Title:Characterization of the Early CNS Stress Biomarkers and Profiles Associated with Neuropsychiatric Diseases
Volume: 13
Issue: 6
Author(s): X. R. Lowe and A. J. Wyrobek
Affiliation:
Keywords:
Early CNS stress biomarker, Interferon, Radiation, Low-dose, Ketamine, Microarray, Neuropsychiatric diseases,
RNA in situ hybridization, Tnnt1, cerebral cortex, Alzheimer’s disease
Abstract: 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-α) 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.
