Maternal Immune Activation Leads to Mitochondrial Dysfunction and a Social Deficit in Offspring That Is Reversed by...

Area of Science:

• Neuroscience
• Immunology
• Mitochondrial Biology

Background:

• Maternal immune activation (MIA) is linked to neurodevelopmental disorders like schizophrenia.
• Poly(I/C) in rodent models mimics MIA, causing inflammation and behavioral deficits, including social interaction impairments.
• MIA affects mitochondrial membrane potential (ΔΨm) and protein expression in offspring brains.

Purpose of the Study:

• To investigate the persistence of mitochondrial dysfunction in MIA offspring.
• To analyze mitochondrial gene expression in the medial prefrontal cortex of MIA offspring.
• To determine if mitochondrial dysfunction contributes to behavioral deficits and if it can be therapeutically targeted.

Main Methods:

• Non-invasive in vivo monitoring of mitochondrial membrane potential (ΔΨm) using bioluminescence in juvenile and adult MIA offspring.
• Analysis of RNA sequencing data combined with MitoCarta3.0 to examine mitochondrial gene expression in the medial prefrontal cortex.
• Assessment of nicotinamide riboside's effect on ΔΨm and social interaction deficits in MIA offspring.

Main Results:

• Impaired ΔΨm maintenance was observed in MIA offspring from juvenile stages into adulthood.
• MIA significantly altered the expression of genes involved in mitochondrial energy production.
• Nicotinamide riboside treatment attenuated MIA-induced social interaction deficits and restored ΔΨm.

Conclusions:

• Mitochondrial dysfunction is a persistent consequence of MIA and contributes to behavioral deficits.
• Enhancing mitochondrial function, for example, via nicotinamide riboside, shows therapeutic potential for MIA-associated symptoms.
• Mitochondrial health represents a promising therapeutic target for schizophrenia and related disorders.