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  Chronic Allopregnanolone Treatment Accelerates Alzheimer's Disease Development in AβPPSwePSEN1ΔE9 Mice
 
 
Titel: Chronic Allopregnanolone Treatment Accelerates Alzheimer's Disease Development in AβPPSwePSEN1ΔE9 Mice
Auteur: Bengtsson, Sara K.
Johansson, Maja
Bäckström, Torbjörn
Wang, Mingde
Verschenen in: Journal of Alzheimer's disease
Paginering: Jaargang 31 (2012) nr. 1 pagina's 71-84
Jaar: 2012-04-10
Inhoud: The endogenous neurosteroid allopregnanolone alters neuronal excitability via modulation of the GABAA receptor and causes decreased neurotransmission. In Alzheimer's disease (AD), neurotransmission seems to alter the levels of toxic intracellular amyloid-β (Aβ) oligomers, which are implicated in AD pathogenesis and cause cognitive decline. Inhibition of synaptic activity has been shown to increase levels of intracellular Aβ. Allopregnanolone at endogenous stress levels inhibits synaptic activity and could have similar effects. By using a transgenic AβPPSwePSEN1ΔE9 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 Aβ 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.
Uitgever: IOS Press
Bronbestand: Elektronische Wetenschappelijke Tijdschriften
 
 

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