Journal
NEURAL REGENERATION RESEARCH
Volume 15, Issue 8, Pages 1496-1501Publisher
WOLTERS KLUWER MEDKNOW PUBLICATIONS
DOI: 10.4103/1673-5374.274339
Keywords
adolescent; alcohol; astrocyte; astrocyte morphology; astrocyte-neuronal colocalization; CA1; gabapentin; GluA1; hippocampus; tripartite synapse
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Funding
- National Institute on Alcohol Abuse and Alcoholism (NIAAA) Neurobiology of Adolescent Drinking In Adulthood (NADIA) [2U01AA019925]
- National Institute on Alcohol Abuse and Alcoholism (NIAAA) [R00AA022651]
- National Institute on Drug Abuse (NIDA) [R01DA041455]
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Adolescent alcohol abuse is a substantive public health problem that has been the subject of intensive study in recent years. Despite reports of a wide range of effects of adolescent intermittent ethanol (AIE) exposure on brain and behavior, little is known about the mechanisms that may underlie those effects, and even less about treatments that might reverse them. Recent studies from our laboratory have indicated that AIE produced enduring changes in astrocyte function and synaptic activity in the hippocampal formation, suggesting the possibility of an alteration in astrocyte-neuronal connectivity and function. We utilized astrocyte-specific, membrane restricted viral labeling paired with immunohistochemistry to perform confocal single cell astrocyte imaging, three-dimensional reconstruction, and quantification of astrocyte morphology in hippocampal area CA1 from adult rats after AIE. Additionally, we assessed the colocalization of astrocyte plasma membrane labeling with immunoreactivity for AMPA-(alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) glutamate receptor 1, an AMPA receptor subunit and established neuronal marker of excitatory synapses, as a metric of astrocyte-synapse proximity. AIE significantly reduced the colocalization of the astrocyte plasma membrane with synaptic marker puncta in adulthood. This is striking in that it suggests not only an alteration of the physical association of astrocytes with synapses by AIE, but one that lasts into adulthood - well after the termination of alcohol exposure. Perhaps even more notable, the AIE-induced reduction of astrocyte-synapse interaction was reversed by sub-chronic treatment with the clinically used agent, gabapentin (Neurontin), in adulthood. This suggests that a medication in common clinical use may have the potential to reverse some of the enduring effects of adolescent alcohol exposure on brain function.
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