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.

Endogenous metabolites play essential roles in the regulation of cellular identity and activity. Here we have investigated the process of oligodendrocyte precursor cell (OPC) differentiation, a process that becomes limiting during progressive stages of demyelinating diseases, including multiple sclerosis, using mass-spectrometry-based metabolomics. Levels of taurine, an aminosulfonic acid possessing pleotropic biological activities and broad tissue distribution properties, were found to be significantly elevated (~20-fold) during the course of oligodendrocyte differentiation and maturation. When added exogenously at physiologically relevant concentrations, taurine was found to dramatically enhance the processes of drug-induced in vitro OPC differentiation and maturation. Mechanism of action studies suggest that the oligodendrocyte-differentiation-enhancing activities of taurine are driven primarily by its ability to directly increase available serine pools, which serve as the initial building block required for the synthesis of the glycosphingolipid components of myelin that define the functional oligodendrocyte cell state.

The olfactory system has a rich cortical representation, including a large archicortical component present in most vertebrates, and in mammals neocortical components including the entorhinal and orbitofrontal cortices. Together, these cortical components contribute to normal odor perception and memory. They help transform the physicochemical features of volatile molecules inhaled or exhaled through the nose into the perception of odor objects with rich associative and hedonic aspects. This chapter focuses on how olfactory cortical areas contribute to odor perception and begins to explore why odor perception is so sensitive to disease and pathology. Odor perception is disrupted by a wide range of disorders including Alzheimer’s disease, Parkinson’s disease, schizophrenia, depression, autism, and early life exposure to toxins. This olfactory deficit often occurs despite maintained functioning in other sensory systems. Does the unusual network of olfactory cortical structures contribute to this sensitivity?