Changes in protein markers of the mitochondrial respiratory chain and quality control in a mouse model of psychosis.

Alterations in mitochondrial function and mitochondrial quality control (MQC) in the CNS have been consistently associated with neurological disorders, but are less investigated in psychiatric disorders. We measured levels of mitochondrial proteins involved in oxidative phosphorylation and MQC in a neurodevelopmental mouse model that recapitulates some of the features of schizophrenia. We used adult male and female mice prenatally exposed to the toxin, methylazoxymethanol (MAM, injected i.p. to pregnant dams, daily from gestational day 15 to 17, at the dose of 10 mg/kg). This treatment caused abnormalities in locomotor activity, social interaction, novel object recognition, and prepulse inhibition of acoustic startle in the adult offspring. MAM-treated mice showed sex-dimorphic changes in proteins of complex I and IV of the mitochondrial respiratory chain, as well as changes in proteins involved in mitochondrial fusion and fission (mitofusin-1 and -2 and dynamin-related protein-1, respectively), mitophagy (PTEN-induced kinase-1, Rab5 and Rab7a), and mitochondrial biogenesis (peroxisome proliferator-activated receptor γ-coactivator-1α, nuclear respiratory factors 1 and - 2, and mitochondrial transcription factor-B2). To our knowledge, this is the first extensive study of mitochondrial proteins in preclinical models of schizophrenia, and our data pave the way to a focused investigation of mitochondrial morphology and function in MAM-treated mice of both sexes.