Amyloid-β oligomer dependent modulation of gastrointestinal contractility

: implications for dysmotility in Alzheimer’s Disease

Abstract

At the outset of my PhD, my broad aims were to first characterise the expression of APP within the enteric nervous system (ENS) of wild-type (WT) animals, using immunohistochemistry (IHC). Following this, I then set out to characterise the expression of Aβ within the ENS of a transgenic model displaying an overexpression of amyloid precursor protein (APP) and subsequent increase in Aβ (APP-PSEN1 model). I then endeavoured to determine whether Alzheimer’s disease (AD) pathology, namely amyloid-β (Aβ), alters the expression of key neurotransmitter and inflammatory systems within the ENS, using the APP-PSEN1 model, and how these changes affect gastrointestinal (GI) functionality, in terms of colonic contractility and motility, expression of key neurotransmitter-related proteins involved in motility, and expression of genes related to inflammation. In addition, I sought to explore whether stress (acute- restraint stress) causes alterations, at the mRNA level, of molecular machinery involved in inflammation within the colon

Date of Award	Aug 2021
Original language	English
Awarding Institution	University of Portsmouth
Supervisor	James Brown (Supervisor) & Jerome Swinny (Supervisor)