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Supraphysiological levels of coticosterone and kainic acid: failure to find increased hippocampal neurotoxicity in the kainate resistant C57BL/6J mouse.
Benkovic-SA; Callaghan-JPO; Miller-DB
Toxicologist 2001 Mar; 60(1):372
Chronic stress mediated through glucocorticoids has been shown to exacerbate neurotoxicity in susceptible populations. To evaluate the role of glucocorticoids in the effects of chronic stress on neurotoxicity, as well as the role of strain in toxicant susceptibility, supraphysiological dosages of corticosterone (CORT)(200 mg/90d release pellet, s.c. implant) and its interactions with kainic acid (KA) neurotoxicity were examined in non-susceptible C57BI/6J mice. Dose-response comparisons between the KA susceptible strain FVB/N and C57BI/6J mice revealed a 25mg/kg (i.p.) dosage caused differential patterns of seizures in the two strains with FVB mice averaging 4 (Racine scale of 1 - 6) while C57 mice averaged 1. KA produced substantial CAI cell loss in FVB/N mice accompanied by elevations in the injury related marker of astrocytic hypertrophy, GFAP (673% over control, seven day survival), while C57BI/6J mice displayed no observable cell loss and only minor elevations in GFAP (44% over control, seven day survival). CORT exposure for four weeks prior to KA caused marked decreases in thymic and spleen, but not body weights. No overt cell loss was observed in CORT exposed mice, but GFAP was down-regulated in hippocampus as assessed by ELISA and diminished immunohisrochemical signal. CORT pretreatment did not alter the GFAP response observed after KA treatment, or produce identifiable hippocampal cell loss. Our data confirm that CORT down-regulates GFAP in mouse brain and that there are differences in the susceptibility of mouse strains to KA-induced hippocampal damage. These results suggest that stress will not increase the neurotoxic effects of KA, other excitotoxicants, or potentially, other hippocampal insults in the resistant C57B1/6J mouse. It is likely that individuals genetically susceptible to a given toxicant may be more prone to stress-induced exacerbation of toxicity.
Neurological-system; Neurological-diseases; Neurological-reactions; Neurotoxicity; Stress; Laboratory-animals
Issue of Publication
The Toxicologist. Society of Toxicology 40th Annual Meeting, March 25-29, 2001, San Francisco, California
Page last reviewed: March 11, 2019
Content source: National Institute for Occupational Safety and Health Education and Information Division