A038 Systems modeling for gene-targeted homeostatic reprogramming of vulnerable striatal GABA-ergic neurons in Huntington’s disease
Year: 2024
Type: conference-paper
Abstract: Background GABA-ergic neuron vulnerability in neurodegenerative diseases such as repeat expansion diseases (REDs) is poorly understood on a systems level. Method Using innovative systems modeling methods (network analysis Rando-SDS; shape deformation analysis Geomic v2) to leverage omics data from Huntington’s disease (HD) model knock-in (Hdh) mice and from wild-type aging mice, complemented by biological studies in mice and mutant Huntingtin flies, we study genes that in disease-vulnerable GABA-ergic neurons, the medium-spiny-neurons (MSNs) of the striatum, are dysregulated in Hdh mice and show changes in ribosome-associated mRNA levels or show ribosome-associated 3’ UTR accumulation in the aging mouse brain. Results We identified several categories of dysregulation that show CAG repeat dependence and that differ in Hdh mice at moderate compared to advanced behavioral symptom timepoints. Conclusion We will discuss how our studies may provide a molecular framework for investigating the use of homeostatic reprogramming as an early-stage strategy to render vulnerable GABA-ergic neurons and the neuronal circuits in which they function more resilient in REDs such as HD.
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4402374290