Medial-to-lateral gradient of neostriatal NGF receptors: relationship to cholinergic neurons and NGF-like immunoreactivity.
High-affinity binding sites for recombinant human NGF (rhNGF) were studied in the caudate-putamen of the adult rat and rabbit. Displaceable 125I-rhNGF binding sites were densely distributed throughout the caudate-putamen and were 2-3-fold more prevalant in the ventrolateral and lateral than in the medial caudate-putamen. The amount of nondisplaceable binding did not vary throughout the caudate-putamen. The medial-to-lateral receptor gradient was correlated (r = +0.99) with a 2-3-fold medial-to-lateral increase in ChAT activity. In contrast, NGF-like immunoreactivity (NGF-LI) was prevalent but uniformly distributed in the caudate-putamen. Lesions of intrinsic cholinergic neurons by quinolinic acid produced extensive gliosis in the medial, central, and lateral caudate-putamen, yet 125I-rhNGF binding was decreased in each of these regions. The activity of ChAT and 125I-rhNGF binding throughout the caudate-putamen were each decreased by 40% following quinolinic acid. Binding was not changed after 70-77% dopamine nerve terminal depletions induced by 6-hydroxydopamine, demonstrating a nonglial, nondopaminergic locus for striatal NGF binding sites. The cholinergiclike topography of NGF binding sites throughout the intact caudate-putamen, the parallel decreases of cholinergic neurons and NGF binding sites following intrinsic neuronal loss, and the uniform neostriatal gradient of NGF-LI are consistent with the trophic role of endogenous NGF for cholinergic interneurons of the caudate-putamen.
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Developmental Biology, Genentech, Incorporated, South San Francisco, California 94080.
Dugich-Djordjevic
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Armanini
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Bakhit
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D000818:Animals; D001667:Binding, Competitive; D002421:Caudate Nucleus / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000032:analysis; D003342:Corpus Striatum / Q000033:anatomy & histology / Q000166:cytology / Q000378:metabolism*; D004298:Dopamine / Q000502:physiology; D018492:Dopamine Antagonists; D006892:Hydroxydopamines / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008454:Mazindol / Q000378:metabolism; D009414:Nerve Growth Factors / Q000032:analysis / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D016627:Oxidopamine; D011699:Putamen / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor; D011994:Recombinant Proteins / Q000378:metabolism
D018492:Dopamine Antagonists; D006892:Hydroxydopamines; D009414:Nerve Growth Factors; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D017475:Receptors, Nerve Growth Factor; D011994:Recombinant Proteins; D016627:Oxidopamine; D008454:Mazindol; D002795:Choline O-Acetyltransferase; D004298:Dopamine