CO-TRANSPLANTATION OF FETAL LATERAL GANGLIONIC EMINENCE AND VENTRAL MESENCEPHALON CAN AUGMENT FUNCTION AND DEVELOPMENT OF INTRASTRIATAL TRANSPLANTS

Methods to increase the development and sustained function of embryoni c mesencephalic dopamine cells after transplantation into dopamine (DA )-depleted striatum are currently under investigation, Elements that a re crucial for the maturation and connectivity of neurons during norma l development of the brain way also play a role in the development and integration of grafted embryonic tissue. Based on in vitro and in viv o observations of the enhancing effects of striatal tissue on nigral d opaminergic cell development and survival, we demonstrate that inclusi on of embryonic striatal cells, specifically from the lateral ganglion ic eminence (LGE), produces dopaminergic transplants with augmented fu nctional effects. Rats neonatally DA-depleted and co-transplanted with embryonic nigral and LGE cells developed improved functional outcome when compared with animals receiving only nigral cells, and they requi red the transplantation of fewer nigral cells to produce a strong beha vioral effect, Anatomically, the inclusion of LGE cells produced incre ased DA cell survival, a higher density of reinnervation into the DA-d epleted host striatum, and patches of DA fibers within the co-transpla nts, There were also an increased number of host striatal cells which induced the immediate-early gene c-fos in co-transplanted animals comp ared to animals receiving nigral cells alone, indicating a higher degr ee of host-cell activation. The ability to enhance function, cell surv ival, reinnervation, and host activation with nigral-striatal co-trans plants in the presence of fewer nigral cells supports the hypothesis o f a trophic influence of striatal cells on nigral DA cells. (C) 1997 A cademic Press.