) (N.S.). S.L. and I.S. are holders of FCT Fellowships. J.V-S. is a recipient of a PhD fellowship (PD/ BD/105938/2014) of the University of Minho MD/PhD Program funded by FCT.
info:eu-repo/semantics/publishedVersion
