SELECTIVE HIPPOCAMPAL-LESIONS DIFFERENTIALLY AFFECT THE PHENOTYPIC FATE OF TRANSPLANTED NEURONAL PRECURSOR CELLS

RN33B cells, a CNS-derived neuronal precursor cell line, transplanted into normal adult rat hippocampus can survive and morphologically diff erentiate with their ultimate morphology dependent on the integration site. This study examined the differentiation and structural integrati on of RN33B cells transplanted into the lesioned adult hippocampus. Py ramidal neurons of the CA1-3 regions or granular neurons in the dentat e gyrus were preferentially destroyed by unilateral intraventricular k ainic-acid or intradentate colchicine injections, respectively. One we ek after the lesion, a suspension of undifferentiated beta-galactosida se (beta-gal)-labeled RN33B cells was stereotaxically transplanted int o the lesioned or the contralateral hippocampus. After 5-7 weeks, sect ions of the recipient brains were analyzed by toluidine blue staining and immunohistochemistry for beta-gal, GFAP, and OX-42, A reactive gli osis was observed on the lesioned side which persisted up to 7 weeks p ostlesion (the latest time point examined). RN33B cells survived in th e lesioned hippocampus and assumed variable morphologies depending on the hippocampal layer into which they integrated. Only RN33B cells loc ated in intact or partially damaged cell layers or in the unlesioned c ontralateral hippocampus differentiated with morphologies similar to t hose of endogenous neurons characteristic of those layers. Cells locat ed in layers completely depleted of endogenous neurons assumed bipolar morphologies or sent out multiple processes with no structural polari ty, unlike the neuronal morphologies characteristically seen in intact hippocampal cell layers. These data suggest that the presence of some endogenous neurons and partially conserved cytoarchitectural organiza tion are essential for immortalized neuroepithelial precursor cells to differentiate into region-specific neuronal cell types. (C) 1996 Acad emic Press, Inc.