Biological studies on alcohol-induced neuronal damage.

Alcohol is a well-known cytotoxic agent which causes various kinds of neuronal damage. In spite of thousands of published studies, the true mechanism of alcohol-induced neuronal damage remains unclear. Neurogenesis is the generation of neurons from neural stem cells (NSCs) and occurs in predominantly two regions of the brain, the subventricular zone and the dentate gyrus of the hippocampus. NSCs are the self-renewing, multipotent precursor cells of neurons, astrocytes, and oligodendrocytes in the central nervous system. Recent studies have begun to illuminate the role of neurogenesis in the biological and cellular basis of psychiatric disorders and several clinical symptoms seen in alcoholism such as depression, cognitive impairment, underlying stress and brain atrophy have been linked to impaired neurogenesis. Heavy alcohol consumption decreases neurogenesis in animals, while in vitro studies have shown decreased generation of new neurons after alcohol exposure. These findings suggest that decreased neurogenesis is important in the pathophysiology of alcoholism. Neurogenesis can be divided into four stages; proliferation, migration, differentiation and survival. Our in vitro studies on NSCs showed that alcohol decreased neuronal differentiation at doses lower than those that affected cell survival and suggested that neuron-restrictive silencer factor, or repressor element-1 silencing transcription factor (NRSF/REST) could be involved in alcohol-induced inhibition of neuronal differentiation. In an animal model of fetal alcohol effects behavioral symptoms improved after NSC transplantation. Neurogenesis could be the target for new strategies to treat alcohol related disorders.