Impact of Early-Life Stress on Astrocytes and Behavior: Sex-Specific Brain Changes
New study reveals how early-life stress causes lasting changes in astrocytes, influencing behavior differently in males and females, with implications for depression treatment.
Recent research led by scientists at the University of Montreal has shed light on how early-life stress can cause lasting changes in brain cells called astrocytes, which in turn influence behavioral patterns in mice. The study focused on the lateral hypothalamus, a brain region critical for sleep-wake regulation, which is impacted by astrocyte activity.
The team, headed by Ciaran Murphy-Royal from the CRCHUM, discovered that early-life stress—simulated by maternal separation during a critical developmental period—altered astrocyte morphology. In female mice, astrocytes exhibited reduced size and fewer branches, indicating dysfunction. These morphological changes correlated with behavioral differences: females showed decreased activity at night, whereas males displayed hyperactivity during the day. Such sex-specific responses mirror observations in humans with depression who experienced similar early stress.
The study also explored molecular mechanisms underlying these changes. Researchers found that stress increased corticosterone levels, affecting astrocyte-neuron interactions. When they genetically removed glucocorticoid receptors—the targets of corticosterone—in astrocytes, the mice's neuronal activity and behaviors returned to baseline, despite the astrocytes not fully regaining their original size. This indicates stress impacts astrocytes before neurons and suggests a pivotal role for astrocytes in mediating stress effects.
These findings provide new insights into how early-life adversity can lead to persistent brain and behavior alterations through astrocyte dysfunction. Targeting astrocytes may open new avenues for preventing or treating depression rooted in childhood stress. As this research progresses, understanding sex differences and molecular pathways involved could lead to more effective, tailored therapies.
For more information, see the full study published in Nature Communications: [DOI: 10.1038/s41467-025-61643-y].
source: https://medicalxpress.com/news/2025-09-early-life-stress-astrocytes-affect.html
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