Expression of transforming growth factor‐β in developing rat cerebral cortex: Effects of prenatal exposure to ethanol

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Abstract
The effects of prenatal ethanol exposure on the spatiotemporal expression of transforming growth factor‐β (TGFβ) and its receptors in developing rat cerebral cortex in vivo were examined. Pregnant Long‐Evans rats were fed ad libitum with a diet containing ethanol from gestational day (G) 6 through G21 or were pair fed an isocaloric nonalcoholic liquid diet. A quantitative immunoblotting study showed that expression of TGFβ ligands was differentially affected by ethanol; ethanol decreased TGFβ1 expression fetally and in the mature cortex and increased TGFβ2 at most ages. A complementary immunohistochemical experiment generated similar results so far as the timing of ligand expression was concerned. In both control and ethanol‐treated rats, TGFβ1 was expressed by cells in the two neocortical proliferative zones and neurons in the cortical plate. TGFβ2 was expressed principally by radial glia and astrocytes in developing rats. In the adult, both ligands were expressed by glia and neurons. Ethanol virtually eliminated the TGFβ1 expression in the perinatal subventricular zone. The TGFβ2‐positive radial glial labeling was transient and was lost earlier in ethanol‐treated neonates than in controls. Concomitantly, the appearance of TGFβ2‐positive glia occurred earlier in the ethanol‐treated rats. The expression of only one receptor (TGFβIr) was affected by ethanol; it was increased during the pre‐ and early postnatal periods. TGFβIr was expressed by glia perinatally and by all cell types in weanlings. As with TGFβ2, ethanol exposure promoted the loss of TGFβIr expression in radial glia and the precocious expression among astrocytes. TGFβIIr was expressed primarily by neurons. Thus, TGFβ ligands and receptors are strategically placed both in time and space to regulate cell proliferation and migration. Ethanol, which affects both of these processes, has marked effects on the TGFβ system and apparently promotes the early transformation of radial glia into astrocytes. J. Comp. Neurol. 460:410–424, 2003.