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Long-term continuous allopregnanolone elevation causes memory decline and hippocampus shrinkage, in female wild-type B6 mice
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. Umecrine Cognit AB, Umea, Sweden.
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
2016 (engelsk)Inngår i: Hormones and Behavior, ISSN 0018-506X, E-ISSN 1095-6867, Vol. 78, s. 160-167Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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 5months, 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 1month, 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.

sted, utgiver, år, opplag, sider
2016. Vol. 78, s. 160-167
Emneord [en]
Allopregnanolone, Memory and learning, Chronic stress, Mild cognitive impairment, Dementia, Brain tissue weight, GABA, Wild-type mice, C57BL/6J mice
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URN: urn:nbn:se:umu:diva-118533DOI: 10.1016/j.yhbeh.2015.10.010ISI: 000368962200020PubMedID: 26497250OAI: oai:DiVA.org:umu-118533DiVA, id: diva2:913767
Tilgjengelig fra: 2016-03-22 Laget: 2016-03-22 Sist oppdatert: 2018-06-07bibliografisk kontrollert

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Bengtsson, Sara K SJohansson, MajaBäckström, Torbjörn

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