D1R- and D2R-Medium-Sized Spiny Neurons Diversity: Insights Into Striatal Vulnerability to Huntington's Disease Mutation

Huntington's disease (HD) is a devastating neurodegenerative disorder caused by an aberrant expansion of the CAG tract within the exon 1 of the gene, . HD progressively impairs motor and cognitive capabilities, leading to a total loss of autonomy and ultimate death. Currently, no cure or effect...

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Bibliographic Details
Published in:Frontiers in cellular neuroscience 2021-02, Vol.15, p.628010-628010
Main Authors: Bergonzoni, Guendalina, Döring, Jessica, Biagioli, Marta
Format: Article
Language:English
Subjects:
Atrophy
Autonomy
Brain
Brain-derived neurotrophic factor
Cognitive ability
D1R
Dopamine
Electrophysiology
Gene expression
Huntingtin
Huntington's disease
Huntingtons disease
Kinases
Life span
Localization
medium-sized spiny neurons
Metabolism
Mutation
Neostriatum
Neurodegeneration
Neurodegenerative diseases
Neuroscience
Physiology
Polyglutamine
selective vulnerability
Spiny neurons
striatum
Trinucleotide repeats
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Summary:Huntington's disease (HD) is a devastating neurodegenerative disorder caused by an aberrant expansion of the CAG tract within the exon 1 of the gene, . 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 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.
ISSN:1662-5102
1662-5102
DOI:10.3389/fncel.2021.628010