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Transplantation of neuronal progenitors into the central nervous system (CNS) offers great promise for the treatment of neurological disorders such as epilepsy. Recent reports of multipotent neural “stem” or progenitor cells with ability to disperse and differentiate into neurons in adult CNS have further raised expectations that defective brain circuits can be repaired. Findings from the Alvarez-Buylla laboratory recently demonstrated that transplantation of progenitor cells from the embryonic medial ganglionic eminence (MGE) results in cells that disperse, migrate and differentiate into morphologically identifiable neurons in multiple adult brain regions. MGE cells in the host brain express ?-aminobutyric acid (GABA), the primary inhibitory neurotransmitter. Based on these observations, we proceeded to demonstrate that transplanted MGE cells integrate as new GABAergic interneurons, modulate the overall level of excitability in a host brain and potentially act as a “cure” for patients with intractable forms of epilepsy. In an on-going collaboration among the Alvarez-Buylla, Rubenstein and Baraban laboratories at UCSF we recently showed that transplanted MGE precursors functionally enhance inhibitory synaptic transmission in the host brain (Alvarez-Dolado et al. 2006). Demonstration of a functional change in cortical inhibition following transplantation is a necessary first step toward the development of an appropriate clinical treatment utilizing stem cells. In current studies, we are testing whether the transplantation and generation of new inhibitory neurons reduces seizure activity in a variety of rodent epilepsy models.
Selected Publications
Cobos IM, Calcagnotto ME, Vilaythong AJ, Thwin MT, Noebels JL, Baraban SC, Rubenstein JLR: Mice lacking the Dlx1 transcription factor exhibit subtype-specific loss of interneurons, reduced synaptic inhibition and epilepsy. Nature Neuroscience 8:1059-1068, 2005.
Alvarez-Dolado M, Calcagnotto ME, Karkar KM, Southwell DG, Jones-Davis DM, Estrada RC, Rubenstein JLR, Alvarez-Buylla A, Baraban SC. Cortical inhibition modified by embryonic neural precursors grafted into the postnatal brain. Journal of Neuroscience 26:7380-7390, 2006.
Baraban SC. Emerging epilepsy models: insights from mice, flies, worms and fish. Current Opinion in Neurology 20:164-168, 2007.
Information last updated April 2007
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