Suicide is one of the leading causes of death globally for all ages, and as such presents a very serious problem for clinicians worldwide. However, the underlying neurobiological pathology remains to a large extent unknown. In order to address this gap, we have carried out a genome-wide investigation of the gene expression in the amygdala, hippocampus, prefrontal cortex and thalamus in post-mortem brain samples obtained from 20 suicide completers and 7 control subjects. By KEGG enrichment analysis indicated we identified novel clusters of downregulated pathways involved in antigen neutralization and autoimmune thyroid disease (amygdala, thalamus), decreased axonal plasticity in the hippocampus. Two upregulated pathways were involved in neuronal death in the hippocampus and olfactory transduction in the thalamus and the prefrontal cortex. Autoimmune thyroid disease pathway was downregulated only in females. Metabolic pathways involved in Notch signaling amino acid metabolism and unsaturated lipid synthesis were thalamus-specific. Suicide-associated changes in the expression of several genes and pseudogenes that point to various functional mechanisms possibly implicated in the pathology of suicide. Two genes (SNORA13 and RNU4-2) involved in RNA processing were common to all brain regions analyzed. Most of the identified gene expression changes were related to region-specific dysregulated manifestation of genetic and epigenetic mechanisms underlying neurodevelopmental disorders (SNORD114-10, SUSd1), motivation, addiction and motor disorders (CHRNA6), long-term depression (RAB3B), stress response, major depression and schizophrenia (GFAP), signal transduction at the neurovascular unit (NEXN) and inhibitory neurotransmission in spatial learning, neural plasticity (CALB2; CLIC6, ENPP1). Some of the differentially expressed genes were brain specific non-coding RNAs involved in the regulation of translation (SNORA13). One, (PARM1) is a potential oncogene and prognostic biomarker for colorectal cancer with no known function in the brain. Disturbed gene expression involved in antigen neutralization, autoimmunity, neural plasticity, stress response, signal transduction at the neurovascular unit, dysregulated nuclear RNA processing and translation and epigenetic imprinting signatures is associated with suicide and point to regulatory non-coding RNAs as potential targets of new drugs development.
After cerebral ischemia, the ratio between astroglial cells and neurons in the neurovascular unit is disrupted in the perilesional area. We hypothesized that restoring the balance within the neurovascular unit may lead to an improved neurorestoration after focal ischemia. Recently, an innovative technology has been invented to efficiently convert proliferating astroglial cells into neurons in the injured young brain. However, the conversion efficacy of this technology has not been explored in the post-stroke brains of the aged rodents. To this end, we used a retroviral delivery system encoding the transcription factor Ngn2 alone or in combination with the antiapoptotic factor Bcl-2 to target proliferating astrocytes in the neocortex of young and aged mice after cerebral ischemia. Successful direct in vivo reprogramming of reactive glia into neuroblasts and mature neurons was assessed by cellular phenotyping. We found that the conversion efficacy of proliferating astrocytes into neurons after cerebral ischemia in young and aged mice is disappointingly low, most likely because the therapeutic vectors carrying the conversion gene are engulfed by phagocytes shortly after intracortical administration. We conclude that other viral vectors and combinations of transcription factors should be employed to improve the efficacy of glia-to-neuron conversion after stroke in young and aged rodents.
Let alone calorie restriction, life span extension in higher organisms has proven to be difficult to achieve using simple drugs. Previous studies have shown that the polyamine spermidine increased the maximum life span in C. elegans and the median life span in mice. However, younger subjects (< 40 years of age) are infrequently prescribed nor self-medicating with antiaging drugs. Therefore, in the present study, we aimed at assessing the effect of long-term treatment with spermidine given in the drinking water on behavioral performance and longevity of male, middle-aged Sprague-Dawley rats. We report that spermidine given in the drinking water did not extend neither the median nor the maximum life span of the middle-aged male Sprague-Dawley rats. However, spermidine treatment had a beneficial effect on the body weight and the kidney tubules, liver, and heart morphology. Behaviorally, spermidine led to a reduction in anxiety and an increase in curiosity, as assessed by exploratory behavior. Moreover, long-term treatment with spermidine enhanced autophagy in the brain and led to a diminished expression of the inflammatory markers, Tgfb, CD11b, Fcgr1, Stat1, CR3, and GFAP mRNAs in several cortical region and hippocampus of the treated rats suggesting that one beneficial effect of the long-term treatment with spermidine is an attenuated proinflammatory state in the aged brain. Our results suggest that long-term treatment with spermidine increases health span of middle-aged rats by attenuating neuroinflammation and improving anxiety and exploratory behavior.
The prevalance of depression and anxiety is higher at the patients diagnosticated with viral liver disease. The corelation between stress and chronic liver disease is a natural, implicit one, but still insufficiently studied. The study has the objective of finding out the clinical and also biochemical correlations between stress and chronic viral diseases. Our research was realised on a group of 78 patients with chronic viral liver disease, who underwent an evaluation of the stress level, both from a subjective point of view and based on concrete methods like questionnaires. The patients were asked to espress their state more or less affected by stress, and, subsequently, they were subjected to a questionnaire that was analyzed, followed by establishing the necessary correlations. Our patients were also evaluated by cardiologicaly, psychologicaly and psyhiatricaly examinations. After the first evaluation we had these results :38 patients (49.19%) consider that they have an average stress level, 18 patients (22.58%) have a high stress level. Only 22 patients (28.22%) declared stress was at a low level. We divided the pacients in two groups, function of Qt (questionare total score) results and we observed that a number of 38 patients ( 49.19%) registered �Qt 20 and 40 patients (50.81%) had Qt � 20, 63 patients (50.81%).We found a strong correlation between the patients� subjective evaluation of the stress level and the objective evaluation of stress level according to the used questionnaire, which confirms the objectivity of our study. We found a direct corelation, with a morphological, biochemical and functional support between stress and the arrhythmia risk in the evolution of chronic liver disease. We consider very important a complex examination psychiatricaly, psychologicaly and cardiological of the pacients diagnosticated with viral liver disease in order to help them and to prevent arrhythmic events, depression, anxiety and other mood disorders.
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