title: Tau Deletion Prevents Stress-Induced Dendritic Atrophy in Prefrontal Cortex: Role of Synaptic Mitochondria.
abstract: 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.
authors.affiliation: 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.
authors.forename: Sofia
authors.initials: S
authors.lastname: Lopes
authors.affiliation: Max Planck Institute of Psychiatry, 80804 Munich, Germany.
authors.forename: Larysa
authors.initials: L
authors.lastname: Teplytska
authors.affiliation: 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.
authors.forename: Joao
authors.initials: J
authors.lastname: Vaz-Silva
authors.affiliation: 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.
authors.forename: Chrysoula
authors.initials: C
authors.lastname: Dioli
authors.affiliation: 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.
authors.forename: Rita
authors.initials: R
authors.lastname: Trindade
authors.affiliation: 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.
authors.forename: Monica
authors.initials: M
authors.lastname: Morais
authors.affiliation: Max Planck Institute of Psychiatry, 80804 Munich, Germany.|Current address: Sandoz Biopharmaceuticals, 82041 Oberhaching, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Webhofer
authors.affiliation: Max Planck Institute of Psychiatry, 80804 Munich, Germany.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Maccarrone
authors.affiliation: Max Planck Institute of Psychiatry, 80804 Munich, Germany.
authors.forename: Osborne F X
authors.initials: OFX
authors.lastname: Almeida
authors.affiliation: Max Planck Institute of Psychiatry, 80804 Munich, Germany.
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Turck
authors.affiliation: 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.
authors.forename: Nuno
authors.initials: N
authors.lastname: Sousa
authors.affiliation: 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.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Sotiropoulos
authors.affiliation: Max Planck Institute of Psychiatry, 80804 Munich, Germany.
authors.forename: Michaela D
authors.initials: MD
authors.lastname: Filiou
mesh_terms: D000818:Animals; D001284:Atrophy; D002851:Chromatography, High Pressure Liquid; D003712:Dendrites / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000473:pathology*; D017397:Prefrontal Cortex / Q000473:pathology*; D040901:Proteomics; D013315:Stress, Psychological / Q000150:complications*; D013569:Synapses / Q000473:pathology*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins
keywords: Tau knock-out; chronic stress; dendritic atrophy; mitochondria; prefrontal cortex