On the altered expression of tyrosine hydroxylase and calbindin-D 28kD immunoreactivities and viability of neurons in the ventral tegmental area of Tsai following injections of 6-hydroxydopamine in the medial forebrain bundle in the rat

Calbindin-D 28kD is a calcium binding protein reported to protect neurons f rom degeneration by buffering intracellular calcium. It is expressed in mid brain dopaminergic neurons reported to be relatively resistant to degenerat ion in Parkinson's disease and certain of its animal models. Lesions of the nigrostriatal pathway produced in rats following injection of 6-hydroxydop amine result in a neurochemical profile similar to that seen in patients wi th Parkinson's disease. In the present study, brains were processed to exhi bit tyrosine hydroxylase- and calbindin-D 28kD immunoreactivities in sectio ns through the ventral mesencephalon at 3, 7, 10, 14 and 21 days after 6-hy droxydopamine had been injected into the medial forebrain bundle. Numbers o f ventral mesencephalic calbindin-D 28kD immunoreactive neurons were signif icantly reduced ipsilateral to the lesions at 3 days post-lesion and, follo wing slight recovery, remained significantly depleted through post-lesion d ay 21. The densities of calbindin-D 28kD and tyrosine hydroxylase immunorea ctive neurons were different only at the 3 day post-lesion time point, when the apparent loss of calbindin-D 28 kD immunoreactive profiles was signifi cantly greater. A lesion-induced increase in the proportion of neurons exhi biting both calbindin-D 28kD and tyrosine hydroxylase immunoreactivities, e xpected if calbindin-D 28kD is neuroprotective, was observed in the substan tia nigra, pars compacta, bur not in the ventral tegmental area. It is conc luded that, while the observed losses of tyrosine hydroxylase and calbindin -D 28kD immunoreactivities do not necessarily reflect neuronal degeneration , they are not consistent with CB confering a neuroprotective advantage in the ventral tegmental area following 6-OHDA lesions as administered in this study. (C) 2000 Elsevier Science B.V. All rights reserved.