Role of MCP-1 and CCR2 in alcohol neurotoxicity.

Abstract

Alcohol abuse causes profound damage to both the developing brain and the adult brain. Prenatal exposure to alcohol results in a wide range of deficits known as fetal alcohol spectrum disorders (FASD). Alcohol abuse in adults is associated with brain shrinkage, memory and attention deficits, communication disorders and physical disabilities. Monocyte chemoattractant protein-1 (MCP-1/CCL2) is one of the key chemokines that regulate the recruitment and activation of monocytes and microglia. Both MCP-1 and its receptor C-C chemokine receptor type 2 (CCR2) expressed in the brain are involved in various neuroinflammatory disorders, such as multiple sclerosis (MS), Alzheimer's disease (AD) and Parkinson's disease (PD). However, the role of MCP-1/CCR2 in alcohol-induced brain damage is unclear. Recent evidence indicates that alcohol exposure increased the activity of MCP-1/CCR2 in both mature and developing central nervous systems (CNS). MCP-1/CCR2 signaling in the brain was involved in alcohol drinking behavior. MCP-1/CCR2 inhibition alleviated alcohol neurotoxicity by reducing microglia activation/neuroinflammation in the developing brain and spinal cord. In this review, we discussed the role of MCP-1/CCR2 signaling in alcohol-induced neuroinflammation and brain damage. We also discussed the signaling cascades that are involved in the activation of MCP-1/CCR2 in response to alcohol exposure.