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Chronic Allopregnan...
Chronic Allopregnanolone Treatment Accelerates Alzheimer's Disease Development in A beta PP(Swe)PSEN1(Delta E9) Mice
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- Bengtsson, Sara K. (författare)
- Umeå universitet,Obstetrik och gynekologi
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- Johansson, Maja (författare)
- Umeå universitet,Obstetrik och gynekologi
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- Bäckström, Torbjörn (författare)
- Umeå universitet,Obstetrik och gynekologi
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- Wang, Mingde (författare)
- Umeå universitet,Obstetrik och gynekologi
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(creator_code:org_t)
- 2012
- 2012
- Engelska.
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 31:1, s. 71-84
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- The endogenous neurosteroid allopregnanolone alters neuronal excitability via modulation of the GABA(A) receptor and causes decreased neurotransmission. In Alzheimer's disease (AD), neurotransmission seems to alter the levels of toxic intracellular amyloid-beta (A beta) oligomers, which are implicated in AD pathogenesis and cause cognitive decline. Inhibition of synaptic activity has been shown to increase levels of intracellular A beta. Allopregnanolone at endogenous stress levels inhibits synaptic activity and could have similar effects. By using a transgenic A beta PP(Swe)PSEN1(Delta E9) mouse model for AD, we observed that chronic allopregnanolone treatment for three months with stress levels of allopregnanolone impaired learning in the Morris water maze. The learning impairment was seen one month after the end of treatment. Chronic allopregnanolone treatment also led to increased levels of soluble A beta in the brain, which could be a sign of advanced pathogenesis. Since the learning and memory of wild-type mice was not affected by the treatment, we propose that chronic allopregnanolone treatment accelerates the pathogenesis of AD. However, further studies are required in order to determine the underlying mechanism.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Allopregnanolone
- Alzheimer's disease
- amyloid-beta
- amyloid-beta(1-40)
- amyloid-beta(1-42)
- cognition
- physiological stress
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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