Marina Guizzetti, Michelle Catlin, and Lucio G. Costa

Department of Environmental Health, University of Washington, Seattle, WA

Received 9/23/97 Accepted 10/2/97

2. INTRODUCTION

Offspring of alcoholics often present a syndrome (Fetal Alcohol Syndrome or FAS) whose principal features include central nervous system (CNS) dysfunctions (mental retardation, microencephaly, brain malformations), growth deficiency, and particular facial features (1). The CNS deficits of FAS appear to be long lasting, since recent studies have shown that they persist in young adults born with FAS, even if other symptoms (growth retardation, facial characteristics) have subsided (2-4). FAS is now considered a leading cause of mental retardation in the general population (5), and a recent report indicates that its incidence has increased over six-fold in the last 15 years, from 1 per 10,000 births in 1979 to 6.7 per 10,000 births in 1993 (6).

A large number of studies have been conducted in laboratory animals to gain an understanding of the characteristics and mechanisms of alcohol teratogenicity, and their results have been summarized in several books and reviews (7-10). In vivo studies in rodents have utilized both prenatal and postnatal exposures, to mimic human exposure during the first and early second trimester of pregnancy, and the late second and third trimester and early postnatal life, respectively. As the development of the nervous system differs across species (11), and since, within one species, different brain regions and cell types develop at different times, it has become apparent that the timing of exposure to ethanol is extremely important for specific adverse effects to be manifest. When ethanol is administered during the brain growth spurt (the first two postnatal weeks in the rat, characterized by proliferation of glial cells and maturations of neurons which develop dendrites, axons and synaptic contacts), the most striking effect observed is microencephaly (12), which is also seen in 80% of FAS children, and appears to be irreversible in both animals and humans (3,4,13,14).

The majority of studies aimed at exploring the neurologic sequelae resulting from alcohol abuse during pregnancy have focused on neuronal susceptibility. Several investigations have shown that exposure to ethanol can cause, for example, selective losses of hippocampal pyramidal cells or cerebellar Purkinje cells (15-17). A number of studies on the morphological and behavioral consequences of developmental exposure to ethanol have also been published, and will not be reviewed here. The extent to which glial cells, the intimate neighbors of neurons, are vulnerable to ethanol, has been much less investigated. Yet, in recent years, evidence has been accumulating that ethanol can significantly affect glial cells (18-20). A number of effects of ethanol on glial cells biochemistry and metabolism, morphology and differentiations have been found, and have been recently reviewed (20).

The present review will focus on the effects of ethanol on the proliferation of glial cells and will discuss the hypothesis that interference with this process may play a relevant role in the developmental neurotoxicity of alcohol.