Cells
July 27, 2021
Dasiel O. Borroto‐escuela, Patrizia Ambrogini, Manuel Narváez et al.
29 citations
Heteroreceptor complexes represent a new biological principle for signal integration in the brain, with bidirectional allosteric receptor–receptor interactions offering novel targets for treating CNS diseases, including mental disorders. The existence of D2R-5-HT2AR heterocomplexes can explain the anti-schizophrenic effects of atypical antipsychotics through blocking the allosteric enhancement of D2R signaling by 5-HT2AR activation. This principle also helps understand mechanisms of 5-HT hallucinogens like psilocybin and the prosocial, anti-stress actions of MDMA. GalR1-GalR2 heterodimers and putative GalR1-GalR2-5-HT1 complexes are targets for galanin fragment Gal(1–15) in modulating emotional networks. Antidepressant drugs, including TCAs, SSRIs, and ketamine, can directly bind to the TrkB receptor, providing a novel mechanism for their actions. Astrocytes and their allosteric receptor–receptor interactions in modulating forebrain glutamate synapses are relevant to major depressive disorder research.
Cells
April 12, 2024
Carlos Arrabal-Gómez, Rasiel Beltran-Casanueva, Aracelis Hernández-García et al.
7 citations
A single dose combining a neuropeptide Y Y1 receptor agonist with ketamine enhanced memory consolidation and increased production of new neurons (neuroblasts) in the dorsal hippocampus of male rats, without affecting quiescent neural progenitors or astrocytes. The effects were linked to brain-derived neurotrophic factor and suggested the formation of NPY1R-TrkB heteroreceptor complexes, though this interaction requires further confirmation. The findings point to a potential therapeutic approach for neurodegenerative diseases.
Expert opinion on therapeutic targets
April 1, 2024
Carlos Arrabal-Gómez, Pedro Serrano-Castro, Jose Andrés Sánchez-Pérez et al.
7 citations
A combination of an NPY1R agonist and Ketamine, given together to rodents, produced stronger antidepressant-like effects than either drug alone. The animals showed less immobility in a forced swimming test, a standard measure of antidepressant activity. This behavioral change was linked to increased formation of NPY1R/TrkB receptor complexes and higher levels of brain-derived neurotrophic factor (BDNF) in the ventral dentate gyrus of the hippocampus, along with increased neurogenesis. The results suggest that co-activating NPY1R and TrkB pathways may represent a novel therapeutic strategy for major depressive disorder that warrants further clinical investigation.