| Sequelae of parenteral domoic acid administration in rats: comparison of effects on different metabolic markers in brain. | |
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MedLine Citation:
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PMID: 9134959 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Parenterally administered domoic acid, a structural analog of the excitatory amino acids glutamic acid and kainic acid, has specific effects on brain histology in rats, as measured using different anatomic markers. Domoic acid-induced convulsions affects limbic structures such as hippocampus and entorhinal cortex, and different anatomic markers can detect these neurotoxic effects to varying degrees. Here we report effects of domoic acid administration on quantitative indicators of brain metabolism and gliosis. Domoic acid, 2.25 mg/kg i.p., caused stereotyped behavior and convulsions in approximately 60% of rats which received it. Six to eight days after domoic acid or vehicle administration, the animals were processed to measure regional brain incorporation of the long-chain fatty acids [1-(14)C]arachidonic acid ([14C]AA) and [9,10-(3)H]palmitic acid ([3H]PA), or regional cerebral glucose utilization (rCMRglc) using 2-[1-(14)C]deoxy-D-glucose, by quantitative autoradiography. Others rats were processed to measure brain glial fibrillary acidic protein (GFAP) by enzyme-linked immunosorbent assay. Domoic acid increased GFAP in the anterior portion of cerebral cortex, the caudate putamen and thalamus compared with vehicle. However, in rats that convulsed after domoic acid GFAP was significantly increased throughout the cerebral cortex, as well as in the hippocampus, septum, caudate putamen, and thalamus. Domoic acid, in the absence of convulsions, decreased relative [14C]AA incorporation in the claustrum and pyramidal cell layer of the hippocampus compared with vehicle-injected controls. In the presence of convulsions, relative [14C]AA incorporation was decreased in hippocampus regions CA1 and CA2. Uptake of [3H]PA into brain was unaffected. Relative rCMRglc decreased in entorhinal cortex following domoic acid administration with or without convulsions. These results suggest that acute domoic acid exposure affects discrete brain circuits by inducing convulsions, and that domoic acid-induced convulsions cause chronic effects on brain function that are reflected in altered fatty acid metabolism and gliosis. |
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Authors:
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N M Appel; S I Rapoport; J P O'Callaghan; J M Bell; L M Freed |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Brain research Volume: 754 ISSN: 0006-8993 ISO Abbreviation: Brain Res. Publication Date: 1997 Apr |
Date Detail:
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Created Date: 1997-07-15 Completed Date: 1997-07-15 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0045503 Medline TA: Brain Res Country: NETHERLANDS |
Other Details:
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Languages: eng Pagination: 55-64 Citation Subset: IM |
Affiliation:
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Division of Applied Pharmacology Research, Center for Drug Evaluation and Research, Food and Drug Administration, Laurel, MD 20708-2476, USA. appeln@cder.fda.gov |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arachidonic Acid / metabolism Autoradiography Biological Markers Brain / drug effects*, metabolism, pathology Carbon Radioisotopes Deoxyglucose / metabolism Glial Fibrillary Acidic Protein / metabolism Glucose / metabolism Infusions, Parenteral Kainic Acid / administration & dosage, analogs & derivatives*, toxicity Male Neurotoxins / administration & dosage, toxicity* Organ Specificity Palmitic Acid / metabolism Rats Rats, Inbred F344 Seizures / chemically induced, pathology Tritium |
| Chemical | |
Reg. No./Substance:
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0/Biological Markers; 0/Carbon Radioisotopes; 0/Glial Fibrillary Acidic Protein; 0/Neurotoxins; 10028-17-8/Tritium; 14277-97-5/domoic acid; 154-17-6/Deoxyglucose; 487-79-6/Kainic Acid; 50-99-7/Glucose; 506-32-1/Arachidonic Acid; 57-10-3/Palmitic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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