Microglia easily can become activated, and the initial stages of activation are characterized by the secretion of signaling molecules, slight morphological changes, and increased production of molecules involved in immune responses (i.e., major histocompatibility complex [MHC]) as well as of TLRs (Graeber 2010). Activation of microglia and astrocytes also increases proinflammatory agents, including TNFα, that alter the transmission of nerve signals (i.e., neurotransmission), including signal transmission mediated by the excitatory neurotransmitter glutamate. Likewise, studies have suggested that alcoholism is related to excessive glutamate levels (i.e., a hyperglutamate state). In the outer layer of the brain (i.e., the cerebral cortex), chronic alcohol-induced neuroimmune activation leads to a hyperglutamate state that reduces cortical function (figure 2). One mechanism contributing to this hyperglutamate state involves TNFα, which acts to reduce the activity of glutamate transporters2 in the astrocytes (Zou and Crews 2005). Similarly, beverage alcohol (i.e., ethanol) has been shown to inhibit glutamate transport (Zou and Crews 2006). This blockade of glutamate transporters increases glutamate levels outside the cells and particularly in the space between two neurons where nerve signals are transmitted (i.e.,
