Characterization of the Early CNS Stress Biomarkers and Profiles Associated with Neuropsychiatric Diseases

R. Lowe, X.; J. Wyrobek, A.

doi:10.2174/138920212802510448

Title: Characterization of the Early CNS Stress Biomarkers and Profiles Associated with Neuropsychiatric Diseases

Journal Article · Tue Aug 07 00:00:00 EDT 2012 · Current Genomics

DOI:https://doi.org/10.2174/138920212802510448· OSTI ID:1629067

R. Lowe, X. ^[1]; J. Wyrobek, A. ^[2]

Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division; Kaiser Permanente Medical Center, Hayward, CA (United States). Dept. of Psychiatry
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division

Neuropsychiatric disorders (including dementia) have high personal, family, and social costs. Although many neuropsychiatric disorders share common patterns of symptoms and treatments, there are no validated biomarkers that define the underlying molecular mechanisms in the central nervous system (CNS). We hypothesize that there are early and common molecular changes in the CNS that will serve as sensitive indicators of CNS molecular stress and that will be predictive of neuropathological changes resulted in increasing the risk for neuropsychiatric diseases. Using the rodent model, we showed that systemic exposure to three diverse CNS stressors with different mechanisms of action (ketamine, low-dose and high-dose ionizing radiation, interferon-) induced the expression of troponin T1 (Tnnt 1) within hours in adult mouse brain tissue. Tnnt 1 expression was induced in neuronal (not glial) cells, the hippocampal zone of neurogenesis, cerebral cortex, amygdale, and choroid plexus, which are important CNS locations in behavior and mental health. We also identified nine neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue for hours after low-dose irradiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer’s disease. Our studies provide new molecular information on shared mechanisms and expression profiles of diverse neuropsychiatric disorders. This knowledge will be fundamental for developing molecular signatures of early CNS stress biomarker for early diagnosis and treatment of neuropsychiatric diseases.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1629067

Journal Information:: Current Genomics, Vol. 13, Issue 6; ISSN 1389-2029

Publisher:: Bentham Science PublishersCopyright Statement

Country of Publication:: United States

Language:: English

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Low-dose or low-dose-rate ionizing radiation–induced bioeffects in animal models Tang, Feng Ru; Loke, Weng Keong; Khoo, Boo Cheong Journal of Radiation Research, Vol. 58, Issue 2 https://doi.org/10.1093/jrr/rrw120	journal	December 2016
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59 BASIC BIOLOGICAL SCIENCES
Early CNS stress biomarker
Interferon
Radiation
Low-dose
Ketamine
Microarray
Neuropsychiatric diseases
RNA in situ hybridization
Tnnt1
Cerebral cortex
Alzheimer's disease

Title: Characterization of the Early CNS Stress Biomarkers and Profiles Associated with Neuropsychiatric Diseases

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