Abstract
Previously, we have shown that chronic treatment with allopregnanolone (ALLO) for three months impaired learning function in the Swe/PS1 mouse model. ALLO is a neurosteroid, produced in the CNS and a GABAA receptor agonist. ALLO modulates the general inhibitory system in the CNS by enhancing the effect of GABA. Chronic treatment with other GABAA receptor active compounds, such as benzodiazepines, ethanol and medroxy-progesterone acetate has been associated to cognitive decline and/or increased risk for dementia. In this study, we sufficed with a treatment period of one month for the Swe/PS1 mouse, and included another Alzheimer’s disease mouse model; the Swe/Arc model. We found that one month of chronic treatment with elevated ALLO levels within physiological range impaired learning and memory function in the Swe/Arc female and male mice. Male Swe/PS1 mice also showed marginally impaired function, while the female mice did not. Furthermore, the chronic ALLO treatment caused increased levels of soluble Aβ in the Swe/PS1 mouse model while the levels were unchanged in the Swe/Arc model. Therefore, both Swe/Arc and Swe/PS1 mice showed signs of accelerated disease progression. Still, further studies are required to determine the mechanisms behind the cognitive impairment and the increased Aβ-levels caused by mildly elevated ALLO-levels.
Keywords: Allopregnanolone, Alzheimer’s disease, beta-amyloid1-42, beta-amyloid1-40, cognition, physiological stress, transgenic
Current Alzheimer Research
Title:Brief but Chronic Increase in Allopregnanolone Cause Accelerated AD Pathology Differently in Two Mouse Models
Volume: 10 Issue: 1
Author(s): Sara K. Bengtsson, Maja Johansson, Torbjorn Backstrom, Roger M. Nitsch and Mingde Wang
Affiliation:
Keywords: Allopregnanolone, Alzheimer’s disease, beta-amyloid1-42, beta-amyloid1-40, cognition, physiological stress, transgenic
Abstract: Previously, we have shown that chronic treatment with allopregnanolone (ALLO) for three months impaired learning function in the Swe/PS1 mouse model. ALLO is a neurosteroid, produced in the CNS and a GABAA receptor agonist. ALLO modulates the general inhibitory system in the CNS by enhancing the effect of GABA. Chronic treatment with other GABAA receptor active compounds, such as benzodiazepines, ethanol and medroxy-progesterone acetate has been associated to cognitive decline and/or increased risk for dementia. In this study, we sufficed with a treatment period of one month for the Swe/PS1 mouse, and included another Alzheimer’s disease mouse model; the Swe/Arc model. We found that one month of chronic treatment with elevated ALLO levels within physiological range impaired learning and memory function in the Swe/Arc female and male mice. Male Swe/PS1 mice also showed marginally impaired function, while the female mice did not. Furthermore, the chronic ALLO treatment caused increased levels of soluble Aβ in the Swe/PS1 mouse model while the levels were unchanged in the Swe/Arc model. Therefore, both Swe/Arc and Swe/PS1 mice showed signs of accelerated disease progression. Still, further studies are required to determine the mechanisms behind the cognitive impairment and the increased Aβ-levels caused by mildly elevated ALLO-levels.
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Cite this article as:
K. Bengtsson Sara, Johansson Maja, Backstrom Torbjorn, M. Nitsch Roger and Wang Mingde, Brief but Chronic Increase in Allopregnanolone Cause Accelerated AD Pathology Differently in Two Mouse Models, Current Alzheimer Research 2013; 10 (1) . https://dx.doi.org/10.2174/1567205011310010006
DOI https://dx.doi.org/10.2174/1567205011310010006 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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