Adolescent Binge Drinking Causes Lasting Astrocyte-Synaptic Disruption, Pointing to New Treatment Targets
核心洞察
New research from Marshall University shows adolescent binge alcohol exposure disrupts astrocyte-synapse communication in the hippocampus, with changes persisting into adulthood even after prolonged abstinence.
The study, published in Molecular Psychiatry, used a preclinical rat model and advanced techniques including fiber photometry, chemogenetics, and STED microscopy to examine the dorsal hippocampus.
Stimulating calcium signaling within astrocytes (搜索) partially reduced heightened fear responses and increased gliotransmitter availability, rescuing critical cell-to-cell communication.
New research from the Marshall University Joan C. Edwards School of Medicine (搜索) provides insight into how binge alcohol exposure during adolescence may cause lasting changes in brain function that persist into adulthood, potentially identifying a new target for future treatment approaches. The study, published August 15 in Molecular Psychiatry, found that intermittent ethanol exposure during adolescence disrupted communication between astrocytes (搜索)—supportive brain cells increasingly recognized for their role in neural signaling—and synapses in the hippocampus, a region of the brain important for learning and memory.
Researchers found that these structural and functional changes persisted into adulthood, even after a prolonged period without alcohol. Remarkably, improving astrocyte function could partially recover these effects. The findings help explain potential biological mechanisms underlying the long-term cognitive and mental health outcomes associated with adolescent binge alcohol exposure, as well as reveal new pharmacological targets for repair.
"Human studies have shown that adolescent binge drinking can drive long-term impairment in cognition and worsen mental health outcomes that are risk factors for alcohol and substance use disorders," said Mary-Louise Risher, PhD, associate professor at the Joan C. Edwards School of Medicine. "Moreover, early onset binge drinking has been shown to directly increase the likelihood of developing alcohol use disorder (搜索). Understanding why binge drinking specifically during adolescence worsens mental health outcomes and reduces overall quality of life is the goal of this research. From these studies, we aim to increase public awareness and develop new therapeutic approaches to alleviate the long-term consequences of adolescent binge drinking."
Preclinical Model and Methodology
Using a preclinical rat model of adolescent intermittent ethanol (AIE), researchers examined how repeated ethanol administration during adolescence affects the brain after a period of abstinence and into adulthood. The team used advanced research techniques, including fiber photometry, chemogenetics, electrophysiology and Stimulated Emission Depletion (STED) microscopy, to examine the structure and function of astrocyte-synaptic interactions in the dorsal hippocampus.
Key Findings on Astrocyte-Synaptic Coupling
The researchers found that adolescent intermittent ethanol caused lasting structural and functional disruptions between astrocytes (搜索) and synapses, along with altered fear-related behavior in adulthood. Stimulating calcium signaling within astrocytes partially reduced the heightened fear response and increased the availability of gliotransmitters, rescuing important cell-to-cell communication critical for regulating communication in the brain.
The results suggest that astrocytes (搜索) may play a more significant role in the lasting effects of adolescent alcohol exposure than previously understood. While additional research is needed, the findings also raise the possibility that targeting astrocyte function could eventually offer a new approach for addressing some of the persistent behavioral effects associated with alcohol exposure and substance use.
Therapeutic Implications
"Growing evidence in recent years has highlighted a promising new role of astrocytes (搜索) in the modulation of synaptic activity and behavioral outcomes," said Olivia Coulter, first author of the paper and doctoral candidate at the Joan C. Edwards School of Medicine. "These cells contribute to the regulation of neurona function, influencing complex behaviors. Astrocytes are now being recognized as potential therapeutic targets for rescuing deficits associated with brain injury and mental health disorders. This work is an important step towards developing new astrocyte-targeted strategies to improve brain health."
The study, "Adolescent Alcohol Exposure Disrupts Astrocyte-Synaptic Structural and Functional Coupling in the Male Dorsal Hippocampus," was authored by Marshall researchers Risher, Coulter, Christopher D. Walker; Tristan Carter; Hannah G. Sexton; James Denvir, PhD; William C. Risher, PhD; and Brandon J. Henderson, PhD. The research was supported by grants from the Department of Veterans Affairs Biomedical Laboratory Research and Development, the National Institutes of Health, NASA West Virginia Space Grant Consortium, and the National Science Foundation.