Specific Reinnervation of Lesioned Mouse Striatum by Grafted Mesencephalic Dopaminergic Neurons

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Abstract
Selective lesions of the dopaminergic nigrostriatal system and embryonic neuron grafts were used to study the mechanism by which exogenous neurons can restore transmitter function and to examine CNS development and plasticity. C57BL mice treated with acetaldehyde/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine show irreversible loss of substantia nigra dopaminergic neurons. Implants of embryonic mesencephalic dopaminergic neurons functionally reinnervate the striatum and form a dense network of fibres; approximately 20% of the implanted dopaminergic cells survive for several months. However, dopaminergic fibre outgrowth and mesencephalic graft development appear lower in control, non-lesioned, animals. Moreover, implants of embryonic hypothalamic dopaminergic neurons show little or no survival. These results indicate that interactions between embryonic and adult neurons are selective. We suggest that this specificity may be sustained by the action of still unknown trophic and/or tropic factors, possibly produced by the lesioned striatum and by putative inhibitory mechanisms of cell migration and neuritic outgrowth.