Myelin basic protein-mRNA used to monitor trimethyltin neurotoxicity in rats.
Trimethyltin (TMT) is an alkyltin that targets neurons of the limbic system. A gene probe (i.e., mRNA) for myelin basic protein (MBP), a major component of central nervous system myelin, was used to monitor this toxic neuropathy in Sprague-Dawley rats. Animals were administered a single intraperitoneal injection of TMT-hydroxide at a neuropathic (8.0 mg/kg/body wt) or nonneuropathic (0.8 mg/kg/body wt) dose and sampled at 1, 3, or 7 days postexposure to correlate the progression of hippocampal neuropathology with probe (i.e., MBP-mRNA) levels. Microscopic examination of the brain showed only moderate but progressive damage over the 7-day postexposure period in animals treated with the neuropathic dose. Neuronal loss was first observed in the dendate gyrus and CA4 at 1 day postexposure, and progressed to the CA3c sector at 3 and 7 days postexposure. Elsewhere in the brain, minimal involvement of the entorhinal cortex neurons occurred 3 days postexposure and intensified by 7 days. No histological damage was seen at the nonneuropathic (0.8 mg/kg) dose. For gene probe analysis, the brain was divided into anterior and posterior halves. In rats treated with the neuropathic dose of TMT, the anterior brain showed progressive depressions of MBP-mRNA levels over the 1-, 3-, and 7-day postexposure period that correlated with increasing hippocampal neuropathology. The posterior brain showed no significant changes in MBP-mRNA levels with respect to that of controls over the same time period. At the nonneuropathic dose (0.8 mg/kg) a significant depression of MBP-mRNA levels occurred in the anterior brain at 7 days postexposure in the absence of overt histological damage.
Veronesi
B
B
U.S. Environmental Protection Agency, Health Effects Research Laboratories, Research Triangle Park, North Carolina 27711.
Pringle
J
J
Mezei
C
C
D000818:Animals; D015152:Blotting, Northern; D015342:DNA Probes; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D008297:Male; D004676:Myelin Basic Protein; D009420:Nervous System / Q000187:drug effects*; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D014298:Trimethyltin Compounds / Q000633:toxicity*
D015342:DNA Probes; D004676:Myelin Basic Protein; D012333:RNA, Messenger; D014298:Trimethyltin Compounds; C046488:trimethyltin