Decreased number and increased activation state of astrocytes in gray and white matter of the prefrontal cortex in autism.

Scientists studied brain cells called astrocytes in people with autism after death. They found fewer of these important support cells in the front part of the brain, and the remaining cells showed signs of being more 'activated' or inflamed. This could help explain some brain differences in autism, as these cells normally help brain connections work properly.

This post-mortem brain study examined astrocytes (supportive brain cells) in the prefrontal cortex of 15 individuals with autism compared to 15 matched controls. Researchers found significantly fewer astrocytes in both gray and white matter across three prefrontal brain regions (BA9, BA46, BA47) using two different cellular markers (GFAP and S100β). Additionally, the remaining astrocytes showed increased activation states, suggesting heightened inflammatory activity. The reduced astrocyte numbers could impair synaptic function and brain connectivity, while increased activation may indicate chronic mild inflammation in the autism brain.

These findings suggest astrocyte dysfunction may contribute to autism pathophysiology.

Findings suggest astrocyte dysfunction may be a target for future autism interventions. However, these are post-mortem findings that require validation in living brain studies. The inflammatory component suggests anti-inflammatory approaches might be investigated, though clinical translation remains uncertain.

Small sample size (15 per group), post-mortem tissue analysis only, limited to prefrontal cortex regions, cross-sectional design cannot establish causality, potential confounding factors in post-mortem studies not addressed.

The cerebral cortex presents with alterations in the number of specific cell types in autism spectrum disorder (ASD). Astrocytes have many functions in the brain including a role in higher cognitive functions and in inflammatory brain processes. Therefore, an alteration in number, function, and/or activation state of astrocytes, could be present in ASD. We quantified astrocyte number in the gray and white matter of the prefrontal cortex-BA9, BA46, and BA47-in 15 ASD and 15 age- and sex-matched control cases.

We labeled astrocytes with antibodies against the protein GFAP and S100β, markers of astrocytes. We found a significant decrease in the number of astrocytes in the gray and white matter of all prefrontal areas of interest with both markers. We also found an increased state of activation of GFAP+ astrocytes in all areas. A reduced number of astrocytes in the cerebral cortex in ASD could lead to impaired synaptic function and disrupted connectivity.

An increased astrocyte activation may indicate a chronic mild inflammatory state of the cerebral cortex in ASD. Overall, we found that astrocytes are disrupted in ASD.