PATTERN OF SYNAPTOPHYSIN IMMUNOREACTIVITY WITHIN MESENCEPHALIC GRAFTSFOLLOWING TRANSPLANTATION IN A PARKINSONIAN PRIMATE MODEL

The majority of investigations into the degree of restoration of neura l circuitry following transplantation of the embryonic ventral mesence phalon to the striatum have focused upon the particular neurochemical subtypes of the fibers exchanged between graft and host. Visualization of neurites of specific neurotransmitter type while informative regar ding the specificity of graft-host interactions, vastly underrepresent s overall synaptogenesis as it may occur in the grafting situation. Th e present approach of using a molecular marker characteristic of all n ormal, functional synapses provides broader information about the syna ptic remodeling that occurs after tissue grafting. Synaptophysin (SY), an integral membrane protein of the synaptic vesicle, is a reliable m arker of nerve terminal differentiation. Immunohistochemical staining with antibodies directed against SY and the dopamine synthetic enzyme tyrosine hydroxylase (TH) was used to assess overall synaptic differen tiation as well as the relationship between SY immunoreactivity and th e distribution of grafted dopamine (DA) neurons and processes in mesen cephalic grafts and mesencephalic-striatal co-grafts implanted in the striatum of MPTP-treated African green monkeys. Grafted embryonic cere bellar tissue was used as a comparison graft type that does not normal ly exchange prominent direct projections with striatum. Dense pericell ular arrays of SY-positive terminals were associated with TH-positive neurons in mesencephalic grafts. In mixed mesencephalic-striatal co-gr afts, TH-positive fiber patches within the striatal portion of the gra ft demonstrated a high degree of correspondence with SY immunoreactivi ty. In contrast, grafts of cerebellar tissue did not display the same pattern of prominent pericellular arrays of SY staining. These observa tions suggest that functional synapses are abundantly present within g rafted mesencephalon, and that these contacts are enriched in areas of the graft occupied by DA neurons. Implantation of an inappropriate st riatal target, the cerebellum, results in visibly diminished innervati on. The pattern of SY labeling observed suggests that tissue grafts ar e extensively innervated, probably both from extrinsic and intrinsic s ources, and that the pattern and density of this innervation correspon ds to the appropriateness of the graft-host interaction. (C) 1998 Else vier Science B.V.