Neuropathological study on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine of the crab-eating monkey

Experimental parkinsonism was induced by systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the crab-eating monkey (Macaca fascicularis). In the acute stage, the substantia nigra showed necrotic nerve cells, extracellular release of pigment granules and histiocytic infiltration. The nerve cells underwent vacuolation of the cytoplasm with chromatin clumping of the nucleus and disintegration of the nucleolus. The striking feature was the presence of variously-shaped inclusion bodies within abnormal mitochondria which sometimes disclosed a distortion of the cristae. Golgi apparatus and endoplasmic reticulum were also dilated. In the locus ceruleus swollen nerve cells were observed with vacuolated cytoplasm and pyknotic nucleus where expanded mitochondria also contained the inclusions. Some of the inclusion bodies are probably insoluble precipitations due to inhibition of mitochondrial oxidation by a certain metabolite of MPTP. In the protracted stage the substantia nigra revealed a considerable loss of the nerve cells associated with melanophagia and astrocytic proliferation. A few surviving nerve cells showed an increased number of Golgi apparatus and rough endoplasmic reticula, and the presence of autophagosomes, dense bodies and intra-mitochondrial inclusion. These changes are interpreted as being a part of the reparative process from the cellular damage.