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Peripheral nerve injury induces dystonia-like movements and dysregulation in the energy metabolism: A multi-omics descriptive study in Thap1+/− mice

ABSTRACT: DYT-THAP1 dystonia is a monogenetic form of dystonia, a movement disorder characterized by involuntary muscle contractions. The disease is caused by mutations in the THAP1 gene, although the exact mechanisms through which these mutations contribute to dystonia's pathophysiology remain elusive. The incomplete penetrance of DYT-tHAP1 dystonia, estimated between 40-60%, indicated that an environmental trigger might be necessary for the disease to manifest in genetically predisposed individuals. To explore the gene-environment interaction in dystonia development, we performed a sciatic nerve crush injury in a genetically predisposed DYTHAP1 heterozygous knockout mouse mode (Thap1+/-). Using a multi-omic approach, we investigated the underlying pathophysiological pathways. Phenotypic analysis with an unbiased deep learning algorithm showed that nerve-injured Thap1+/- mice exhibited more dystonia-like movements over the 12-week experiment than naive Thap1+/- mice. Multi-omic analysis of the cerebellum, striatum, and cortex in nerve-injured Thap1+/- mice revealed altered energy metabolism compared to naive Thap1+/- and nerve-injured wildtype mice. These findings suggest that abnormal energy metabolism in the cerebellum, striatum, and cortex may contribute to the dystonic features observed in nerve-injured Thap1+/- mice.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Colette Reinhold

LAB HEAD: Chi Wang

PROVIDER: PXD055364 | Pride | 2025-01-03

REPOSITORIES: Pride

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	2023-03-16_Fusion_36527.raw	Raw
	2023-03-16_Fusion_36528.raw	Raw
	2023-03-16_Fusion_36529.raw	Raw
	2023-03-16_Fusion_36530.raw	Raw
	2023-03-16_Fusion_36531.raw	Raw

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