The evolution and distribution of morphological changes in the nervous system of the common marmoset following the acute administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
Six young adult marmosets received 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in multiple doses (total 8-16 mg/kg over 2-13 days) sufficient to produce a parkinsonian syndrome and were killed up to 3.5 months later. Cellular changes were found in the substantia nigra, ventral tegmental area, and hypothalamus. The earliest histological abnormalities were axonal swellings in proximal parts of nigrostriatal axons. Subsequent changes in the substantia nigra were reduced Nissl staining, reduced cell volume, and aggregation and loss of melanin granules. Other effects were reduced nuclear and nucleolar volumes, depletion of cells, and hyperplasia of glial cells. Shrunken cytoplasm and nuclei stained uniformly with eosin, and no cells showed cytoplasmic swellings or inclusions. These cellular alterations, with nuclear changes resembling karyolysis, do not occur in Parkinson's disease, which is characterised by Lewy body inclusions and signs of chromatolysis. The rapid appearance of axonal swellings, disruption of Nissl substance, and cell shrinkage suggest an insult to energy producing mechanisms. In this study, the absence of histological evidence of toxicity in the locus coeruleus and also in the substantia innominata and in serotonergic cell groups is unlike the more widespread degenerative changes of Parkinson's disease.
Gibb
W R
WR
Department of Neuropathology, National Hospitals for Nervous Diseases, Maida Vale, London.
Terruli
M
M
Lees
A J
AJ
Jenner
P
P
Marsden
C D
CD
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001369:Axons / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D002143:Callitrichinae; D003342:Corpus Striatum / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007031:Hypothalamus / Q000187:drug effects; D009434:Neural Pathways / Q000187:drug effects; D009457:Neuroglia / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D010302:Parkinson Disease, Secondary / Q000139:chemically induced*; D011725:Pyridines / Q000633:toxicity*; D013378:Substantia Nigra / Q000187:drug effects; D013787:Thalamic Nuclei / Q000187:drug effects
D011725:Pyridines; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine