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Neurobiology

Where to Graft Neurons

Transplanting neurons directly inside damaged areas of the brain restores lost neuronal networks in mice, and might lead to better recovery than current grafting procedures. This raises hope for patients with neurodegenerative disorders.

Because the central nervous system is incapable of regenerating neurons when its circuits are damaged, neurodegenerative disorders like Parkinson’s disease lead to irreversible deficits in motor skills, with devastating outcomes. One of the approaches used to overcome this incapacity is to transplant embryonic neurons inside the patients’ brains.
Currently, the transplantation procedure consists in grafting cells not inside the damaged areas per se, but in “target regions”–i.e., regions where the patient’s original neurons used to send their projections before the damage. In patients with Parkinson’s disease, for instance, embryonic neurons are grafted inside the striatum (target region) rather than in the substantia nigra, which is the region where neurons are damaged. “It has always been stipulated that transplanted neurons cannot grow long extensions in the adult brain and must therefore be grafted inside target regions,” says Mohamed Jaber, from IPBC1 in Poitiers. But such transplants only lead to partial motor recovery, “probably due to the ectopic localization of the transplant–away from its original site,” says Jaber.

neurone

© A. Gaillard, M. Jaber, A. Cantreau

When neurons are grafted in the damaged area, they produce long extensions (green) toward the host target.




Researchers thus started investigating the possibility of grafting neurons directly inside damaged areas. Currently, a study2 led by Afsanelh Gaillard, from Jaber’s laboratory, provides the first evidence that transplants inside damaged regions grow very long and specific extensions, and re-establish damaged neuronal networks–something that never occurs when grafts are made inside target regions.  
In their experiments, the researchers used embryonic cortical neurons from transgenic mice expressing a green fluorescent protein. They transplanted fluorescent neurons inside the damaged motor cortex of adult mice. “This way, we were able to distinguish between the transplanted cells and the hosts’ cells,” says Jaber. The authors observed that the transplanted neurons were able to send projections as far as original neurons would have, and, most importantly, that they reached the appropriate target sites, including distant ones such as the spinal cord, where they formed synaptic connections with host cells. “Not only did they emit projections at very far distances, but they were also very organized and specific,” says Jaber. “But this only worked if the neurons transplanted were of the same type as the original neurons of the damaged region. If you transplant another type, the extensions will not reach the target you are aiming for.”
Does this translate into greater motor recovery? The question has yet to be answered, and the team now plans to reproduce its experiments in monkeys and quantify functional recovery. “Placing the transplant in the appropriate location should help rewire the damaged brain circuitry and better restore normal behavior,” concludes Jaber.
Clémentine Wallace

Notes :

1. Institut de Physiologie et Biologie Cellulaires, (CNRS / Université de Poitiers).
2. A. Gaillard et al., “Reestablishment of damaged adult motor pathways by grafted embryonic cortical neurons,” Nature Neuroscience. 10: 1294-99. 2007.

Contacts :

Mohamed Jaber
IPBC, Poitiers.
Mohamed.Jaber@univ-poitiers.fr


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