Enduring alterations in hippocampal astrocyte-synaptic proximity following adolescent alcohol exposure: reversal by gabapentin
Kati L. Healey1
Sandra Kibble1
Sierra Hodges1
Kathryn J. Reissner2
Anze Testen2
Tiffany A. Wills3
Shawn K. Acheson1
Benjamin M. Siemsen4
John A. McFaddin4
Michael D. Scofield4
H. Scott Swartzwelder1
1.Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA2.Department of Psychology and Neuroscience, University of North Carolina, Chapel Hill, NC, USA3.Department of Cell Biology and Anatomy, LSU School of Medicine, New Orleans, LA, USA4.Department of Anesthesia and Perioperative Medicine, Medical University of South Carolina, Charleston, SC, USA
摘要：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 as-trocyte-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-(α-amino-3-hydroxy-5-methyl-4-isoxaz-olepropionic 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 sug-gests 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-in-duced 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. All animal experiments conducted were approved by the Duke University Institutional Animal Care and Use Committee (Protocol Registry Number A159-18-07) on July 27, 2018.
机标关键词：
分类号：R453(治疗学)R364(病理学)R749(精神病学)
论文发表日期：2020-08-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：6( 1496-1501 )
英文信息