The development of cerebral cortical astrocytes will be studied in cultures from mice with three copies (aneuploidy) of chromosome 16 (MMU 16; Ts16). Astrocytes have been increasingly implicated in hormonal control of brain development and may possess some of the membrane excitability mechanisms normally characteristic of neurons. The long term objectives are to determine the developmental consequences of autosomal trisomy in mammals. Astrocyte morphology, expression of glial specific antigens such as glial fibrillary acidic protein (GFAP), and expression of voltage-gated ion channels as determined by tracer influx and radiolabeled ligand binding measurements will be used to establish the state of astrocyte differentiation. Conversion to a stellate morphology of GFAP+ cells and appearance of voltage-gated sodium channels with high affinity for saxitoxin are associated with astrocyte maturation in vitro. Preliminary results reveal that this developmental program is accelerated in Ts16 Astrocytes. The proposed studies will investigate the nature of this acceleration maturation in Ts16 astrocytes and also examine whether growth factors trigger this premature aging. These studies should provide new information about the roles of astrocytes and neuronal-glial interactions in normal brain development and how astrocyte development is altered by aneuploidy.
