Genetic liability underlying reward-related comorbidity in psychiatric disorders involves the coincident functions of autism–linked ADGRL1 and hevin DOI
Kerlys G. Correoso‐Braña, Augusto Anésio, Sylvie Dumas

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 5, 2024

ABSTRACT Comorbidity between psychiatric traits is thought to involve overlapping pleiotropic effects from sets of genes. Notably, substance abuse a shared comorbid condition among various neurodevelopmental disorders with externalizing symptoms such as autism spectrum disorder and attention-deficit hyperactivity disorder, thus hinting at the nucleus accumbens (NAc) site for predisposition underlying convergence genetic influences in reward-related comorbidity. Here, we identify autism-related gene encoding adhesion G protein-coupled receptor (aGPCR) Latrophilin-1/ADGRL1 an essential transducer reward mechanisms NAc. We found that ADGRL1 mRNA ubiquitously expressed throughout major NAc neuronal populations mice. A mouse model pan-neuronal Adgrl1 deficiency displayed cocaine-seeking impairments adult individuals denoting its role drug-induced reinforcement reward. Connecting molecular pathways cocaine-induced learning, uncover constitutes functional cocaine effector molecule hevin/SPARCL1. Indeed, hevin interacts membrane-expressed induces internalization while stabilizing uncleaved fraction. Moreover, alters formation intercellular contacts mediated by Neurexin-1. Importantly, constitutive coupling protein selectively modulated stimulation bias toward Gi3, Gs, G13 proteins. These findings unveil dual risk factors both define etiology

Language: Английский

Genetic liability underlying reward-related comorbidity in psychiatric disorders involves the coincident functions of autism–linked ADGRL1 and hevin DOI
Kerlys G. Correoso‐Braña, Augusto Anésio, Sylvie Dumas

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 5, 2024

ABSTRACT Comorbidity between psychiatric traits is thought to involve overlapping pleiotropic effects from sets of genes. Notably, substance abuse a shared comorbid condition among various neurodevelopmental disorders with externalizing symptoms such as autism spectrum disorder and attention-deficit hyperactivity disorder, thus hinting at the nucleus accumbens (NAc) site for predisposition underlying convergence genetic influences in reward-related comorbidity. Here, we identify autism-related gene encoding adhesion G protein-coupled receptor (aGPCR) Latrophilin-1/ADGRL1 an essential transducer reward mechanisms NAc. We found that ADGRL1 mRNA ubiquitously expressed throughout major NAc neuronal populations mice. A mouse model pan-neuronal Adgrl1 deficiency displayed cocaine-seeking impairments adult individuals denoting its role drug-induced reinforcement reward. Connecting molecular pathways cocaine-induced learning, uncover constitutes functional cocaine effector molecule hevin/SPARCL1. Indeed, hevin interacts membrane-expressed induces internalization while stabilizing uncleaved fraction. Moreover, alters formation intercellular contacts mediated by Neurexin-1. Importantly, constitutive coupling protein selectively modulated stimulation bias toward Gi3, Gs, G13 proteins. These findings unveil dual risk factors both define etiology

Language: Английский

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