Chronic allopregnanolone elevation cause altered plaque production in Swe/PS1 mice
(English)Manuscript (preprint) (Other academic)
Abstract. We have previously shown that chronic elevation of the neurosteroid allopregnanolone caused learning dysfunction and increased levels of soluble Aβ in the Swe/PS1 mouse model. The mechanism behind these findings is however unknown. We further investigated the brain tissue of these mice to identify any effects on congophilic plaque burden, Aβ42-specific plaque burden and synaptic function. We found a significant reduction in the average size of the congophilic core of neuritic plaques after chronic allopregnanolone treatment compared to vehicle. This seems to be caused by an altered plaque production, leading to more abundant, but smaller neuritic plaques. We may also have detected a decrease in the amount of synaptophysin, and thus synaptic function among the same mice. However, the long interval between the end of treatment and tissue collection possibly allowed time for recovery and only minor differences were noted. We found that the natural relationship between levels of insoluble Aβ, congophilic and Aβ42-specific plaque load was disrupted after chronically elevated allopregnanolone levels. Furthermore, the levels of syn-aptophysin and insoluble Aβ became more important in the relationship to learning and memory. The causality of these factors is still unknown and further studies are required to fully understand the effect of neurosteroids on AD development.
Alzheimer's disease, allopregnanolone, neuroendocrinology, GABA, beta-amyloid, synaptophysin, chronic stress
Research subject Obstetrics and Gynaecology; Medical Pharmacology; medicinsk beteendevetenskap; Neurology
IdentifiersURN: urn:nbn:se:umu:diva-66574OAI: oai:DiVA.org:umu-66574DiVA: diva2:608562
FunderSwedish Research Council, 4x-11198