Two distinct microglia populations linked to autism-like and depression-like behaviors in mice

The anterior insular cortex (aIC) is an important brain region known to contribute to the regulation of emotions, the integration of bodily sensations, decision-making and some other functions. Past studies have linked this brain region to some neuropsychiatric disorders characterized by unusual patterns of thinking and behavior, including autism spectrum disorder (ASD) and depression.

However, the precise cellular and neurobiological processes via which the aIC might contribute to ASD and depression have not yet been clearly elucidated. Some neuroscientists have been exploring the possibility that microglia, immune cells that play a role in eliminating damaged cells and pathogens, could play a role in some of the behaviors linked with these two neuropsychiatric disorders.

Researchers at Tsinghua University recently carried out a study involving mice, aimed at investigating the possibility that microglia in the aIC play a part in some of the symptoms of ASD and depression. Their paper, published in Molecular Psychiatry, identifies two distinct subtypes of microglia that appear to contribute to autism-like and depression-like behavior in mice.

“Using the Cntnap2-deficient autism spectrum disorder (ASD) mouse model and the chronic social defect stress (CSDS)-induced depression mouse model, we show that two subpopulations of microglia in the mouse aIC played differential roles in ASD-like and depression-like behavioral phenotypes differentially,” Qiao-Ming Zhang, Yan-Fen Chen and their colleagues wrote in their paper.

The researchers carried out their experiments on two types of mice that exhibited behaviors resembling those commonly observed in people diagnosed with ASD and depression, respectively. The first group of mice (Cntnap2-deficient mice) was genetically modified and lacked the Cntnap2 gene. Mutations of this gene have been linked to ASD in humans.

The second set of mice (CSDS-induced mice) had been previously exposed to a larger and aggressive mouse over the course of several days. This can cause chronic stress, prompting mice to develop depression-like symptoms.

“The Cx3cr1⁺ microglia had morphological deficits in the Cntnap2-deficient mice and were involved in social deficits and restricted repetitive behaviors, while the Tmem119⁺ microglia had morphological deficits in the CSDS-induced mice and contributed to impairments in sucrose preference and forced swim performance,” wrote Zhang, Chen and their colleagues.

“Further, we showed that the two subsets of microglia had differential features in morphology, transcriptional profiles, electrophysiological properties, and impacts on synaptic functions.”

Essentially, the researchers linked abnormalities in two microglia sub-populations, namely Cx3cr1⁺ microglia and Tmem119⁺ microglia, to ASD-like and depression-like behaviors, respectively. The Cx3cr1⁺ microglia in the brains of mice exhibiting ASD-like behavior were found to look abnormal, while CSDS-induced mice exhibited abnormalities in Tmem119⁺ microglia.

“Using proteomic and metabonomic analyses, we identified two secretory factors, Fbl and Hp1bp3, that were crucial for the dysfunctions of the Cx3cr1⁺ and Tmem119⁺ microglia, respectively,” wrote the authors. “Finally, we verified that Fbl and Hp1bp3 played essential roles in the behavioral deficits of the Cntnap2-deficient and the CSDS-induced mice, respectively.”

Overall, the findings suggest that different types of microglia play a role in the behaviors characterizing ASD and depression. In the future, other researchers could explore the possibility that specific microglia populations are associated with other neuropsychiatric disorders. If they are found to apply to humans, the results of this study could potentially also inspire the development of new experimental treatments for ASD or depression that target specific microglia subtypes.

© 2025 Science X Network

The anterior insular cortex (aIC) is an important brain region known to contribute to the regulation of emotions, the integration of bodily sensations, decision-making and some other functions. Past studies have linked this brain region to some neuropsychiatric disorders characterized by unusual patterns of thinking and behavior, including autism spectrum disorder (ASD) and depression.

However, the precise cellular and neurobiological processes via which the aIC might contribute to ASD and depression have not yet been clearly elucidated. Some neuroscientists have been exploring the possibility that microglia, immune cells that play a role in eliminating damaged cells and pathogens, could play a role in some of the behaviors linked with these two neuropsychiatric disorders.

Researchers at Tsinghua University recently carried out a study involving mice, aimed at investigating the possibility that microglia in the aIC play a part in some of the symptoms of ASD and depression. Their paper, published in Molecular Psychiatry, identifies two distinct subtypes of microglia that appear to contribute to autism-like and depression-like behavior in mice.

“Using the Cntnap2-deficient autism spectrum disorder (ASD) mouse model and the chronic social defect stress (CSDS)-induced depression mouse model, we show that two subpopulations of microglia in the mouse aIC played differential roles in ASD-like and depression-like behavioral phenotypes differentially,” Qiao-Ming Zhang, Yan-Fen Chen and their colleagues wrote in their paper.

The researchers carried out their experiments on two types of mice that exhibited behaviors resembling those commonly observed in people diagnosed with ASD and depression, respectively. The first group of mice (Cntnap2-deficient mice) was genetically modified and lacked the Cntnap2 gene. Mutations of this gene have been linked to ASD in humans.

The second set of mice (CSDS-induced mice) had been previously exposed to a larger and aggressive mouse over the course of several days. This can cause chronic stress, prompting mice to develop depression-like symptoms.

“The Cx3cr1⁺ microglia had morphological deficits in the Cntnap2-deficient mice and were involved in social deficits and restricted repetitive behaviors, while the Tmem119⁺ microglia had morphological deficits in the CSDS-induced mice and contributed to impairments in sucrose preference and forced swim performance,” wrote Zhang, Chen and their colleagues.

“Further, we showed that the two subsets of microglia had differential features in morphology, transcriptional profiles, electrophysiological properties, and impacts on synaptic functions.”

Essentially, the researchers linked abnormalities in two microglia sub-populations, namely Cx3cr1⁺ microglia and Tmem119⁺ microglia, to ASD-like and depression-like behaviors, respectively. The Cx3cr1⁺ microglia in the brains of mice exhibiting ASD-like behavior were found to look abnormal, while CSDS-induced mice exhibited abnormalities in Tmem119⁺ microglia.

“Using proteomic and metabonomic analyses, we identified two secretory factors, Fbl and Hp1bp3, that were crucial for the dysfunctions of the Cx3cr1⁺ and Tmem119⁺ microglia, respectively,” wrote the authors. “Finally, we verified that Fbl and Hp1bp3 played essential roles in the behavioral deficits of the Cntnap2-deficient and the CSDS-induced mice, respectively.”

Overall, the findings suggest that different types of microglia play a role in the behaviors characterizing ASD and depression. In the future, other researchers could explore the possibility that specific microglia populations are associated with other neuropsychiatric disorders. If they are found to apply to humans, the results of this study could potentially also inspire the development of new experimental treatments for ASD or depression that target specific microglia subtypes.

© 2025 Science X Network