Intravenous MSC-Treatment Improves Impaired Brain Functions in the R6/2 Mouse Model of Huntington's Disease via Recovered Hepatic Pathological Changes
Related Experiment Video
Updated: Jun 29, 2025
Surgical Transplantation of Mouse Neural Stem Cells into the Spinal Cords of Mice Infected with Neurotropic Mouse Hepatitis Virus
Published on: July 10, 2011
Libo Yu-Taeger1,2, Ali El-Ayoubi1,2, Pengfei Qi1,2
1Department of Human Genetics, Ruhr University of Bochum, D-44801 Bochum, Germany.
Insights
Mesenchymal Stromal Cells (MSCs) treatment improved liver pathology and brain function in Huntington's disease (HD) mouse models. This suggests a potential therapeutic strategy targeting liver inflammation for HD.
Area of Science:
- Neurodegenerative Disorders
- Hepatology
- Immunology
Background:
- Huntington's disease (HD) is a congenital neurodegenerative disorder with systemic pathological effects beyond the nervous system.
- Peripheral organ dysfunction, inflammation, and gut dysbiosis are increasingly recognized in HD pathogenesis.
- Elevated pro-inflammatory cytokines correlate with disease progression in HD patients and models.
Purpose of the Study:
- To investigate hepatic pathological markers in R6/2 mouse models of HD.
- To evaluate the therapeutic potential of intravenously administered Mesenchymal Stromal Cells (MSCs) on liver pathology, brain pathology, and behavioral deficits in R6/2 mice.
Main Methods:
- Assessment of hepatic pathological markers and liver enzymes in R6/2 mice.
- Intravenous administration of MSCs to R6/2 mice.
- Evaluation of inflammatory markers, neuronal pathology, and motor activity in treated and untreated R6/2 mice.
Main Results:
- R6/2 mice exhibited altered liver enzyme expression and increased hepatic inflammatory mediators.
- MSC treatment significantly attenuated liver enzyme alterations and hepatic inflammation in R6/2 mice.
- MSC treatment ameliorated neuronal pathology and motor deficits in R6/2 mice, irrespective of MSC presence in the brain.
Conclusions:
- Hepatic pathological changes play a significant role in Huntington's disease progression.
- MSCs offer a potential therapeutic approach for HD by mitigating liver pathology and improving neurological outcomes.
- The study suggests exploring blood biomarkers for liver pathology in HD patients.
Abstract:
Huntington's disease (HD), a congenital neurodegenerative disorder, extends its pathological damages beyond the nervous system. The systematic manifestation of HD has been extensively described in numerous studies, including dysfunction in peripheral organs and peripheral inflammation. Gut dysbiosis and the gut-liver-brain axis have garnered greater emphasis in neurodegenerative research, and increased plasma levels of pro-inflammatory cytokines have been identified in HD patients and various in vivo models, correlating with disease progression. In the present study, we investigated hepatic pathological markers in the liver of R6/2 mice which convey exon 1 of the human mutant huntingtin gene. Furthermore, we evaluated the impact of intravenously administered Mesenchymal Stromal Cells (MSCs) on the liver enzymes, changes in hepatic inflammatory markers, as well as brain pathology and behavioral deficits in R6/2 mice. Our results revealed altered enzyme expression and increased levels of inflammatory mediators in the liver of R6/2 mice, which were significantly attenuated in the MSC-treated R6/2 mice. Remarkably, neuronal pathology and altered motor activities in the MSC-treated R6/2 mice were significantly ameliorated, despite the absence of MSCs in the postmortem brain. Our data highlight the importance of hepatic pathological changes in HD, providing a potential therapeutic approach. Moreover, the data open new perspectives for the search in blood biomarkers correlating with liver pathology in HD.
