Researchers found that brain tissue samples from patients with epilepsy contained immature astroglia cells that tracked with lower fluid intelligence scores, according to a study published in Frontiers in Cellular Neuroscience. The research links these star-shaped support cells to human cognitive decline.
Abnormal astroglia numbers correlate with poorer cognitive performance
Scientists in the USC Stem Cell lab of Michael Bonaguidi analyzed surgically removed hippocampal tissue from patients with medically resistant mesial temporal lobe epilepsy. These pathological immature astroglia were identified by a star-like morphology and the expression of doublecortin, or Dcx. Their numbers increased with age in the dentate gyrus molecular layer.
Patients completed cognitive testing before their surgeries. Results showed that higher numbers of these abnormal immature astroglia correlated with poorer performance on Raven’s Progressive Matrices, a nonverbal measure of abstract reasoning and fluid intelligence. Among 15 measured cognitive domains, fluid intelligence, reasoning, visuospatial reconstruction, and visuospatial memory exhibited the clearest age-associated drops.
Statistical Weight of Age and Astroglia
Statistical models revealed that age contributed the largest share of residual variance in fluid intelligence, accounting for 12.6% to 25.4%. Astroglial measures contributed between 8.3% and 15.6%, while disease duration accounted for 3.3% to 4.1%. When researchers controlled for age alongside astroglial counts, the negative relationship between age and intelligence remained significant, whereas the predictive value of the astroglial counts alone lost statistical significance.
This observational study does not establish that immature astroglia directly cause intelligence to decline. Instead, it identifies a cellular feature for investigating cognitive deterioration.
Therapeutic Targets for Cognitive Decline
Aswathy Ammothumkandy, assistant professor of research in the Department of Stem Cell Biology and Regenerative Medicine at the Keck School of Medicine of USC and first author of the study, noted that older patients tended to harbor more abnormal immature astroglia. Future drug development could target these cells to slow or potentially reverse age-related cognitive drops.
Investigators are now searching for molecular differences in immature astroglia by comparing epilepsy tissue samples with control samples. Beyond small-molecule drugs, researchers suggest future work might explore neuromodulation techniques utilizing electrical or magnetic stimulation to restore healthier astroglial function.
Researchers examine surgically removed hippocampal tissue
What specific brain region did researchers examine?
Scientists analyzed tissue surgically removed from the hippocampus, obtained from patients with mesial temporal lobe epilepsy.
How were the immature astroglia identified under a microscope?
Researchers identified the cells using a star-like morphology combined with the expression of doublecortin, or Dcx, which served as a practical cellular index.
What test measured fluid intelligence in the study participants?
Participants completed Raven’s Progressive Matrices, which functions as a nonverbal measure of abstract reasoning and fluid intelligence.
Who funded and published the research?
The study received support in part from the National Institutes of Health and appeared in the peer-reviewed journal Frontiers in Cellular Neuroscience in 2026.
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