title: Synaptic plasticity in the hippocampus shows resistance to acute ethanol exposure in transgenic mice with astrocyte-targeted enhanced CCL2 expression.
abstract: It has been shown that ethanol exposure can activate astrocytes and microglia resulting in the production of neuroimmune factors, including the chemokine CCL2. The role of these neuroimmune factors in the effects of ethanol on the central nervous system has yet to be elucidated. To address this question, we investigated the effects of ethanol on synaptic transmission and plasticity in the hippocampus from mice that express elevated levels of CCL2 in the brain and their non-transgenic littermate controls. The brains of the transgenic mice simulate one aspect of the alcoholic brain, chronically increased levels of CCL2. We used extracellular field potential recordings in acutely isolated hippocampal slices to identify neuroadaptive changes produced by elevated levels of CCL2 and how these neuroadaptive changes affect the actions of acute ethanol. Results showed that synaptic transmission and the effects of ethanol on synaptic transmission were similar in the CCL2-transgenic and non-transgenic hippocampus. However, long-term potentiation (LTP), a cellular mechanism thought to underlie learning and memory, in the CCL2-transgenic hippocampus was resistant to the ethanol-induced depression of LTP observed in the non-transgenic hippocampus. Consistent with these results, ethanol pretreatment significantly impaired cued and contextual fear conditioning in non-transgenic mice, but had no effect in CCL2-transgenic mice. These data show that chronically elevated levels of CCL2 in the hippocampus produce neuroadaptive changes that block the depressing effects of ethanol on hippocampal synaptic plasticity and support the hypothesis that CCL2 may provide a neuroprotective effect against the devastating actions of ethanol on hippocampal function.
authors.affiliation: Molecular and Integrative Neuroscience Department, SP30-1522, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Bray
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Reyes
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Roberts
authors.forename: Richard M
authors.initials: RM
authors.lastname: Ransohoff
authors.forename: Donna L
authors.initials: DL
authors.lastname: Gruol
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D000431:Ethanol / Q000008:administration & dosage*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D000431:Ethanol