Myelin basic protein-messenger RNA (MBP-mRNA) expression during triethyltin-induced myelin edema.
Triethyltin (TET) is a neurotoxicant that produces severe but transient cerebral edema, characterized ultrastructurally by vacuolation of the intraperiod line of central nervous system (CNS) myelin. TET has been reported to depress levels of myelin basic protein (MBP), a protein thought to play a critical role in myelin compaction. In the present study, the genomic expression (i.e., mRNA) of MBP was monitored throughout the pathogenesis of TET-induced myelin edema and recovery in Sprague-Dawley rats given a single injection of a neuropathic (8.0 mg/kg) or non-neuropathic (0.8 mg/kg) dose of TET-bromide. Levels of MBP-mRNA from the anterior and posterior brain were collected 1 hr, 3 hr, 2d, and 7d, postexposure. The optic nerve and caudal brainstem, representing anterior and posterior brain sites, respectively, were examined at the same time-points for ultrastructural evidence of edema and recovery. Our data indicate that neuropathic doses (8.0 mg/kg) of TET significantly stimulated MBP transcript throughout the brain at all exposure time-points. The magnitude and time-course of this stimulation differed in the anterior and posterior brain, with the latter region showing higher levels of MBP-mRNA. In the posterior brain, the highest levels of mRNA correlated with the appearance of edema in the caudal brainstem. In the anterior brain, MBP-mRNA levels were only marginally increased over controls. Ultrastructural evidence of myelin edema was confined to the brainstem in rats treated with neuropathic dose of TET. Intralamellar vacuolation appeared at 3 hr and 2d postexposure and could be correlated with peak levels of MBP transcript, whereas, recompacted myelin, which appeared by 7d postexposure, was associated with declining levels of the mRNA. Ultrastructural changes in the oligodendroglia were suggestive of metabolic stimulation and correlated with high MBP-mRNA levels. In summary, these data indicate that an initial genomic event in TET-induced myelin edema is stimulation of MBP transcript.
Veronesi
B
B
U.S. Environmental Protection Agency, Health Effects Research Laboratory, RTP, North Carolina 27711.
Jones
K
K
Gupta
S
S
Pringle
J
J
Mezei
C
C
D000818:Animals; D015152:Blotting, Northern; D002493:Central Nervous System Diseases / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics; D015342:DNA Probes; D004487:Edema / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D008297:Male; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism*; D009186:Myelin Sheath; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D014267:Triethyltin Compounds / Q000633:toxicity*
D015342:DNA Probes; D004676:Myelin Basic Protein; D012333:RNA, Messenger; D014267:Triethyltin Compounds; D004247:DNA