D1R-and D2R-Medium-Sized Spiny Neurons Diversity: Insights Into Striatal Vulnerability to Huntington's Disease Mutation
Open Access
- 10 February 2021
- journal article
- review article
- Published by Frontiers Media SA in Frontiers in Cellular Neuroscience
Abstract
Huntington's disease (HD) is a devastating neurodegenerative disorder caused by an aberrant expansion of the CAG tract within the exon 1 of the HD gene, HTT. HD progressively impairs motor and cognitive capabilities, leading to a total loss of autonomy and ultimate death. Currently, no cure or effective treatment is available to halt the disease. Although the HTT gene is ubiquitously expressed, the striatum appears to be the most susceptible district to the HD mutation with Medium-sized Spiny Neurons (MSNs) (D1R and D2R) representing 95% of the striatal neuronal population. Why are striatal MSNs so vulnerable to the HD mutation? Particularly, why do D1R- and D2R-MSNs display different susceptibility to HD? Here, we highlight significant differences between D1R- and D2R-MSNs subpopulations, such as morphology, electrophysiology, transcriptomic, functionality, and localization in the striatum. We discuss possible reasons for their selective degeneration in the context of HD. Our review suggests that a better understanding of cell type-specific gene expression dysregulation within the striatum might reveal new paths to therapeutic intervention or prevention to ameliorate HD patients' life expectancy.Funding Information
- H2020 Marie Skłodowska-Curie Actions
This publication has 118 references indexed in Scilit:
- Systemic Delivery of Recombinant Brain Derived Neurotrophic Factor (BDNF) in the R6/2 Mouse Model of Huntington’s DiseasePLOS ONE, 2013
- Striatal atrophy and dendritic alterations in a knock-in mouse model of Huntington's diseaseBrain Research Bulletin, 2012
- Gene expression profiling of R6/2 transgenic mice with different CAG repeat lengths reveals genes associated with disease onset and progression in Huntington's diseaseNeurobiology of Disease, 2011
- Mitochondrial fission and cristae disruption increase the response of cell models of Huntington's disease to apoptotic stimuliEMBO Molecular Medicine, 2010
- SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesisProceedings of the National Academy of Sciences of the United States of America, 2010
- Impaired mitochondrial trafficking in Huntington's diseaseBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2010
- Expression of mutant huntingtin in mouse brain astrocytes causes age-dependent neurological symptomsProceedings of the National Academy of Sciences of the United States of America, 2009
- Intergenerational and striatal CAG repeat instability in Huntington's disease knock-in mice involve different DNA repair genesNeurobiology of Disease, 2009
- Transcriptional signatures in Huntington's diseaseProgress in Neurobiology, 2007
- The corticostriatal pathway in Huntington's diseaseProgress in Neurobiology, 2007