Ethanol alters astrocyte development: A study of critical periods using primary cultures

Abstract

Using astrocytes obtained from 21-day-old rat fetuses, in primary culture, we have analyzed the effect of prenatal alcohol consumption on DNA and protein synthesis of astrocytes during their development. The variation in sensitivity of astrocytes to ethanol "in vitro" during the proliferation and maturation periods was also assessed. Control astrocytes showed peaks of DNA and protein synthesis at 8 and 15 days, respectively. A significant decrease in both DNA and protein synthesis was found in astrocytes from fetuses prenatally exposed to ethanol. This effect on DNA synthesis was also observed when control astrocytes were exposed to ethanol (100 mM) "in vitro" during the entire culture period. The effects on astrocytes of short term (48h) exposure to ethanol during the proliferation or differentiation periods on the above mentioned parameters and on the cell cycle as well as the possible recovery from these effects were also evaluated. Decreases in DNA and protein synthesis were found in both periods. However, DNA synthesis and content were more affected in astrocytes exposed to ethanol during the proliferation period. This effect correlates with an accumulation of cells in the G0/G1 phase of the cell cycle. On the other hand, when cells exposed to ethanol were cultured in alcohol-free medium to assess recovery, only cells exposed to ethanol during days 4 to 6 still showed DNA ethanol-induced effects at 21 days. In conclusion, our results show that ethanol consumption during gestation induces serious damage to cortical astrocyte progenitor cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of Ethanol and Acetaldehyde Toxicity in Rat Astrocytes in Primary Culture

“…Ethanol has been shown to inhibit basal astroglial proliferation and response to mitogenic factors such as IGF-1 and acetylcholine (35,47 (49). High concentrations of ethanol alter cell-cycle kinetics of proliferating astrocytes by delaying the passage of the cells trough G1 (49). These effects appear to be dosedependent.…”

“…Proliferation of astrocytes is mainly controlled by soluble mitogenic factors such as growth factors acting on tyrosine kinase-coupled receptors (45,46). Ethanol has been shown to inhibit basal astroglial proliferation and response to mitogenic factors such as IGF-1 and acetylcholine (35,47 (49). High concentrations of ethanol alter cell-cycle kinetics of proliferating astrocytes by delaying the passage of the cells trough G1 (49).…”

Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse

“…Functional alterations in related circuits, including the central amygdala, frontal cortex, NAc, and bed nucleus of the stria terminalis (BNST) have been vigorously examined, and several molecular mechanisms have been implicated in the transition from acute to chronic alcohol consumption, including corticotropin-releasing factor (CRF), neuropeptide Y (NPY), and endogenous opioids (Mitchell et Although alcohol-induced effects on glia have not been as extensively characterized as its effects on neurons, accumulating evidence suggests that both microglia and astrocytes are impacted by acute and chronic alcohol. Early in vitro work with astrocyte progenitors cultured from fetal rat brains found that acute alcohol resulted in reduced GFAP expression in addition to stunted astrocyte cell proliferation (Guerri et al, 1990;Renau-Piqueras et al, 1989). In vivo, rats given free access to alcohol show increased activation of astrocytes (measured by GFAP) in discrete subregions of the hippocampus following shorter exposure periods (4-12 weeks), but decreased astrocyte activation was observed following extended drug access (36 weeks) (Franke, 1995).…”

Time-specific effects of ethanol exposure on cranial nerve nuclei: Gastrulation and neuronogenesis

“…The potential number of cycles depends on the length of the cell cycle and the number of days (or hours) during which neurons are generated. In the cerebral cortex (Miller, 1986;1988;Siegenthaler and Miller, 2005) and in primary cultures of astrocytes (Guerri et al, 1990;Luo and Miller 1999) or neurons (Jacobs and Miller, 2001), ethanol increases the length of the cell cycle. On the other hand, at least in the PSN (Miller and Muller, 1989), ethanol does not increase the period of neuronal generation.…”