title: Molecular stress response in the CNS of mice after systemic exposure to interferon-alpha, ionizing radiation and ketamine.
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.
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. XRLowe@lbl.gov
authors.forename: Xiu R
authors.initials: XR
authors.lastname: Lowe
authors.forename: Francesco
authors.initials: F
authors.lastname: Marchetti
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Lu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wyrobek
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D005720:Gamma Rays / Q000009:adverse effects; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000633:toxicity*; D007649:Ketamine / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects*; D020107:Troponin T / Q000096:biosynthesis
chemical_list: D016898:Interferon-alpha; D020107:Troponin T; D007649:Ketamine