IBCN   20355
INSTITUTO DE BIOLOGIA CELULAR Y NEUROCIENCIA "PROFESOR EDUARDO DE ROBERTIS"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
EFFECTS OF PRENATAL ETHANOL EXPOSURE ON RADIAL GLIA CELLS AND POSTMITOTIC NEUROBLASTS MIGRATION IN THE FETAL CEREBRAL CORTEX
Autor/es:
ARONNE MP, GUADAGNOLI T, EVRARD SG, BRUSCO HA.
Lugar:
San Diego
Reunión:
Congreso; Frontiers in Addiction Research: 2010 NIDA Mini-Convention; 2010
Institución organizadora:
NIDA
Resumen:
The fetal alcohol syndrome (FAS) represents a public health issue associated with maternal alcohol abuse during pregnancy. Central nervous system (CNS) developmental defects, which can lead to microcephaly and mental retardation, are among the most significant characteristics of FAS. Different types of cortical dysplasias have been proved to occur after prenatal ethanol exposure (PEE) due to, among other factors, disorders in the migration of postmitotic neuroblasts (Miller, 1986). Although the maturation of the cerebral cortex (CC) is completed on the postnatal period under the influence of environmental stimuli, most of its gross architecture is assembled prenatally and crucially involves the orderly migration of postmitotic neuroblasts from the proliferative ventricular zone (VZ), at the inner surface of the telencephalon, through the overlying intermediate zone to the cortical plate (Angevine and Sidman, 1961; Rakic, 1974). Neuroblasts, the precursors of neurons, migrate mainly attached to the cellular processes of radial glia cells (RGCs) by using them as a living scaffolding. During corticogenesis, RGCs perform a dual function: they behave as precursor cells (Choi et al., 1978; Levitt et al., 1981; Misson et al., 1991) and as migratory substrates for neuroblasts (Rakic, 1972; Hatten et al., 1990). They express vimentin, a cytoskeletal protein, a type III intermediate filament (Pixley et al., 1984; Alberts et al., 2007). Moreover, by the end of neurogenesis and during neuroblasts migration, RGCs seem to transform gradually into astrocytes in some regions such as the CC (Pixley et al., 1984; Voigt, 1989). When RGCs change their fenotype to astrocytes they stop expressing vimentin and begin to express glial fibrillary acidic protein (GFAP; another type III intermediate filament) with an overlapping period when they express both (Bignami and Dahl, 1974; Voigt, 1989). As mature astrocytes do, RGCs also express S-100b protein, a dimeric neurotrophic and neurite outgrowth-promoting protein with many important actions during both pre- and postnatal life. Among these multiple functions, S-100b acts as a promoter of cytoskeletal stabilization (Huttunen et al., 2000; Donato, 2003). The correct specification of RGCs is therefore essential for a normal corticogenesis to occur (Pinto-Lord et al., 1982).                 Pax6, a transcription factor, member of the Paired (Pax) family of genes, has been shown to control brain and developmental aspects of many other organs (Chi et al., 2002; Buckingham et al., 2007). Pax6 is also known to be localized in RGCs and to control its differentiation in the CC (Götz et al, 1998; Simpson and Price, 2002). In the absence of a functional Pax6, cortical RGCs exhibit altered morphology, cell number and cell-cycle kinetics (Götz et al, 1998). We have previously shown in a recent paper, for the first time in a mammalian species, that high blood ethanol concentrations (BECs; 119->300 mg/dl), attained through intraperitoneal (i.p.) injections, were able to alter Pax6 expression during cortical development (Aronne et al., 2008).                  Postmitotic neuroblasts migrating through RGCs processes express doublecortin (DCX), a type of microtubule-associated protein (MAP) that regulates microtubule stability and influences the cytoskeleton dynamic state (Horesh et al., 1999). DCX is widely expressed in migrating neurons during prenatal and postnatal development in the CNS and during adult neurogenesis, as well (Gleeson et al., 1999).                 Thus, it has been extensively proven that the cytoskeleton is substantially altered under the influence of PEE (see Evrard and Brusco, 2010 for a comprehensive review). We have shown previously in other studies of our laboratory that the cytoskeletal proteins of both neurons and glia are altered after a PEE under both low (Ramos et al., 2002; Evrard et al., 2003, 2006) and high BECs (Aronne et al., 2008). The aim of our present work was to evaluate, in a mammalian model of PEE, the action of moderate BECs, when EtOH is given to rats by means of a liquid diet (a way certainly more physiological than i.p. injections). Specifically, we have studied here the EtOH actions under these experimental conditions on different proteins expressed by RGCs (vimentin and S-100b) and by migrating neuroblasts (DCX) in order to assess the important corticogenetical diad of RGCs-migrating neuroblasts, a relationship known to be altered during brain development in PEE offspring. We have also aimed at study the actions of moderate BECs on the expression levels of the important Pax6 transcriptional factor given that high BECs were previously shown to alter its expression levels in the developing rat brain (Aronne et al., 2008).