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Updated: Jun 26, 2026
A Mouse Model of Fatigue Induced by Peripheral Irradiation
Published on: March 17, 2017
Molecular stress response in the CNS of mice after systemic exposure to interferon-alpha, ionizing radiation and
Xiu R Lowe1, Francesco Marchetti, Xiaochen Lu
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.
Insights
Troponin T1 (Tnnt 1) expression in the brain
Area of Science:
- Neuroscience
- Molecular Biology
- Biomarkers
Background:
- Ketamine, an NMDA receptor antagonist, previously induced troponin T1 (Tnnt 1) expression in the mouse CNS.
- Tnnt 1 is hypothesized to be an early molecular biomarker for CNS stress response.
Purpose of the Study:
- To investigate the regional expression of Tnnt 1 in the mouse brain following exposure to interferon-alpha (IFN-alpha) and gamma radiation.
- To compare Tnnt 1 expression patterns across different CNS regions and treatment types.
Main Methods:
- Adult mice were systemically exposed to IFN-alpha or gamma radiation (10cGy or 2Gy).
- RNA in situ hybridization was used to analyze regional Tnnt 1 transcript expression.
- Expression patterns were compared with previous ketamine treatment data.
Main Results:
- Tnnt 1 expression was consistently induced in cerebral cortex and hippocampus pyramidal neurons across all treatments.
- Ionizing radiation and ketamine induced Tnnt 1 in cerebellar Purkinje cells, but IFN-alpha did not.
- Glial cells did not show induced Tnnt 1 expression with any treatment.
Conclusions:
- Induced Tnnt 1 expression in pyramidal neurons of the cortex and hippocampus suggests its role as an early biomarker of CNS stress.
- Tnnt 1's differential expression in Purkinje cells indicates region-specific responses to different stressors.
