Systemic administration of MPTP induces thalamic neuronal degeneration in mice.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a known neurotoxicant primarily selective for catecholaminergic neurons, including those of the nigrostriatal dopaminergic system, thereby mimicking the pathology 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 additional sites of MPTP-induced neuronal degeneration in mice. Male CD-1 mice received a single 50 mg/kg dose of MPTP intraperitoneally at room temperature or at a reduced temperature (6 degrees C), which has been shown to potentiate striatal dopamine depletion. Neuronal degeneration was observed in the substantia nigra pars compacta (SN), ventral tegmental area (VTA) and retrorubral field (RRF) of only animals dosed in the low temperature environment. Neuronal degeneration was also observed in other catecholaminergic nuclei in both treatment groups. In addition, degenerating cell bodies and fibers were detected in the midline and intralaminar thalamic nuclei of all dosed animals, regardless of the dosing environment. Pharmacological manipulations which prevented nigral degeneration (deprenyl and nomifensine pretreatment) also prevented the degeneration of thalamic neurons. MK-801 pretreatment, however, resulted in a disproportionate protection of the thalamic neurons. These findings confirm and extend our previous observations regarding 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.
Freyaldenhoven
T E
TE
Division of Neurotoxicology, National Center for Toxicological Research, Jefferson, AR 72079-9502, USA.
Ali
S F
SF
Schmued
L C
LC
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D015259:Dopamine Agents / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009410:Nerve Degeneration; D009474:Neurons / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D009627:Nomifensine / Q000494:pharmacology; D012642:Selegiline / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology; D013696:Temperature; D013788:Thalamus / Q000187:drug effects* / Q000473:pathology*
D015259:Dopamine Agents; D018696:Neuroprotective Agents; D009627:Nomifensine; D012642:Selegiline; D016291:Dizocilpine Maleate; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine