Environmental Enrichment Prevents Transcriptional Disturbances Induced by Alpha-Synuclein Overexpression

Frontiers in Cellular Neuroscience
Zinah WassoufJulia M Schulze-Hentrich

Abstract

Onset and progression of neurodegenerative disorders, including synucleinopathies such as Parkinson's disease, have been associated with various environmental factors. A highly compelling association from a therapeutic point of view has been found between a physically active lifestyle and a significantly reduced risk for Parkinson's disease. Mimicking such conditions in animal models by promoting physical activity, social interactions, and novel surroundings yields in a so-called enriched environment known to enhance adult neurogenesis, increase synaptic plasticity, and decelerate neuronal loss. Yet, the genes that connect beneficial environmental cues to the genome and delay disease-related symptoms have remained largely unclear. To identify such mediator genes, we used a 2 × 2 factorial design opposing genotype and environment. Specifically, we compared wildtype to transgenic mice overexpressing human SNCA, a key gene in synucleinopathies encoding alpha-synuclein, and housed them in a standard and enriched environment from weaning to 12 months of age before profiling their hippocampal transcriptome using RNA-sequencing. Under standard environmental conditions, differentially expressed genes were overrepresented for calcium io...Continue Reading

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Citations

Dec 14, 2018·Aging·Thomas HentrichJulia M Schulze-Hentrich
Jan 11, 2020·Frontiers in Neurology·Alexander KilzheimerJulia M Schulze-Hentrich
Jan 29, 2019·Frontiers in Neuroscience·Zinah WassoufJulia M Schulze-Hentrich
May 25, 2021·Frontiers in Molecular Neuroscience·Sergio Espeso-GilStephan Ossowski
May 29, 2021·Neuropharmacology·Daniel D Cooper, Bruno G Frenguelli

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Datasets Mentioned

BETA
AC097478
GSE96961

Methods Mentioned

BETA
transgenic
PCR
biopsies
genotyping
RNA-seq

Software Mentioned

FastQC
GraphPad Prism
STAR
BestKeeper
GeneMANIA
Normfinder
Excel
Ensembl
DAVID
Integrative Genome Viewer

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