This is an investigation of the selective sprouting of dopaminergic neurons induced by embryonic brain grafts. There is little neuronal regrowth following 6-hydroxydopamine lesions of neurons in the medial forebrain bundle (mfb) in the absence of grafts of embryonic neocortical tissue. If such grafts are implanted within two weeks of creating the lesion, catecholaminergic neurons sprout through the lesion over the next 2 months. Grafts made into intact mfbs show both tyrosine hydroxylase (TH) and dopamine--hydroxylase (DH) activity in sprouting fibers but those implanted into lesioned areas, TH activity was unchanged while DH activity was significantly reduced. Neuroreceptor autoradiography was used to confirm that dopamine transporter sites were contained in patches of the graft while norepinephrine transporters could not be located there. Thus, these embryonic grafts promote selective sprouting of dopaminergic neurons in contrast to adrenergic or noradrenergic neurons. This suggests the presence of a dopamine neuron-specific trophic factor within the graft. These finding have important implications for the treatment of Parkinson's disease using brain grafts. Results in humans have indicated that the efficacy of fetal substantia nigra implants is far superior to results observed with adrenal medullary grafting. While these observations might be due to sprouting of the graft dopaminergic neurons, the data described above suggest the possibility of a trophic factor in the brain graft which might promote growth of the host's own dopaminergic neurons. If such factors could be identified, it might eliminate the need for tissue transplantation in the effective treatment of Parkinson's disease.
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