Negative impact of female sex on outcomes from repetitive mild traumatic brain injury in hTau mice is age dependent: a Chronic Effects of Neurotrauma Consortium study

Ferguson, S. A. et al. (2017) Negative impact of female sex on outcomes from repetitive mild traumatic brain injury in hTau mice is age dependent: a Chronic Effects of Neurotrauma Consortium study. Frontiers in Aging Neuroscience, 9, 416. (doi:10.3389/fnagi.2017.00416) (PMID:29311903) (PMCID:PMC5744460)

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Abstract

Traumatic brain injury (TBI) is a serious public health concern which strikes someone every 15 s on average in the US. Even mild TBI, which comprise as many as 75% of all TBI cases, carries long term consequences. The effects of age and sex on long term outcome from TBI is not fully understood, but due to the increased risk for neurodegenerative diseases after TBI it is important to understand how these factors influence the outcome from TBI. This study examined the neurobehavioral and neuropathological effects of age and sex on the outcome 15 days following repetitive mild traumatic brain injury (r-mTBI) in mice transgenic for human tau (hTau). These mice express the six human isoforms of tau but do not express endogenous murine tau and they develop tau pathology and memory impairment in an age-dependent manner. After 5 mild impacts, aged female mice showed motor impairments that were absent in aged male mice, as well as younger animals. Conversely, aged female sham mice outperformed all other groups of aged mice in a Barnes maze spatial memory test. Pathologically, increases in IBA-1 and GFAP staining typically seen in this model of r-mTBI showed the expected increases with both injury and age, but phosphorylated tau stained with CP13 in the hippocampus (reduced in female sham mice compared to males) and PHF1 in the cortex (reduced in female TBI mice compared to male TBI mice) showed the only histological signs of sex-dependent differences in these mice.

Item Type:Articles
Additional Information:This material is based upon work supported by the U.S. Army Medical Research and Material Command and from the U.S. Department of Veterans Affairs [Chronic Effects of Neurotrauma Consortium] under Award No. W81XWH-13-2- 0095.
Keywords:Neuropathology, TBI, hTau, neurobehavior, tau.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Stewart, Dr William
Authors: Ferguson, S. A., Mouzon, B. C., Lynch, C., Lungmus, C., Morin, A., Crynen, G., Carper, B., Bieler, G., Mufson, E. J., Stewart, W., Mullan, M., and Crawford, F.
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Frontiers in Aging Neuroscience
Publisher:Frontiers
ISSN:1663-4365
ISSN (Online):1663-4365
Copyright Holders:Copyright © 2017 Ferguson, Mouzon, Lynch, Lungmus, Morin, Crynen, Carper, Bieler, Mufson, Stewart, Mullan and Crawford
First Published:First published in Frontiers in Aging Neuroscience 9: 416
Publisher Policy:Reproduced under a Creative Commons License

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