SYSTEMIC ADMINISTRATION OF MPTP INDUCES THALAMIC NEURONAL DEGENERATION IN MICE

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a known neuroto xicant primarily selective for catecholaminergic neurons, including th ose of the nigrostriatal dopaminergic system, thereby mimicking the pa thology of Parkinson's disease (PD). In this study, serial transbrain sectioning, followed by staining with a newly developed fluorochrome ( Fluoro-Jade) specific for degenerating neurons, was used to detect add itional sites of MPTP-induced neuronal degeneration in mice. Male CD-1 mice received a single 50 mg/kg dose of MPTP intraperitoneally at roo m temperature or at a reduced temperature (6 degrees C), which has bee n shown to potentiate striatal dopamine depletion. Neuronal degenerati on was observed in the substantia nigra pars compacta (SN), ventral te gmental area (VTA) and retrorubral field (RRF) of only animals dosed i n the low temperature environment. Neuronal degeneration was also obse rved in other catecholaminergic nuclei in both treatment groups. In ad dition, degenerating cell bodies and fibers were detected in the midli ne and intralaminar thalamic nuclei of all dosed animals, regardless o f the dosing environment. Pharmacological manipulations which prevente d nigral degeneration (deprenyl and nomifensine pretreatment) also pre vented the degeneration of thalamic neurons. MK-801 pretreatment, howe ver, resulted in a disproportionate protection of the thalamic neurons . These findings confirm and extend our previous observations regardin g the protective effect of hyperthermia in CD-1 mice and also suggest that regions of the thalamus may be relevant to the pathophysiology of PD. (C) 1997 Elsevier Science B.V.