Embryonic dopaminergic neuron transplants in MPTP lesioned mouse striatum.
The aim of this work is to study CNS development and plasticity, and to study the mechanisms that allow exogenous embryonic dopaminergic neurons to restore transmitter function in the experimental parkinsonism. Recently, we have developed a new method that produces a selective degeneration of the dopaminergic nigrostriatal system in mice by a combined acetaldehyde/MPTP treatment. This procedure results in a selective and irreversible loss of substantia nigra dopaminergic neurons in C57BL mice, while other dopaminergic areas of the brain are spared. MPTP alone results instead only in a temporary, reversible damage of nigro- striatal dopaminergic functions. Embryonic dopaminergic neurons from ventral mesencephalon or hypothalamus are implanted in lesioned or normal right striata or lateral ventricles. The mesencephalic neurons implanted in a lesioned host form a dense network of fibers which establish functional reinnervation of the striatum (or caudate-putamen complex). After several months about the entire striatal parenchyma appears reinnervated; on average, 20% of the grafted mesencephalic dopaminergic cells survive. Implants of embryonic HYP neurons instead, show little or no survival. Moreover, dopaminergic mesencephalic neurons in control non-lesioned animals show a poor development with little fiber outgrowth. These data indicate that interactions between embryonic dopaminergic neurons and adult striatal neurons is specific. They also suggest that this specificity is sustained by trophic and/or tropic factors possibly produced by the lesioned striatum and by putative inhibitory mechanisms of cell migration and neuritic outgrowth.
Istituto Internazionale di Genetica e Biofisica, CNR, Naples, Italy.
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Di Porzio
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Zuddas
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D016380:Brain Tissue Transplantation; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D016332:Fetal Tissue Transplantation; D007031:Hypothalamus / Q000196:embryology / Q000637:transplantation; D008297:Male; D008636:Mesencephalon / Q000196:embryology / Q000637:transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000637:transplantation; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine