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Neurotoxicology. 2009 Mar;30(2):261-8. doi: 10.1016/j.neuro.2008.12.012. Epub 2008 Dec 31.

Molecular stress response in the CNS of mice after systemic exposure to interferon-alpha, ionizing radiation and ketamine.

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  • 1Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. XRLowe@lbl.gov

Abstract

We previously showed that the expression of troponin T1 (Tnnt 1) was induced in the central nervous system (CNS) of adult mice 30min after treatment with ketamine, a glutamate N-methyl-D-aspartic acid (NMDA) receptor antagonist. We hypothesized that Tnnt 1 expression may be an early molecular biomarker of stress response in the CNS of mice. To further evaluate this hypothesis, we investigated the regional expression of Tnnt 1 in the mouse brain using RNA in situ hybridization 4h after systemic exposure to interferon-alpha (IFN-alpha) and gamma ionizing radiation, both of which have be associated with wide ranges of neuropsychiatric complications. Adult B6C3F1 male mice were treated with either human IFN-alpha (a single i.p. injection at 1 x 10(5)IU/kg) or whole body gamma-radiation (10cGy or 2Gy). Patterns of Tnnt 1 transcript expression were compared in various CNS regions after IFN-alpha, radiation and ketamine treatments (previous study). Tnnt 1 expression was consistently induced in pyramidal neurons of cerebral cortex and hippocampus after all treatment regimens including 10cGy of ionizing radiation. Regional expression of Tnnt 1 was induced in Purkinje cells of cerebellum after ionizing radiation and ketamine treatment; but not after IFN-alpha treatment. None of the three treatments induced Tnnt 1 expression in glial cells. The patterns of Tnnt 1 expression in pyramidal neurons of cerebral cortex and hippocampus, which are both known to play important roles in cognitive function, memory and emotion, suggest that the expression of Tnnt 1 may be an early molecular biomarker of induced CNS stress.

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