cytological effects of a neurotrophic peptide [MPF] in Parkinsonian rats

ABSTRACT

Substantia nigra [SN] samples from rats with 6-hydroxdopamine [6-OHDA] -induced lesions of right nigrostriatal pathways were retrieved and examined by transmission electron microscopy [TEM] 15-17 months after a single intrastriatal injection of a metabolically-stable analogue of Lys-Lys-Gly-Glu [MPF] in Krebs-Hensleitt buffer, given two weeks after the lesioning. The results were compared with those from control samples taken from rats which had been similarly lesioned and kept for 15-17 months, but which had received only Krebs-Hensleitt buffer, and with samples taken from two age matched, non-lesioned rats. Compared with the age matched, non-lesioned rats, there was a 37% overall loss of and extensive damage to all surviving SN neurons in samples from control rats [lesioned, buffer only]. There was widespread collapse of mitochondria [63% in the case of dopaminergic neurons], loss of cell membranes [in 4.4% of cases], myelin abnormalities [9.0%] and increased vacuolation [10.9%]. In contrast, most of the SN neurons from MPF-treated rats were healthy reflected in a high degree of cellular organization and integration; only 9.0% of the mitochondria were collapsed, and the cell membranes damage [2.9%] myelin abnormalities [1.5%], and the increased vacuolation [2.6%] were significantly less than found in the control rats. We have previously reported a significant reduction in the amphetamine-induced turning behaviour of lesioned rats following injection of the MPF analogue, beginning 6 weeks after the MPF injection, and reaching marked and consistent levels after 12 weeks. This time course, in conjunction with the present results and known neurotrophic properties of MPF, suggest that the favourable behavioural effects of MPF arise by restoration of nigrostriatal pathways