Tau Deletion Prevents Stress-Induced Dendritic Atrophy in Prefrontal Cortex: Role of Synaptic Mitochondria.

Autor:	Lopes S; Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal.; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães 4710-057, Portugal., Teplytska L; Max Planck Institute of Psychiatry, 80804 Munich, Germany., Vaz-Silva J; Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal.; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães 4710-057, Portugal., Dioli C; Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal.; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães 4710-057, Portugal., Trindade R; Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal.; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães 4710-057, Portugal., Morais M; Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal.; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães 4710-057, Portugal., Webhofer C; Max Planck Institute of Psychiatry, 80804 Munich, Germany.; Current address: Sandoz Biopharmaceuticals, 82041 Oberhaching, Germany., Maccarrone G; Max Planck Institute of Psychiatry, 80804 Munich, Germany., Almeida OFX; Max Planck Institute of Psychiatry, 80804 Munich, Germany., Turck CW; Max Planck Institute of Psychiatry, 80804 Munich, Germany., Sousa N; Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal.; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães 4710-057, Portugal., Sotiropoulos I; Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal.; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães 4710-057, Portugal., Filiou MD; Max Planck Institute of Psychiatry, 80804 Munich, Germany.
Jazyk:	angličtina
Zdroj:	Cerebral cortex (New York, N.Y. : 1991) [Cereb Cortex] 2017 Apr 01; Vol. 27 (4), pp. 2580-2591.
DOI:	10.1093/cercor/bhw057
Abstrakt:	Tau protein in dendrites and synapses has been recently implicated in synaptic degeneration and neuronal malfunction. Chronic stress, a well-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 as well 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. (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu