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Reestablishment of damaged adult motor pathways by grafted embryonic cortical neurons

Abstract

Damage to the adult motor cortex leads to severe and frequently irreversible deficits in motor function. Transplantation of embryonic cortical neurons into the damaged adult motor cortex was previously shown to induce partial recovery, but reports on graft efferents have varied from no efferent projections to sparse innervation. Here, we grafted embryonic cortical tissue from transgenic mice overexpressing a green fluorescent protein into the damaged motor cortex of adult mice. Grafted neurons developed efferent projections to appropriate cortical and subcortical host targets, including the thalamus and spinal cord. These projections were not a result of cell fusion between the transplant and the host neurons. Host and transplanted neurons formed synaptic contacts and numerous graft efferents were myelinated. These findings demonstrate that there is substantial anatomical reestablishment of cortical circuitry following embryonic cortex grafting into the adult brain. They suggest that there is an unsuspected potential for neural cell transplantation to promote reconstruction after brain injury.

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Figure 1: Distribution of GFP graft efferents toward host targets.
Figure 2: Mean number of labeled fibers in control, motor-to-motor and visual-to-motor cases.
Figure 3: FISH analysis and retrograde labeling on brain sections of adult male mice transplanted with female GFP embryos.
Figure 4: Maturation indices of the transplant.
Figure 5: Synaptic contacts between the transplant and the host.

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Acknowledgements

We thank M. Okabe for the GFP mice, B. Zalc for the PLP antibody, P. Gaspar, F. Nothias and M. Solinas for critically reading the manuscript, and G. Raymond for continuous support. We thank B. Merceron for technical assistance, M. Decresac for help with the confocal microscopy and F. Gaillard for help with statistical analysis. This work was supported by the CNRS, Poitiers University, France Parkinson (2003), Fondation de l'Avenir (2005 and 2006), Institut de France (2005), and Région Poitou Charentes (2003 and 2006).

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A.G. carried out most of the experiments, designed and carried out the study, sought funding, and wrote the manuscript. L.P. carried out the FISH studies, B.D. carried out the electron microscopy studies, A.C. carried out the analysis on the confocal microscope, F.M. carried out the FACS analysis. M.R. initially designed the study and is now retired. M.J. designed and supervised the study, sought funding, and wrote the manuscript.

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Correspondence to Afsaneh Gaillard.

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Gaillard, A., Prestoz, L., Dumartin, B. et al. Reestablishment of damaged adult motor pathways by grafted embryonic cortical neurons. Nat Neurosci 10, 1294–1299 (2007). https://doi.org/10.1038/nn1970

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