• Journal of Life Science
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• v.29 no.9
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• pp.1002-1009
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• 2019

Early life stress (ELS) increases the risk of depression. ELS may be involved in the susceptibility to subsequent stress exposure during adulthood. We investigated whether epigenetic mechanisms of p11 promoter affect the vulnerability to chronic unpredictable stress (CUS) induced by the maternal separation (MS). Mice pups were separated from their dams (3 hr/day from P1-P21). When the pups reached adulthood, we applied CUS (daily for 3 weeks). The levels of hippocampal p11 expression were analyzed by quantitative real-time PCR. The levels of acetylated and methylated histone H3 at p11 promoter were measured by chromatin immunoprecipitation. Depression-like behavior was measured by the forced swimming test (FST). The MS and CUS group exhibited significant decreases in p11 mRNA level and the MS plus CUS group had a greater reduction in this level than the CUS group. The MS plus CUS group also resulted in greater reduction in H3 acetylation than the CUS group. This reduction was associated with an upregulation of histone deacetylase 5. Additionally, the MS plus CUS group showed a greater decrease in H3K4met3 level and a greater increase in H3K27 met3 level than the CUS group. Consistent with the reduction of p11 expression, the MS plus CUS group displayed longer immobility times in the FST compared to the control group. Mice exposed to MS followed by CUS had much greater epigenetic alterations in the hippocampus compared to adult mice that only experienced CUS. ELS can exacerbate the effect of stress exposure during adulthood through histone modification of p11 gene.

• Development and Reproduction
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• v.12 no.2
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• pp.117-124
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• 2008

The efficient strategies to cope with unpredictable and/or harmful environmental changes have been developed by every organism in order to ensure its survival and continuity of it's own species. As a results, all living things on earth maintain dynamically internal stability via a process termed 'homeostasis' among physiological parameters despite of external environment changes. Stress is an emotional and physical response to threat homeostasis. Stress may have not only transient but rather permanent effect on the organism; recent evidence clearly show that prenatal stress could organize or imprint permanently physiological systems without any change in genetic codes, a process known as 'epigenetic programming'. In this review, a series of reproduction-associated events occurred in prenatally stressed male rats such as alteration in the structure of sexually dimorphic brain regions, modification of neurotransmitter metabolism, changes in reproductive endocrine status, and finally, disorders of sexual behavior will be introduced. The fetal brain is highly sensitive to prenatal programming and glucocorticoids in particular have powerful brain-programming properties. The chronic hyperactivation of fetal brain by maternal stress-induced glucocorticoid input will provide new program via increasing the neuroplasticities. This 'increased neuroplasticities' will be the basis for the 'increased phenotypic plasticities' rendering the organism's better adaptation to environmental challenges. In conclusion, organism who experienced 'harsh' environment in his fetal life seems to give up a certain portion of reproductive competence to make good chance of survival in his future life by epigenetic (re)programming.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.5
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• pp.371-376
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• 2014

Amino-acid neurotransmitter system dysfunction plays a major role in the pathophysiology of depression. Several studies have demonstrated the potential of amino acids as a source of neuro-specific biomarkers could be used in future diagnosis of depression. Only partial amino acids such as glycine and asparagine were determined from certain parts of rats' brain included hippocampi and cerebral cortex in previous studies. However, according to systematic biology, amino acids in different area of brain are interacted and interrelated. Hence, the determination of 34 amino acids through entire rats' brain was conducted in this study in order to demonstrate more possibilities for biomarkers of depression by discovering other potential amino acids in more areas of rats' brain. As a result, 4 amino acids (L-aspartic acid, L-glutamine, taurine and ${\gamma}$-amino-n-butyric acid) among 34 were typically identified as potentially primary biomarkers of depression by data statistics. Meanwhile, an antidepressant called Fluoxetine was employed to verify other potential amino acids which were not identified by data statistics. Eventually, we found L-${\alpha}$-amino-adipic acid could also become a new potentially secondary biomarker of depression after drug validation. In conclusion, we suggested that L-aspartic acid, L-glutamine, taurine, ${\gamma}$-amino-n-butyric acid and L-${\alpha}$-amino-adipic acid might become potential biomarkers for future diagnosis of depression and development of antidepressant.