Differential effects of suicide transport lesions of the striatonigral or striatopallidal pathways on subsets of striatal neurons.
In the basal ganglia, centrally active suicide transport agents produce apparently selective lesions of the striatopallidal and striatonigral pathways based on receptor binding and neuropeptide mRNA studies. In the present study we sought to determine the selectivity of suicide transport lesions for specific subsets of striatal neurons. Using immunohistochemical methods, the neostriata of adult rats were examined 10 days after an injection of volkensin into the substantia nigra or an injection of OX7-saporin into the globus pallidus. Ricin, a suicide transport agent active in the peripheral but not the central nervous system, was injected into each target as a control. Adjacent sections were processed for (1) Nissl stain to assess neuronal density, both overall and for large interneurons, (2) NADPH-diaphorase (NADPH-d) histochemistry, to mark medium-sized aspiny interneurons, (3) enkephalin immunocytochemistry, to label striatopallidal neurons, or (4) substance P immunocytochemistry, to label striatonigral neurons. Ricin injections produced no change in the densities of these subsets of striatal cells. In animals receiving volkensin or OX7-saporin injections, analyses of Nissl material revealed that the striata ipsilateral to the toxin injections appeared normal and did not exhibit shrinkage or gliosis; however, a quantitation analysis revealed a moderate decrease in cell density (12-16% loss, P < 0.01). The densities of both large and NADPH-d-containing striatal interneurons were unchanged after lesions in either target. Following nigral injections with volkensin, the density of striatal substance P-labeled cells decreased (26% loss, P < 0.01), while the density of enkephalin-labeled cells did not decrease significantly (11% decrease, P > 0.1). After pallidal injections with OX7-saporin, the density of striatal enkephalin-labeled cells decreased (20% loss, P < 0.01), while that of substance P-labeled cells remained unchanged. These data show that nigral volkensin and pallidal OX7-saporin injections differentially lesion striatonigral and striatopallidal projection neurons and spare striatal interneurons. This study provides further evidence for the selectivity, specificity, and utility of suicide transport agents to study brain structure and function.
Roberts
R C
RC
Maryland Psychiatric Research Center, Baltimore 21228.
Harrison
M B
MB
Francis
S M
SM
Wiley
R G
RG
D000818:Animals; D000911:Antibodies, Monoclonal; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004745:Enkephalins / Q000378:metabolism; D005917:Globus Pallidus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006023:Glycoproteins; D018796:Immunoconjugates; D007150:Immunohistochemistry; D000922:Immunotoxins / Q000008:administration & dosage / Q000633:toxicity*; D008845:Microinjections; D009699:N-Glycosyl Hydrolases; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009498:Neurotoxins; D037121:Plant Lectins; D010940:Plant Proteins / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D054789:Ribosome Inactivating Proteins, Type 1; D054790:Ribosome Inactivating Proteins, Type 2; D012276:Ricin / Q000008:administration & dosage / Q000633:toxicity; D000076985:Saporins; D013373:Substance P / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D000911:Antibodies, Monoclonal; D004745:Enkephalins; D006023:Glycoproteins; D018796:Immunoconjugates; D000922:Immunotoxins; D009498:Neurotoxins; C085346:OX7-saporin; D037121:Plant Lectins; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D054790:Ribosome Inactivating Proteins, Type 2; D013373:Substance P; D012276:Ricin; C049134:volkensin; D009252:NADPH Dehydrogenase; D009699:N-Glycosyl Hydrolases; D000076985:Saporins