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The Journal of Neuroscience, November 8, 2006, 26(45):11532-11539; doi:10.1523/JNEUROSCI.2688-06.2006

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Development/Plasticity/Repair
Neural Cell Adhesion Molecule L1-Transfected Embryonic Stem Cells Promote Functional Recovery after Excitotoxic Lesion of the Mouse Striatum

Christian Bernreuther,^1,2 * Marcel Dihné,^1 * Verena Johann,³ Johannes Schiefer,³ Yifang Cui,¹ Gunnar Hargus,¹ Janinne Sylvie Schmid,¹ Jinchong Xu,^1,4 Christoph M. Kosinski,³ and Melitta Schachner¹

¹Zentrum für Molekulare Neurobiologie Hamburg, University of Hamburg, D-20251 Hamburg, Germany, ²Institute for Neuropathology, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg, Germany, ³Neurology Center, University Medical Center Rheinisch-Westfälische Technische Hochschule-Aachen, D-52074 Aachen, Germany, and ⁴Sino-German Center for Neuroscience, Dalian University Medical School, Dalian, Liaoning 116027, China

Correspondence should be addressed to Dr. Melitta Schachner, Zentrum für Molekulare Neurobiologie Hamburg, Falkenried 94, D-20251 Hamburg, Germany. Email: melitta.schachner{at}zmnh.uni-hamburg.de

We have generated a murine embryonic stem cell line constitutively expressing L1 at all stages of neural differentiation to investigate the effects of L1 overexpression on stem cell proliferation, migration, differentiation, cell death, and ability to influence drug-induced rotation behavior in an animal model of Huntington's disease. L1-transfected cells showed decreased cell proliferation in vitro, enhanced neuronal differentiation in vitro and in vivo, and decreased astrocytic differentiation in vivo without influencing cell death compared with nontransfected cells. L1 overexpression also resulted in an increased yield of GABAergic neurons and enhanced migration of embryonic stem cell-derived neural precursor cells into the lesioned striatum. Mice grafted with L1-transfected cells showed recovery in rotation behavior 1 and 4 weeks, but not 8 weeks, after transplantation compared with mice that had received nontransfected cells, thus demonstrating for the first time that a recognition molecule is capable of improving functional recovery during the initial phase in a syngeneic transplantation paradigm.

Key words: neural cell adhesion molecule L1; embryonic stem cell; neuronal differentiation; quinolinic acid; striatum; functional recovery

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Received June 10, 2005; revised Sept. 11, 2006; accepted Sept. 11, 2006.

Correspondence should be addressed to Dr. Melitta Schachner, Zentrum für Molekulare Neurobiologie Hamburg, Falkenried 94, D-20251 Hamburg, Germany. Email: melitta.schachner{at}zmnh.uni-hamburg.de

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