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Enduring alterations in hippocampal astrocytesynaptic proximity following adolescent alcohol exposure: reversal by gabapentin

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Neural Regeneration Research 2020年第8期15卷 1496-1501页

作者： Kati L.Healey Sandra Kibble Sierra Hodges Kathryn J.Reissner Anze Testen Tiffany A.Wills Shawn K.Acheson Benjamin M.Siemsen john a.mcfaddin Michael D.Scofield H.Scott Swartzwelder Department of Psychiatry and Behavioral Sciences Duke University Medical CenterDurhamNCUSA Department of Psychology and Neuroscience University of North CarolinaChapel HillNCUSA Department of Cell Biology and Anatomy LSU School of MedicineNew OrleansLAUSA Department of Anesthesia and Perioperative Medicine Medical University of South CarolinaCharlestonSCUSA

Adolescent alcohol abuse is a substantive public health problem that has been the subject of intensive study in recent *** 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 *** 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 *** 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 ***,we assessed the colocalization of astrocyte plasma membrane labeling with immunoreactivity for AMPA-(α-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 *** significantly reduced the colocalization of the astrocyte plasma membrane with synaptic marker puncta in *** 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 *** 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 *** 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 *** animal experiments conducted were approved by the Duke University Institutional Animal Care and Use Committee(Protocol

关键词： adolescent alcohol astrocyte astrocyte morphology astrocyte-neuronal colocalization CA1 gabapentin GluA1 hippocampus tripartite synapse

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