FUNCTIONAL IMPAIRMENT OF NIGROSTRIATAL NEURONS PROGRESSES FOLLOWING WITHDRAWAL OF 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE

C57 BL/6 mice were rendered severely parkinsonian by exposure to high doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The fluorescent retrograde tracer Fast Blue was injected into the neostriatum one (gr oup A) or five weeks (group B) following exposure to 1-methyl-4-phenyl -1,2,3,6-tetrahydropyridine. Neurons located in the substantia nigra p ars compacta and in the centre median-parafascicular complex were anal ysed. There was no variation in the number and distribution of Fast Bl ue-labelled perikarya located in the centre median-parafascicular comp lex, which are insensitive to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyri dine. No variation was seen in the number of Nissl-stained perikarya l ocated in the substantia nigra pars compacta, indicating that neurons had not degenerated. The number and the density of Fast Blue retrograd ely-labelled neurons located in the same region were decreased in grou p A by 41% and in group B by 55%. Fast Blue labelling provided a measu re of functional impairment in viable neurons. The Fast Blue-to-Nissl cell ratio was 55% in controls and declined to 20% in group A and to 1 7% in group B mice. The present study shows that (i) functional inacti vation of Viable neurons can be measured by using a fluorescent retrog rade tracer following exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine and (ii) inactivation of retrograde axonal transport progress es from one to five weeks following withdrawal of the toxin. Fluoresce nt retrograde probes may be used to measure the anatomical substrate o f recovery induced by drugs or by brain grafts in parkinsonian animals . Copyright (C) 1996 IBRO. Published by Elsevier Science Ltd.