Neurology
http://www.massgeneral.org/ncs/neuro_faculty_Bhide.htm
Summary of Research
Key Researchers: Kiyomi Araki, Anju Vasudevan, Kumiko Fujimoto, Deirdre McCarthy
Our research is on brain development, especially on the role of the neurotransmitter dopamine in fundamental developmental processes such as neurogenesis, neuronal migration, axon growth, synapse formation and synaptic plasticity.
We discovered a novel role for dopamine in brain development by showing that dopamine receptor activation modulates neurogenesis and neuronal migration in the embryonic mouse brain. The two major types of dopamine receptors, D1- and D2-like receptors, produce opposite effects on neurogenesis and neuronal migration. Activation of the D1-like receptors decreases proliferation of precursor cells in the embryonic brain whereas activation of the D2-like receptors increases it. Similarly, activation of D1-like receptors promotes migration of GABA neurons from the basal forebrain to the dorsal forebrain whereas activation of the D2-like receptors decreases the migration.
We are also examining the way in which maternal cocaine abuse can perturb fetal brain development. We became interested in the effects of cocaine on the developing brain because cocaine tends to impair dopamine receptor signaling in the brain. We found recently that migration of GABA neurons from the basal forebrain to thee dorsal forebrain is decreased by exposure of the fetus to cocaine administered to the mother. We are now examining the way in which cocaine can impair brain development by impairing dopamine receptor signaling.
Our laboratory has developed transgenic mouse models in which dopamine receptor genes are over-expressed selectively in the CNS neuroepithelium or postmitotic neurons and electively, at specific periods of brain development. This mouse model is expected to help elucidate the long-term effects of transient imbalance in dopamine receptor signaling produced by therapeutic or illicit drugs on neuronal and glial cell development.
Contact Information
Phone: 617-726-5763
Fax: 617-726-6656
E-mail: pbhide@partners.org
