Journal
HORMONES AND BEHAVIOR
Volume 78, Issue -, Pages 160-167Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.yhbeh.2015.10.010
Keywords
Allopregnanolone; Memory and learning; Chronic stress; Mild cognitive impairment; Dementia; Brain tissue weight; GABA; Wild-type mice; C57BL/6J mice
Categories
Funding
- Umed University
- Umecrine Cognition AB
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Chronic stress in various forms increases the risk for cognitive dysfunction, dementia and Alzheimer's disease. While the pathogenesis behind these findings is unknown, growing evidence suggests that chronic increase in neurosteroid levels, such as allopregnanolone, is part of the mechanism. We treated wild-type C57BL/6J mice with allopregnanolone for 5 months, using osmotic pumps. This treatment led to moderately increased levels of allopregnanolone, equivalent to that of mild chronic stress. After an interval of no treatment for 1 month, female mice showed impaired learning and memory function in the Morris water maze (MWM) in combination with diminished hippocampus weight and increased cerebellum weight, both correlating to MWM performance. Male mice showed a minor reduction in memory function and no differences in brain structure. We conclude that chronic allopregnanolone elevation can lead to cognitive dysfunction and negative brain alterations. We suggest that allopregnanolone could play a key role in the pathogenesis of stress-induced cognitive disturbances and perhaps dementia. (C) 2015 Elsevier Inc. All rights reserved.
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