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Project

Transcriptomic profiling of amyloid-induced responses in central and enteric neuronal cultures.

In recent years, growing evidence has been provided showing that disorders affecting the central nervous system (CNS) are accompanied or even preceded by neuropathological alterations in the enteric nervous system (ENS). This co-morbidity is well-described for Parkinson's disease and prion diseases, but it is still unclear whether the same holds true for disorders involving β-amyloid (Aβ) accumulation such as Alzheimer's disease (AD). Until now, it is still unclear whether enteric neurons and/or associated cells within the ENS are capable of taking up and transmitting Aβ species, in the end leading to functionally impaired enteric neurons as is the case in the CNS. As a first step in addressing these questions, we want to acquire a comprehensive view on differentially expressed genes and pathways after Aβ stimulation. Therefore, primary cultures of hippocampal and myenteric neurons will be prepared and challenged with microbial (Curli) and human-derived (Aβ42 oligomers and scrambled peptide) amyloids, as well as with known inducers of an inflammatory stress response (LPS and PolyI:C). In these samples, gene expression changes will be studied using transcriptomics, followed by validation of a subset of top hits with qPCR, Western blot and immunostainings. The results obtained in this project will fuel future research into the involvement of the microbiome-gut-brain axis in AD.
Date:1 Apr 2019 →  30 Mar 2020
Keywords:TRANSCRIPTOMICS, ALZHEIMER'S DISEASE, ENTERIC, B-AMYLOIDOSE
Disciplines:Gastro-enterology