Cell specific enzyme markers as indicators of neurotoxicity: effects of acute exposure to methylmercury.
In order to assess the sensitivity of several cell specific enzyme markers (tyrosine hydroxylase (TH), glutamic acid decarboxylase, choline acetyltransferase, glutamine synthetase (GS), neuron specific and non-neuronal enolase and 2',3'-cyclic nucleotide phosphohydrolase (CNP] as indices of neurotoxicity, changes in their activities were monitored after rats were treated with two doses of the neurotoxic agent, methylmercury chloride (MMC). Comparisons were also made of any histopathological changes occurring in the tissues examined. At the low dose rate (3.36 mg Hg/kg, po, for 14 days), the rats exhibited less body weight gain compared to untreated animals. No change in either the neuronal or noneuronal enzyme markers was observed in brain but a significant increase in the myelin marker, CNP, and total enolase activity was seen in the optic nerve. Morphological evaluation by light microscopy indicated no discernible neuronal lesions in MMC-exposed animals. At the higher MMC dose (7.05 mg Hg/kg, po, for 7 days), there was about a 20% loss in the body weight of treated animals and partial hind limb paralysis was observed. Of all the neuronal marker enzymes examined, only TH was found to be decreased in the striatum. The proliferating astroglial marker, GS, was elevated only in the cerebellum. CNP was found to be decreased in both the optic and sciatic nerve. As in the lower dose group no pathological changes were observed at the light microscopic level in the brain of MMC-treated rats. These data suggest that of the cell specific marker enzymes studied, GS in the cerebellum and TH in the striatum may be useful biochemical markers for the neurotoxic action of MMC.
Kung
M P
MP
Department of Pharmacology, State University of New York, School of Medicine, Buffalo 14214.
Kostyniak
P J
PJ
Olson
J R
JR
Sansone
F M
FM
Nickerson
P A
PA
Malone
M A
MA
Ziembiec
N
N
Roth
J A
JA
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000032:analysis; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D002795:Choline O-Acetyltransferase / Q000032:analysis; D004798:Enzymes / Q000032:analysis*; D005968:Glutamate Decarboxylase / Q000032:analysis; D005974:Glutamate-Ammonia Ligase / Q000032:analysis; D008297:Male; D008767:Methylmercury Compounds / Q000633:toxicity; D009420:Nervous System / Q000187:drug effects*; D010751:Phosphopyruvate Hydratase / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D015415:Biomarkers; D004798:Enzymes; D008767:Methylmercury Compounds; D014446:Tyrosine 3-Monooxygenase; D002795:Choline O-Acetyltransferase; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D005968:Glutamate Decarboxylase; D010751:Phosphopyruvate Hydratase; D005974:Glutamate-Ammonia Ligase; C004925:methylmercuric chloride