Alcohol Exposure Alters the Expression Pattern of Neural Cell Adhesion Molecules During Brain Development

Abstract

Neural cell adhesion molecules (NCAMs) play critical roles during development of the nervous system. The aim of this study is to investigate the possible effect of ethanol exposure on the pattern of expression and sialylation of NCAM isoforms during postnatal rat brain development because alterations in NCAM content and distribution have been associated with defects in cell migration, synapse formation, and memory consolidation, and deficits in these processes have been observed after in utero alcohol exposure. The expression of NCAM isoforms in the developing cerebral cortex of pups from control and alcohol-fed mothers was assessed by western blotting, ribonuclease protection assay, and immunocytochemistry. The highly sialylated form of NCAM [polysialic acid (PSA)-NCAM] is mainly expressed during the neonatal period and then is down-regulated in parallel with the appearance of NCAM 180 and NCAM 140. Ethanol exposure increases PSA-NCAM levels during the neonatal period, delays the loss of PSA-NCAM, decreases the amount of NCAM 180 and NCAM 140 isoforms, and reduces sialyltransferase activity during postnatal brain development. Neuraminidase treatment of ethanol-exposed neonatal brains leads to more intense band degradation products, suggesting a higher content of NCAM polypeptides carrying PSA in these samples. However, NCAM mRNA levels are not changed by ethanol. Immunocytochemical analysis demonstrates that ethanol triggers an increase in PSA-NCAM immunolabeling in the cytoplasm of astroglial cells, accompanied by a decrease in immunogold particles over the plasma membrane. These findings indicate that ethanol exposure during brain development alters the pattern of NCAM expression and suggest that modification of NCAM could affect neuronal-glial interactions that might contribute to the brain defects observed after in utero alcohol exposure. Key Words: Ethanol-Brain development-Neural cell adhesion molecules-Sialyltransferase-Astroglial cells. J. Neurochem. 75, 954 -964 (2000).

Ethanol impairs monosaccharide uptake and glycosylation in cultured rat astrocytes

“…Indeed, ethanol decreases the production and release of growth factors and the intracellular and plasma membrane levels of the highly sialylated form of the neural cell adhesion molecule (PSA-NCAM) in astrocytes (Miñana et al 2000). However, these effects may be the synergic result of alterations in the glycosylation process and the cytoskeletal components that participate in the intracellular traffic.…”

“…Incubation time was 60 min at 37°C. After two 10-min rinses in 0.1% BSA-Tris buffer and a rinse in redistilled water, the sections were air-dried and finally counterstained with uranyl acetate and lead citrate (Renau-Piqueras et al 1989;Miñana et al 2000). Quantitative analysis of gold particle distribution on Golgi apparatus areas was carried out using stereological methods (Renau-Piqueras et al 1987, 1997.…”

“…Glial cells are also sensitive to alcohol, suggesting that perturbations in the neuron-glia interactions account for the alcohol-induced developmental defects of the brain (Guerri and RenauPiqueras 1997;Renau-Piqueras et al 1998;Guerri et al 2001). In addition, chronic alcohol consumption and prenatal alcohol exposure alters the glycosylation process in rat hepatocytes, neurons and astroglial cells (Vallés et al 1994;Renau-Piqueras et al 1987, 1997Kim and Druse 1996;Miñana et al 2000). This may inhibit or delay the intracellular transport of nascent glycoproteins and glycolipids in the cell or else alter the expression of membrane proteins.…”

“…This may inhibit or delay the intracellular transport of nascent glycoproteins and glycolipids in the cell or else alter the expression of membrane proteins. Thus, both prenatal alcohol exposure and alcohol treatment in vitro affect the cell membrane glycoproteins and the expression of neurotrophic factor receptors, decrease the synthesis and constitutive release of growth factors, and alter the intracellular and plasma membrane levels of the highly sialylated form of the neural cell adhesion molecule (PSA-NCAM) in cultured rat astrocytes (Vallés et al 1994;Kim and Druse 1996;Miñana et al 2000).…”

Aniracetam Reversed Learning and Memory Deficits Following Prenatal Ethanol Exposure by Modulating Functions of Synaptic AMPA Receptors

“…Alternatively, optimal levels of neural cell adhesion molecules (eg, NCAM and L1) play an important role in stable synapse formation (Edelman and Chuong, 1982). It has been shown that perinatal ethanol exposure alters the pattern of NCAM and L1 expression, inhibiting the formation of new synapses (Minana et al, 2000;Bearer, 2001). Prenatal ethanol exposure reduces neuronal numbers (Perez et al, 1991) with less elaborate dendritic arbors, fewer dendritic spines (Smith and Davies, 1990;Abel et al, 1983;Ferrer et al, 1988;Perez et al, 1991), and decreased vesicle number per area of synaptic contact zones (Lolova et al, 1989) in the CA1 hippocampus.…”