The anterior insular cortex (aIC) is a critical brain area involved in emotion regulation, bodily sensation integration, decision-making, and other functions. Previous research has connected this region to neuropsychiatric disorders like autism spectrum disorder (ASD) and depression.
However, the specific cellular and neurobiological mechanisms by which the aIC might contribute to ASD and depression are still unclear. Some neuroscientists have been examining whether microglia – immune cells that help clear damaged cells and pathogens – play a role in behaviors associated with these conditions.
A recent study from Tsinghua University used mice to explore the hypothesis that microglia in the aIC affect symptoms of ASD and depression. Their findings, published in Molecular Psychiatry, identified two distinct microglia subtypes linked to autism-like and depression-like behaviors in mice.
Molecular Psychiatry"Using Cntnap2-deficient mice as an ASD model and CSDS-induced mice for depression, we found that two subpopulations of microglia in the aIC differentially impacted ASD-like and depression-like behaviors," stated Qiao-Ming Zhang, Yan-Fen Chen, and colleagues in their paper.
The researchers worked with two mouse groups exhibiting behaviors similar to those seen in humans with ASD and depression. The first group (Cntnap2-deficient mice) lacked the Cntnap2 gene due to genetic modification, a gene associated with ASD. The second set (CSDS-induced mice) had been subjected to prolonged exposure to a larger aggressive mouse, inducing depression-like symptoms.
"The Cx3cr1+ microglia exhibited deficits in morphology for the Cntnap2-deficient mice and were involved in social deficits and repetitive behaviors, while Tmem119+ microglia had morphological defects in CSDS-induced mice and contributed to impairments in sucrose preference and forced swim performance," detailed Zhang, Chen, and their colleagues.
"We also revealed that these microglia subsets differed in morphology, transcriptional profiles, electrophysiological properties, and synaptic function impacts."
In essence, the researchers linked abnormalities in two subpopulations of microglia – Cx3cr1+ and Tmem119+ – to ASD-like and depression-like behaviors. They found morphological irregularities in Cx3cr1+ microglia in ASD mice and in Tmem119+ microglia in depression mice.
"Proteomic and metabonomic analyses identified two key secretory factors, Fbl and Hp1bp3, essential for the dysfunctions of Cx3cr1+ and Tmem119+ microglia respectively," the authors wrote. "Finally, we confirmed that both Fbl and Hp1bp3 played crucial roles in behavioral deficits seen in Cntnap2-deficient and CSDS-induced mice."
These findings indicate that different microglia types may help drive behaviors characteristic of ASD and depression. Further research could explore whether specific microglia populations are linked to other neuropsychiatric disorders, potentially paving the way for new therapeutic approaches targeting these subtypes.