Prenatal immune activation in mice induces long-term alterations in brain mitochondrial function

Area of Science:

• Neuroscience
• Developmental Biology
• Mitochondrial Biology

Background:

• Prenatal infections are linked to neurodevelopmental disorders.
• Mitochondrial dysfunction is a proposed mechanism for these disorders.

Purpose of the Study:

• To investigate the effects of maternal immune activation (MIA) on offspring brain mitochondrial function.
• To examine sex-specific alterations in mitochondrial respiration, mass, and gene expression.

Main Methods:

• Used a poly(I:C) mouse model to simulate viral-like MIA at gestational day 12.
• Assessed behavioral deficits, mitochondrial respiration (NADH- and succinate-linked), mitochondrial mass, and gene expression in adult offspring's prefrontal cortex and amygdala.

Main Results:

• MIA offspring showed reduced social interaction and altered mitochondrial respiration and mass in the prefrontal cortex and amygdala.
• Males exhibited reduced mitochondrial coupling efficiency and uncoupling protein expression post-MIA.
• Females showed higher baseline antioxidant enzyme expression, suggesting sex-specific responses.

Conclusions:

• Maternal immune activation induces significant alterations in neuronal mitochondrial function and mass in adult offspring.
• These MIA-induced mitochondrial changes in the brain may contribute to neurodevelopmental and behavioral deficits.
• Sex-specific differences in mitochondrial responses to MIA were observed.