- The study of neurodegeneration in in vitro cell culture models using quantitative fluorescence microscopy and high-content screening - Studying the role of the microbiome-gut-brain axis in neurodegeneration with in vitro, ex vivo and in vivo preclinical models
Mapping amyloid-induced neurodegeneration in the gut using MALDI imaging.
AbstractAlzheimer's disease (AD) is the most prevailing form of dementia worldwide. In light of the aging population and absence of a cure, alternative research paths are being explored to tackle the disease at an early stage. Recent evidence suggests that the gut could play an important role in AD pathogenesis as it is continuously exposed to amyloids and is vulnerable to inflammatory stimuli that compromise its integrity. Current experimental methods for querying pathological signatures in gut tissue are either destructive or not sufficiently specific. Hence, we propose to use Matrix-Assisted Laser Desorption Ionization – Mass Spectrometry Imaging (MALDI-MSI) to quantify amyloid pathology and the associated proteomic changes in a comprehensive and spatially resolved manner. We will apply this technique to a mouse model that displays an accelerated aging phenotype, and develops the typical hallmarks of AD. To validate amyloid enrichment therein, we will make use of fluorescent markers, and as internal control, we will compare gut with brain tissue. In the spirit of the recently established valorization platform IMARK, this new collaborative initiative between the laboratory of Cell Biology and Histology and the Centre for Proteomics should facilitate the discovery of novel early biomarkers for AD in an organ that is much more accessible than the brain.
- Promotor: Verstraelen Peter
Transcriptomic profiling of amyloid-induced responses in central and enteric neuronal cultures.
AbstractIn 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.
- Promotor: Verstraelen Peter