Methylmercury-induced movement and postural disorders in developing rat: high-affinity uptake of choline, glutamate, and gamma-aminobutyric acid in the cerebral cortex and caudate-putamen.
Subcutaneous administration of methylmercuric chloride to neonatal rats resulted in movement and postural disorders during the fourth postnatal week. Sodium-dependent high-affinity uptake of radiolabeled choline, glutamate, and gamma-aminobutyric acid (GABA) was measured in homogenates of cerebral cortex and caudate-putamen. There was a significant decrease in the uptake of [3H]choline in the cerebral cortex, but not in the caudate-putamen, at the onset of neurological impairment (73-75%) and at one subclinical stage of toxicity (58-64%). No significant differences in [3H]glutamate uptake were detected in either region. The uptake of [3H]GABA in the presence of 1 mM beta-alanine, which was employed to inhibit the glial uptake process, was reduced significantly in both the cerebral cortex and caudate-putamen at the onset of neurological impairment (50-62%) and at one subclinical stage (40-51%). This decrease in [3H]GABA uptake is consistent with the results of previous studies using this animal model, which demonstrated a preferential degeneration of GABAergic neurons in the cerebral cortex and caudate-putamen of methylmercury-treated animals. Because the high-affinity uptake of choline is the rate-limiting step for acetylcholine synthesis by cholinergic neurons, the decrease in [3H]choline uptake may reflect an abnormal development of cholinergic innervation of the cerebral cortex.
O'Kusky
J R
JR
Department of Pathology, University of British Columbia, Vancouver, Canada.
McGeer
E G
EG
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002794:Choline / Q000378:metabolism*; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D007700:Kinetics; D008767:Methylmercury Compounds / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects*; D009498:Neurotoxins / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D011187:Posture; D011699:Putamen / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005971:Glutamates; D008767:Methylmercury Compounds; D009498:Neurotoxins; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D002794:Choline; C004925:methylmercuric chloride