title: Lithium prevents long-term neural and behavioral pathology induced by early alcohol exposure.
abstract: Fetal alcohol exposure can cause developmental defects in offspring known as fetal alcohol spectrum disorder (FASD). FASD symptoms range from obvious facial deformities to changes in neuroanatomy and neurophysiology that disrupt normal brain function and behavior. Ethanol exposure at postnatal day 7 in C57BL/6 mice induces neuronal cell death and long-lasting neurobehavioral dysfunction. Previous work has demonstrated that early ethanol exposure impairs spatial memory task performance into adulthood and perturbs local and interregional brain circuit integrity in the olfacto-hippocampal pathway. Here we pursue these findings to examine whether lithium prevents anatomical, neurophysiological, and behavioral pathologies that result from early ethanol exposure. Lithium has neuroprotective properties that have been shown to prevent ethanol-induced apoptosis. Here we show that mice co-treated with lithium on the same day as ethanol exposure exhibit dramatically reduced acute neurodegeneration in the hippocampus and retain hippocampal-dependent spatial memory as adults. Lithium co-treatment also blocked ethanol-induced disruption in synaptic plasticity in slice recordings of hippocampal CA1 in the adult mouse brain. Moreover, long-lasting dysfunctions caused by ethanol in olfacto-hippocampal networks, including sensory-evoked oscillations and resting state coherence, were prevented in mice co-treated with lithium. Together, these results provide behavioral and physiological evidence that lithium is capable of preventing or reducing immediate and long-term deleterious consequences of early ethanol exposure on brain function.
authors.affiliation: Emotional Brain Institute, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA. Benjamin.Sadrian@nyumc.org
authors.forename: B
authors.initials: B
authors.lastname: Sadrian
authors.forename: S
authors.initials: S
authors.lastname: Subbanna
authors.forename: D A
authors.initials: DA
authors.lastname: Wilson
authors.forename: B S
authors.initials: BS
authors.lastname: Basavarajappa
authors.forename: M
authors.initials: M
authors.lastname: Saito
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000633:toxicity*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000517:prevention & control; D009473:Neuronal Plasticity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*
chemical_list: D002492:Central Nervous System Depressants; D018696:Neuroprotective Agents; D000431:Ethanol; D018021:Lithium Chloride