Further Investigations on the Mechanisms Involved in Intrastriatal Mesencephalic Grafts in the Rat, with Special Reference to Dopamine-Neuropeptide Y Interactions
A number of transplantation studies on an animal model for Parkinson’s disease bearing a 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal dopaminergic pathway were carried out since the late 70’s (Björklund and Stenevi, 1979, Perlow et al., 1979). Implanting foetal dopamine (DA) neurons into the striatum of these rats was found to alleviate some Parkinson’s disease like symptoms in the DA deficient recipients. In rats with unilateral lesion, motor impairments such as drug-induced rotational asymmetry were found to be completely abolished after DA grafts, while in more complex conditioned behavior tests, rats remained severely impaired (Björklund et al., 1987). Despite these limitations, human foetal ventral mesencephalic tissue has been implanted into the brain of Parkinsonian patients with variable success. Although there is some ambiguity in the statement that brain grafts can have functional effects, because it contains spontaneously active neurons and releases neurotransmitter, or because it may trigger some adaptive behavioral responses in the host animals, the cellular mechanisms whereby ventral mesencephalic transplants act need to be exactly determined for research on neural transplantation to be able to progress.
KeywordsDopamine Tyrosine Neurol Catecholamine Acetylcholine
Unable to display preview. Download preview PDF.
- Becker, J.B., and Ariano, M.A., 1991, Behavioral effects of fetal substantia nigra tissue grafted into the dopamine-denervated striatum:responses to selective D1 and D2 dopamine receptor agonists, Rest. Neurol. Neurosci. 3:187–195Google Scholar
- Chritin, M., Savasta, M., Mennicken, F., Bal, A., Abrous, D.N., Le Moal, M., Feuerstein, C, and Herman, J.P., 1992, Intrastriatal dopamine-rich implants reverse the increase of dopamine D2 receptor mRNA levels caused by lesion of the nigrostriatal pathway:a quantitative in situ hybridization study, Eur. J. Neurosci. 4:663–672.PubMedCrossRefGoogle Scholar
- Clarke, D. J., Brundin, P., Strecker, R. E., Nilsson, O. G., Björklund, A., and Lindvall, O., 1988, Human fetal dopamine neurons grafted in a rat model of Parkinson’s disease:Ultrastructural evidence for synapse formation using tyrosine hydroxylase immunocytochemistry, Exp. Brain Res. 73:115–126.PubMedCrossRefGoogle Scholar
- Daszuta, A., Moukhles, H., Forni, C, Dusticier, N., Nieoullon A., 1992, Regulation of dopamine release as monitored by in vivo voltammetry in intrastriatal grafts of fetal mesencephalon neurons, Rest. Neurol. Neurosci. 4:15P32.Google Scholar
- Forni, C, Brundin, P., Strecker, R.E., El Ganouni, S., Björklund, A., and Nieoullon A., 1989, Time-course of recovery of dopamine neuron activity during reinnervation of denervated striatum by fetal mesencephalic grafts as assessed by in vivo voltametry, Exp. Brain Res. 76:75–87.PubMedCrossRefGoogle Scholar
- Kerkerian-Le Goff, L., Salin, P., Vuillet, J., and Nieoullon, A., 1991, NeuropeptideY neurons in the striatal network. Functional adaptive responses to impairment of striatal inputs, in: “The Basal Ganglia III,” G. Bernardi, M.B. Carpenter, G. Di Chiara, M. Morelli and P. Stanzione, eds., Plenum Press, New York, pp. 49–61.Google Scholar
- Manier, M., Abrous, D.N., Feuerstein, C, Le Moal, M., and Herman, J.P., 1991, Increase of striatal methionin enkephalin content following lesion of the nigrostriatal dopaminergic pathway in adult rats and reversal following the implantation of embryonic dopaminergic neurons:a quantitative immunohistochemical analysis, Neuroscience 42:427–439.PubMedCrossRefGoogle Scholar
- Moukhles, H., Amalric, M., Nieoullon, A., Daszuta, A., 1992a, Partial recovery of sensorimotor deficits in a conditioned task induced by mesencephalic cells grafted to locally dopamine deafferented striatum in the rat, Rest. Neurol, and Neurosci. 15P30.Google Scholar
- Nishino, H., Hashitani, T., and Kumazaki, M., 1991, Grafting of catecholaminergic cells in the mammalian brain and reconstruction of disturbed function:basic problems to be solved, J. Comp. Biochem. Physiol. 98:211–220.Google Scholar
- Nishino, H., Hashitani, T., Kumazaki, M., Sato H, Furuyama F., Isobe Y., Watari N., Kanai M., and Shiosaka S., 1990, Long-term survival grafted cells, dopamine synthesis/release, synaptic connections, and functional recovery after transplantation of fetal nigral cells in rats with unilateral 6-OHDA lesions in the nigrostriatal dopamine pathway, Brain Res. 534:83–93.PubMedCrossRefGoogle Scholar
- Zetterström, T., Brundin, P., Gage, F.H., Sharp, T., Isacson, O., Dunnett, S.B., Ungerstedt, U., and Björklund, A., 1986, In vivo measurement of spontaneous release and metabolism of dopamine from intrastriatal nigral grafts using intracerebral dialysis, Brain Res. 362:344–349.PubMedCrossRefGoogle Scholar