Synaptotagmin-11 deficiency mediates schizophrenia-like behaviors in mice via dopamine over-transmission.

ABSTRACT: Schizophrenia is a severe neuropsychiatric disease, but the initiation mechanisms are unclear. Although antipsychotics are effective against positive symptoms, therapeutic interventions for negative symptoms are limited due to the lack of pathophysiological mechanisms. Here we identify synaptotagmin-11 (Syt11) as a potential genetic risk factor and dopamine over-transmission as a mechanism in the development of schizophrenia. Syt11 expression is reduced in individuals with schizophrenia but restored following the treatment with antipsychotics. Syt11 deficiency in dopamine neurons in early adolescence, but not in adults, leads to persistent social deficits and other schizophrenia-like behaviors by mediating dopamine over-transmission in mice. Accordingly, dopamine neuron over-excitation bef

SUBMITTER: Chen Y 

PROVIDER: S-EPMC11618495 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature