Sherrel S. Howard

Laboratory Address:
48-149 NPI
Los Angeles, CA 90095

Office Address:
48-228A NPI
Los Angeles, CA 90095

Research Description:

My laboratory has made the important observation that dopamine (DA) receptors are expressed in oligodendrocytes at two stages during their differentiation, suggesting that the receptor has a non-synaptic, possibly trophic function in non-neuronal cells. We are presently examining the hypothesis that the DA receptor/s play a regulatory role in either myelination, the primary biological function of oligodendrocytes, and/or the differentiation of these glial cells. A second hypothesis is that different DA receptor isotypes are expressed at different stages during oligodendrocyte differentiation, leading to regulation of myelin formation. We propose to establish which of the various DA receptor isotypes are expressed in oligodendrocytes and the stage(s) of differentiation at which this expression occurs. Evidence in favor of these hypotheses comes from work we have published in which we have:

1. identified the DA D2r in a subset of mature oligodendrocytes in vivo
2. identified the DA D3 receptor in immature oligodendrocytes and their precursors in vitro and
3. observed that if the D3r is chronically stimulated in vitro by a DA agonist, there appears to be an increase in oligodendrocytes precursors in the cultures at later times and there is a substantial drop in the percentage of mature oligodendrocyutes elaborating membrane sheets.

These studies are particularly relevant in defining the effect of CNS development in pups exposed to drugs of abuse during the perinatal period, as we can now demonstrate a reduction in myelination after cocaine exposure. Further studies may also provide insight into ways of enhancing myelin formation in hypomyelination diseases.