ArticleFrontiers in molecular neuroscience2022
Metabotropic Glutamate Receptor 5 Antagonism Reduces Pathology and Differentially Improves Symptoms in Male and Female Heterozygous zQ175 Huntington's Mice.
Article in Frontiers in molecular neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 18 citations in OpenAlex.
- Altered Excitation-Inhibition Balance and mGluRInternational journal of molecular sciences · 2026Article
- Neuroglial Function and Hormonal Modulation in Neurodegenerative Diseases: The Influence of Sex Hormones.Cellular and molecular neurobiology · 2026Review
- Engram cell vulnerability in neurodegeneration: from mechanistic insights to therapeutic horizons.Frontiers in aging neuroscience · 2026Review
- Pharmacology, Signaling and Therapeutic Potential of Metabotropic Glutamate Receptor 5 Negative Allosteric Modulators.ACS pharmacology & translational science · 2024Review
- GET73 modulates lipopolysaccharide- and ethanol-induced increase in cytokine/chemokine levels in primary cultures of microglia of rat cerebral cortex.Pharmacological reports : PR · 2024Article
- Sex differences in Huntington's disease from a neuroinflammation perspective.Frontiers in neurology · 2024Article
- Amyloid-βiScience · 2023Article
- Small Molecule Pytren-4QMn Metal Complex Slows down Huntington's Disease Progression in Male zQ175 Transgenic Mice.International journal of molecular sciences · 2023Article
- Comparison of Huntington's disease phenotype progression in male and female heterozygous FDNQ175 mice.Molecular brain · 2023Article
- VGLUT3 Deletion Rescues Motor Deficits and Neuronal Loss in the zQ175 Mouse Model of Huntington's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Sex differences and hormonal regulation of metabotropic glutamate receptor synaptic plasticity.International review of neurobiology · 2023Review
- mGluR5 ablation leads to age-related synaptic plasticity impairments and does not improve Huntington's disease phenotype.Scientific reports · 2022Article
- Targeting the Type 5 Metabotropic Glutamate Receptor: A Potential Therapeutic Strategy for Neurodegenerative Diseases?Frontiers in pharmacology · 2022Review
- Sex-dependence of synaptic depression induced by activation of metabotropic glutamate receptors in rat hippocampus.Brain and neuroscience advancesArticle
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Huntington's disease (HD) is an inherited autosomal dominant neurodegenerative disorder that leads to progressive motor and cognitive impairment. There are currently no available disease modifying treatments for HD patients. We have previously shown that pharmacological blockade of metabotropic glutamate receptor 5 (mGluR5) signaling rescues motor deficits, improves cognitive impairments and mitigates HD neuropathology in male zQ175 HD mice. Mounting evidence indicates that sex may influence HD progression and we have recently reported a sex-specific pathological mGluR5 signaling in Alzheimer's disease (AD) mice. Here, we compared the outcomes of treatment with the mGluR5 negative allosteric modulator CTEP (2-chloro-4-[2-[2,5-dimethyl-1-[4-(trifluoromethoxy)phenyl]imidazol-4-yl]ethynyl]pyridine) in both male and female symptomatic zQ175 mice. We found that female zQ175 mice required a longer treatment duration with CTEP than male mice to show improvement in their rotarod performance. Unlike males, chronic CTEP treatment did not improve the grip strength nor reverse the cognitive decline of female zQ175 mice. However, CTEP reduced the number of huntingtin aggregates, improved neuronal survival and decreased microglia activation in the striatum of both male and female zQ175 mice. Together, our results indicate that mGluR5 antagonism can reduce HD neuropathology in both male and female zQ175 HD mice, but sex has a clear impact on the efficacy of the treatment and must be taken into consideration for future HD drug development.
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