The miR-124-AMPAR pathway connects polygenic risks with behavioral changes shared between schizophrenia and bipolar disorder.
Neuron
; 111(2): 220-235.e9, 2023 01 18.
Article
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| MEDLINE
| ID: mdl-36379214
ABSTRACT
Schizophrenia (SZ) and bipolar disorder (BP) are highly heritable major psychiatric disorders that share a substantial portion of genetic risk as well as their clinical manifestations. This raises a fundamental question of whether, and how, common neurobiological pathways translate their shared polygenic risks into shared clinical manifestations. This study shows the miR-124-3p-AMPAR pathway as a key common neurobiological mediator that connects polygenic risks with behavioral changes shared between these two psychotic disorders. We discovered the upregulation of miR-124-3p in neuronal cells and the postmortem prefrontal cortex from both SZ and BP patients. Intriguingly, the upregulation is associated with the polygenic risks shared between these two disorders. Seeking mechanistic dissection, we generated a mouse model that upregulates miR-124-3p in the medial prefrontal cortex. We demonstrated that the upregulation of miR-124-3p increases GRIA2-lacking calcium-permeable AMPARs and perturbs AMPAR-mediated excitatory synaptic transmission, leading to deficits in the behavioral dimensions shared between SZ and BP.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Esquizofrenia
/
Trastorno Bipolar
/
MicroARNs
Tipo de estudio:
Etiology_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Neuron
Asunto de la revista:
NEUROLOGIA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos