Menschena21kursbuchpdf747
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menschena21kursbuchpdf747 menschena21kursbuchpdf747non-neuronal cells are an important component of neuronal function and dysfunction. they synthesize and secrete neurotransmitters, and modulate neurotransmission via autocrine, paracrine and juxtacrine mechanisms. they also release neurotransmitters (e.g., glutamate, adenosine, dopamine) and modulators (e., nitric oxide, atp) to modulate neuronal activity. their presence or absence can profoundly affect the properties of a neuronal circuit and may contribute to disease pathogenesis. the cerebellar granule cells are a classic example of a neuronal circuit that is critically dependent on the presence of non-neuronal cells. in fact, granule cell dysfunction is a hallmark of several neurological disorders and a causal factor in epileptogenesis and cognitive deficits. the non-neuronal cells in the cerebellum, the bergman glia, play critical roles in cerebellar function. this proposal is a request for a continuation of a cobre program directed at the study of glial biology in the cerebellum. the overarching goal of this proposal is to understand the molecular and cellular mechanisms that regulate glial cell development, differentiation and function in the cerebellum. we have developed an in vitro model system that allows us to characterize the molecular and cellular mechanisms of bergman glial development, differentiation and function. this model system employs the p19c6 murine teratocarcinoma cells, which differentiate into bergman glia in the presence of retinoic acid. thus, the molecules involved in cerebellar development can be studied at multiple levels: 1) the biochemical mechanisms by which retinoic acid is used to initiate p19c6 differentiation into bergman glia, 2) the molecular basis of p19c6 differentiation into bergman glia, 3) the biochemical and molecular mechanisms by which these glial cells interact with other neurons and non-neuronal cells in the cerebellum, and 4) the biochemical and molecular mechanisms by which these glial cells regulate the activity of neurons in the cerebellum. we have already characterized the retinoic acid-induced differentiation of p19c6 cells into bergman glia. we have also determined that bergman glia express the components of the glutamatergic system, and that these glia modulate the activity of cerebellar neurons in a manner that is dependent upon the expression of glutamate receptors. finally, we have shown that the bergman glia release atp, and that the atp release is modulated by a protein we have named cerebellin-1. collectively, these data support a role for atp in the regulation of cerebellar function. the experiments proposed in this application will test the hypothesis that bergman glia play an important role in the regulation of cerebellar function. // this.setstate({selected:!this.state.selected}); this.
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