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  Female Hippocampus Vulnerability to Environmental Stress, a Precipitating Factor in Tau Aggregation Pathology

Sotiropoulos, I., Silva, J., Kimura, T., Rodrigues, A. J., Costa, P., Almeida, O. F. X., et al. (2015). Female Hippocampus Vulnerability to Environmental Stress, a Precipitating Factor in Tau Aggregation Pathology. JOURNAL OF ALZHEIMERS DISEASE, 43(3), 763-774. doi:10.3233/JAD-140693.

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 Creators:
Sotiropoulos, Ioannis1, Author
Silva, Joana1, Author
Kimura, Tetsuya1, Author
Rodrigues, Ana Joao1, Author
Costa, Patricio1, Author
Almeida, Osborne F. X.2, Author              
Sousa, Nuno1, Author
Takashima, Akihiko1, Author
Affiliations:
1external, ou_persistent22              
2Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society, ou_2035294              

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Free keywords: Chaperones, hippocampus, memory, mice, stress, tau aggregates
 Abstract: Tau-mediated neurodegeneration is a central event in Alzheimer's disease (AD) and other tauopathies. Consistent with suggestions that lifetime stress may be a clinically-relevant precipitant of AD pathology, we previously showed that stress triggers Tau hyperphosphorylation and accumulation; however, little is known about the etiopathogenic interaction of chronic stress with other AD risk factors, such as sex and aging. This study focused on how these various factors converge on the cellular mechanisms underlying Tau aggregation in the hippocampus of chronically stressed male and female (middle-aged and old) mice expressing the most commonly found disease-associated Tau mutation in humans, P301L-Tau. We report that environmental stress triggers memory impairments in female, but not male, P301L-Tau transgenic mice. Furthermore, stress elevates levels of caspase-3-truncated Tau and insoluble Tau aggregates exclusively in the female hippocampus while it also alters the expression of the molecular chaperones Hsp90, Hsp70, and Hsp105, thus favoring accumulation of Tau aggregates. Our findings provide new insights into the molecular mechanisms through which clinically-relevant precipitating factors contribute to the pathophysiology of AD. Our data point to the exquisite sensitivity of the female hippocampus to stress-triggered Tau pathology.

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Language(s): eng - English
 Dates: 2014-06-282015
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000345858000007
DOI: 10.3233/JAD-140693
 Degree: -

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Project name : Project SwitchBox
Grant ID : 259772
Funding program : Funding Programme 7 (FP7)
Funding organization : European Commission (EC)

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Title: JOURNAL OF ALZHEIMERS DISEASE
Source Genre: Journal
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Publ. Info: IOS
Pages: - Volume / Issue: 43 (3) Sequence Number: - Start / End Page: 763 - 774 Identifier: ISSN: 1387-2877