Methylmercury-induced movement and postural disorders in developing rat: loss of somatostatin-immunoreactive interneurons in the striatum.
Tissue concentrations of the neuropeptide somatostatin and the specific activities of glutamic acid decarboxylase (GAD) were measured in several regions of the central nervous system in young rats, following chronic postnatal administration of methylmercuric chloride. By the beginning of the fourth postnatal week, these animals exhibited clinical signs of a mixed spastic/dyskinetic syndrome with visual deficits. At the onset of neurological impairment, a significant decrease in GAD activity was detected in the occipital cortex (48-49%) and striatum (45-50%) when compared to either normal or weight-matched controls. At one subclinical stage of toxicity, decreased GAD activity was detected only in the occipital cortex (29-30%). Tissue levels of somatostatin did not change significantly in the occipital cortex of methylmercury-treated animals at any stage of the experiment. However, somatostatin levels in the striatum were significantly reduced at the onset of neurological impairment (55-57%) and at one subclinical stage of toxicity (49-54%). Immunohistochemistry for somatostatin- and neuropeptide Y-immunoreactive neurons confirmed a marked loss of cells in the dorsolateral region of the striatum with atrophy of the surviving neurons. In the cerebral cortex of methylmercury-treated animals the morphology and distribution of somatostatin-positive neurons appeared normal. In view of the reported co-localization of GAD and somatostatin in some non-pyramidal neurons of the cerebral cortex, these results indicate that methylmercury-induced lesions of the developing cerebral cortex involve a subpopulation of GABAergic neurons which are not co-localized with somatostatin. In the striatum, where GAD and somatostatin are not co-localized within the same neurons, methylmercury-induced lesions involve both GABAergic and somatostatin-positive neurons.
D000375:Aging; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology; D003342:Corpus Striatum / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006651:Histocytochemistry; D007150:Immunohistochemistry; D007395:Interneurons / Q000378:metabolism*; D008297:Male; D008767:Methylmercury Compounds / Q000633:toxicity*; D009069:Movement Disorders / Q000139:chemically induced* / Q000378:metabolism; D009252:NADPH Dehydrogenase / Q000032:analysis; D009410:Nerve Degeneration / Q000187:drug effects; D009478:Neuropeptide Y / Q000378:metabolism; D011187:Posture; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000378:metabolism*
D008767:Methylmercury Compounds; D009478:Neuropeptide Y; D013004:Somatostatin; D009252:NADPH Dehydrogenase; D005968:Glutamate Decarboxylase; C004925:methylmercuric chloride