2026-04-17T05:50:52Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1780572025-12-04T21:12:42Zcom_2072_1057col_2072_478781col_2072_478917

00925njm 22002777a 4500 dc Moreno-Delgado, David author Puigdellívol, Mar author Moreno Guillén, Estefanía author Rodríguez-Ruiz, Mar author Botta, Joaquín author Gasperini, Paola author Chiarlone, Anna author Howell, Lesley A. author Scarselli, Marco author Casadó, Vicent author Cortés Tejedor, Antonio author Ferré, Sergi author Guzmán, Manuel author Lluís i Biset, Carme author Alberch i Vié, Jordi, 1959- author Canela Campos, Enric I. (Enric Isidre), 1949- author Ginés, Silvia author McCormick, Peter J. author 2021-06-07T15:17:15Z 2021-06-07T15:17:15Z 2020-06-09 2021-06-07T15:17:15Z 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 HD patients. Finally, treatment of HD mice with an H3R antagonist prevented cognitive and motor learning deficits and the loss of heteromer expression. Taken together, our results indicate that D1R - H3R heteromers play a pivotal role in dopamine signaling and represent novel targets for treating HD. Corea de Huntington Histamina Dopamina Huntington's chorea Histamine Dopamine Modulation of Dopamine D1 receptors via histamine H3 receptors is a novel therapeutic target for Huntington's disease