Genomic instability in the brain: Etiology, pathogenesis and new biological markers of psychiatric disorders
The latest advances in molecular medicine, medical genetics and neurobiology have provided for a new look at processes occurring in cells of the brain and have allowed to discover previously unknown phenomena associated with mental traits and to propose new biomedical direction which include genomics, psychiatry and neurobiology - brain genomics. The application of modern molecular and cellular technologies of genome analysis in the brain in common psychiatric disorders (autism, schizophrenia and Alzheimer's disease) has shown that genomic instability is a phathogenetic mechanism of central nervous system abnormalities and plays a role in the brain development. Genomic disbalance alters neural homeostasis leads to cell death and is an important biological marker of psychiatric disorders which determine genomic pathways. These alterations lead to synaptic disfunction and neurodegeneration. In the present review, the main advances of brain genomics and potential application in diagnostic, clinical and therapeutic practice.
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ABSTRACT: To investigate the effects of maternal lead (Pb) exposure on the learning and memory ability and expression of interleukin1-β (IL1-β), tumor necrosis factor (TNF-α) and beta amyloid protein (Aβ) in cerebral cortex of mice offspring. Pb exposure initiated from beginning of gestation to weaning. Pb acetate administered in drinking solutions was dissolved in distilled deionized water at the concentrations of 0.1%, 0.5% and 1% groups, respectively. On the PND21, the learning and memory ability were tested by water maze test and the Pb levels were also determined by graphite furnace atomic absorption spectrometry. The expression of IL1-β, TNF-α and Aβ in cerebral cortex was measured by immunohistochemistry and western blotting. The Pb levels in blood and cerebral cortex of all exposure groups were significantly higher than that of the control group (P<0.05). In water maze test, the performances of 0.5% and 1% groups were worse than that of the control group (P<0.05). The expression of IL1-β, TNF-α and Aβ was increased in Pb exposed groups than that of the control group (P<0.05). The high expression of IL1-β, TNF-α and Aβ in the cerebral cortex of pups may contribute to the impairment of learning and memory associated with maternal Pb exposure.
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