Disappearance of GAD-mRNA and tyrosine hydroxylase in substantia nigra following striatal ibotenic acid lesions: evidence for transneuronal regression.
Transneuronal regression in substantia nigra reticulata (SNR) and substantia nigra compacta (SNC) neurons was studied in Fischer 344 male rats by immunocytochemistry and by in situ hybridization. Three months after striatal lesioning by ibotenic acid, there was a shrinkage (30%) of the SNR region cross-sectional area and a 50% disappearance of neurons that contain glutamic acid decarboxylase (GAD)-mRNA, but only in the ventromedial portion of this nucleus. Loss of dopaminergic neurons, as recognized by tyrosine hydroxylase immunoreactivity, occurred only in caudal portions of the SNC and SNR. These findings suggest that lesions in reciprocally connected pathways, like the nigrostriatal and striatonigral systems, may produce a vicious cycle (feedforward cascade) of neurodegeneration due to interference with retrograde ana anterograde influences.
Pasinetti
G M
GM
Ethel Percy Andrus Gerontology Center, Department of Biological Sciences, University of Southern California, Los Angeles 90089-0191.
Morgan
D G
DG
Finch
C E
CE
D000818:Animals; D001284:Atrophy; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D007839:Functional Laterality; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D005968:Glutamate Decarboxylase / Q000235:genetics*; D007051:Ibotenic Acid / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D009928:Organ Specificity; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013378:Substantia Nigra / Q000033:anatomy & histology / Q000187:drug effects / Q000201:enzymology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D007051:Ibotenic Acid; D014446:Tyrosine 3-Monooxygenase; D005968:Glutamate Decarboxylase