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The Journal of Neuroscience, March 15, 1999, 19(6):2301-2312

A Glial Cell Line-Derived Neurotrophic Factor-Secreting Clone of the Schwann Cell Line SCTM41 Enhances Survival and Fiber Outgrowth from Embryonic Nigral Neurons Grafted to the Striatum and to the Lesioned Substantia Nigra

Martin J. Wilby¹, Simon R. Sinclair¹, Elizabeth M. Muir², Rike Zietlow^{1, 2}, Kathryn H. Adcock^{1, 2}, Philippe Horellou⁴, John H. Rogers², Stephen B. Dunnett^{1, 3}, and James W. Fawcett^{1, 2}

¹ Medical Research Council, Cambridge Centre for Brain Repair, The E. D. Adrian Building, University of Cambridge, Forvie Site, Robinson Way, Hills Road, Cambridge CB2 2PY, United Kingdom, ² Physiological Laboratory, University of Cambridge, Downing Site, Cambridge CB1 3EG, United Kingdom, ³  Department of Experimental Psychology, University of Cambridge, Downing Site, Cambridge CB2 3EG, United Kingdom, and ⁴ C 9923 Centre National de la Recherche Scientifique, Laboratoire de Genetique Moleculaire de la Neurotransmission et des Processus Degeneratifs, Hopital de la Pitie Salpetriere, Batiment CERVI, 75013 Paris, France.

We have developed a novel Schwann cell line, SCTM41, derived from postnatal sciatic nerve cultures and have stably transfected a clone with a rat glial cell line-derived neurotrophic factor (GDNF) construct. Coculture with this GDNF-secreting clone enhances in vitro survival and fiber growth of embryonic dopaminergic neurons. In the rat unilateral 6-OHDA lesion model of Parkinson's disease, we have therefore made cografts of these cells with embryonic day 14 ventral mesencephalic grafts and assayed for effects on dopaminergic cell survival and process outgrowth. We show that cografts of GDNF-secreting Schwann cell lines improve the survival of intrastriatal embryonic dopaminergic neuronal grafts and improve neurite outgrowth into the host neuropil but have no additional effect on amphetamine-induced rotation. We next looked to see whether bridge grafts of GDNF-secreting SCTM41 cells would promote the growth of axons to their striatal targets from dopaminergic neurons implanted orthotopically into the 6-OHDA-lesioned substantia nigra. We show that such bridge grafts increase the survival of implanted embryonic dopaminergic neurons and promote the growth of axons through the grafts to the striatum.

Key words: bridge graft; GDNF; Parkinson's disease; 6-OHDA; Schwann cells; SCTM41; substantia nigra; neuronal graft

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Copyright © 1999 Society for Neuroscience  0270-6474/99/1962301-12$05.00/0

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