Cholinergic differentiation factor/leukemia inhibitory factor enhances functional effects of adrenal medulla grafts...

We recently found that adrenal medulla grafts implanted into the hippocampus of rats survived for several months and significantly decreased the deficits produced by hippocampal lesions in the radial maze test [Jousselin-Hossaja et al. (1994) Neuroscience 59, 275-284]. These grafts contained choline acetyltransferase immunopositive chromaffin cells and received cholinergic innervation. In the experiments reported here, adrenal medulla grafts implanted in lesioned hippocampus were treated with cholinergic differentiation factor/leukemia inhibitory factor. In the presence of this factor, the number of chromaffin cells with cholinergic phenotypes increased as well as the beneficial effects of the grafts on the performances of rats in the radial maze. These results suggest that the functional effects of adrenal medulla grafted into the hippocampus set into play cholinergic mechanisms. The cholinergic differentiation factor/leukemia inhibitory factor may also have facilitated the survival and recovery of cholinergic neurons in the host tissue. However, due to the large range of action of this cytokine and the richness of the adrenal medulla contents, non cholinergic factors are also probably involved. Our results may help to elucidate the functions of the cholinergic differentiation factor/leukemia inhibitory factor since they provide the first indication that its intracerebral injection may have behavioral effects. Moreover, our data confirm the possibility of improving the efficiency of adrenal medulla implants in the central nervous system by appropriate treatments, not only by facilitating survival but also by selectively amplifying some potential factors of the graft. This might greatly enlarge the field of this grafting technique for analysing the normal functioning of the brain and for repairing it.