Modulation of dopamine D₁ receptors via histamine H₃ receptors is a novel therapeutic target for Huntington's disease.

ABSTRACT: Early Huntington's disease (HD) include over-activation of dopamine D₁ receptors (D₁R), producing an imbalance in dopaminergic neurotransmission and cell death. To reduce D₁R over-activation, we present a strategy based on targeting complexes of D₁R and histamine H₃ receptors (H₃R). Using an HD mouse striatal cell model and HD mouse organotypic brain slices we found that D₁R-induced cell death signaling and neuronal degeneration, are mitigated by an H₃R antagonist. We demonstrate that the D₁R-H₃R heteromer is expressed in HD mice at early but not late stages of HD, correlating with HD progression. In accordance, we found this target expressed in human control subjects and low-grade

SUBMITTER: Moreno-Delgado D 

PROVIDER: S-EPMC7282811 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature