Microglia-derived neuregulin expression in psychiatric disorders.

Area of Science:

• Neuroscience
• Immunology
• Psychiatry

Background:

• Neuregulins (NRGs) play a role in brain function and psychiatric disorders.
• Microglia, immune cells in the brain, are increasingly recognized for their involvement in neurodevelopmental and psychiatric conditions.
• Previous research linked microglial activation to autism spectrum disorder (ASD).

Purpose of the Study:

• To investigate microglial neuregulin (NRG) mRNA expression in mouse models of autism spectrum disorder (ASD).
• To explore the potential of NRG expression in peripheral blood mononuclear cells (PBMCs) as a biomarker for ASD-related neuroinflammation.

Main Methods:

• Assessed microglial NRG mRNA expression in BTBR, socially-isolated, and maternal immune activation (MIA) mouse models of ASD.
• Correlated microglial NRG expression with peripheral blood mononuclear cell (PBMC) NRG expression in mice.
• Measured NRG1 splice-variant expression in PBMCs from human patients diagnosed with ASD.

Main Results:

• Microglial NRG expression was significantly elevated in BTBR and socially-isolated mice, but not in MIA mice, compared to controls.
• A positive correlation was observed between microglial and PBMC NRG expression in mice.
• NRG1 type III expression in human PBMCs positively correlated with social interaction impairments in children with ASD, as measured by the ADI-R.

Conclusions:

• Microglia are a source of neuregulins (NRGs), with increased expression in certain models of ASD.
• Peripheral NRG levels, particularly NRG1 type III in PBMCs, may serve as a potential biomarker for assessing social interaction deficits in ASD.
• Immune cell-derived NRGs are implicated in the pathobiology of psychiatric disorders, including ASD.