Correlation of Expression Changes between Genes Controlling 5-HT Synthesis and Genes Crh and Trh in the Midbrain Raphe Nuclei of Chronically Aggressive and Defeated Male Mice

Midbrain raphe nuclei (MRNs) contain a large number of serotonergic neurons associated with the regulation of numerous types of psychoemotional states and physiological processes. The aim of this work was to study alterations of the MRN transcriptome in mice with prolonged positive or negative fighting experience and to identify key gene networks associated with the regulation of serotonergic system functioning. Numerous genes underwent alterations of transcription in the MRNs of male mice that either manifested aggression or experienced social defeat in daily agonistic interactions. The expression of the Tph2 gene encoding the rate-limiting enzyme of the serotonin synthesis pathway correlated with the expression of many genes, 31 of which were common between aggressive and defeated mice and were downregulated in the MRNs of mice of both experimental groups. Among these common differentially expressed genes (DEGs), there were genes associated with behavior, learning, memory, and synaptic signaling. These results suggested that, in the MRNs of the mice, the transcriptome changes associated with serotonergic regulation of various processes are similar between the two groups (aggressive and defeated). In the MRNs, more DEGs correlating with Tph2 expression were found in defeated mice than in the winners, which is probably a consequence of deeper Tph2 downregulation in the losers. It was shown for the first time that, in both groups of experimental mice, the changes in the transcription of genes controlling the synthesis and transport of serotonin directly correlate with the expression of genes Crh and Trh, which control the synthesis of corticotrophin- and thyrotropin-releasing hormones. Our findings indicate that CRH and TRH locally produced in MRNs are related to serotonergic regulation of brain processes during a chronic social conflict.

Study on the Relationship Between Musculoskeletal Disorders, BDNF Gene, TPH-2 Gene, and Mental Health in Coal Mine Workers in China

Background: Coal is the core energy source of the global energy system. To ensure the sustainable development of the coal industry, the mental health of coal miners is crucial. Methods: This cross-sectional study was conducted between August 2018 and June 2019. A total of 1,675 coal miners were surveyed using the Musculoskeletal Disorders (MSDs) Questionnaire and the Symptom Checklist-90 (SCL-90). At the same time, polymorphisms in the BDNF gene (rs6265, rs10835210) and TPH2 gene (rs4570625, rs4131347) in whole blood DNA were detected to analyze the influence of a gene-environment interaction on mental health. Results: The results showed that the mental health status of coal miners was poorer than the Chinese norm (P < 0.05). The mental health status of workers with MSDs was lower; MSDs interact with the BDNF gene rs6265 and TPH2 gene rs4570625, which affects mental health. Conclusions: It is suggested that employers should improve the working environment of workers, shorten the working time, pay attention to the mental health of workers, and provide timely psychological counseling to workers who suffer from mental health problems, so as to improve workers’ mental health and working ability, as well as their quality of life.

Genetic Features of Dynamics of Heart Rate Variability at Work with Perspective Human — Computers Interfaces

The aim of the work was to assess the parameters of the heart rate variability of the user by the interfaces of the brain-computer, oculographic, respiratory, myographic, depending on the SNV in the genes that are somehow related to the functioning of the autonomic nervous system. Heart rate variability is an indicator of the cardiovascular system and a number of mechanisms regulating the whole organism, which can be used as one of the markers of the state of a human operator. The paper analyzes the association of point mutations of the HTR2A, APOE and TPH2 genes with HRV indices when users master a number of human-computer interfaces: brain-computer, oculographic, myographic and respiratory. The brain-computer interface is implemented on stable (well-established) visual evoked potentials; oculographic interface provided a set of text by eye movement, myographic provided the same task as the two above interfaces, due to changes in the user’s muscular activity; respiratory interface — due to changes in breathing. It has been shown that the SNV of the HTR2A and TPH2 genes involved in serotonin metabolism are associated with HRV indices in the development of neurocomputer interfaces. The SNV rs6313 HTR2A C allele carriers are characterized by higher rates of tonic effects on HRV when working with the oculographic interface, which is probably associated with an increase in serotonin receptor expression, which is involved in the vegetative regulation of heart rhythm. The genotype T / T SNV rs4290270 of the TPH2 gene is associated with a large spread of cardiointervals. This is probably due to an increase in the expression of the TPH2 gene, which catalyzes the limiting step of serotonin synthesis.

Vitamin D moderates the interaction between 5-HTTLPR and childhood abuse in depressive disorders

A complex interplay between genetic and environmental factors determines the individual risk of depressive disorders. Vitamin D has been shown to stimulate the expression of the tryptophan hydroxylase 2 (TPH2) gene, which is the rate-limiting enzyme for serotonin production in the brain. Therefore, we investigate the hypothesis that serum vitamin D levels moderate the interaction between the serotonin transporter promotor gene polymorphism (5-HTTLPR) and childhood abuse in depressive disorders. Two independent samples from the Study of Health in Pomerania (SHIP-LEGEND: n = 1 997; SHIP-TREND-0: n = 2 939) were used. Depressive disorders were assessed using questionnaires (BDI-II, PHQ-9) and interview procedures (DSM-IV). Besides serum vitamin D levels (25(OH)D), a functional polymorphism (rs4588) of the vitamin D-binding protein is used as a proxy for 25(OH)D. S-allele carriers with childhood abuse and low 25(OH)D levels have a higher mean BDI-II score (13.25) than those with a higher 25(OH)D level (9.56), which was not observed in abused LL-carriers. This significant three-way interaction was replicated in individuals with lifetime major depressive disorders when using the rs4588 instead of 25(OH)D (p = 0.0076 in the combined sample). We conclude that vitamin D relevantly moderates the interaction between childhood abuse and the serotonergic system, thereby impacting vulnerability to depressive disorders.

The Role of Dorsal Raphe Serotonin Neurons in the Balance between Reward and Aversion

Background: Reward processing is fundamental for animals to survive and reproduce. Many studies have shown the importance of dorsal raphe nucleus (DRN) serotonin (5-HT) neurons in this process, but the strongly correlative link between the activity of DRN 5-HT neurons and rewarding/aversive potency is under debate. Our primary objective was to reveal this link using two different strategies to transduce DRN 5-HT neurons. Methods: For transduction of 5-HT neurons in wildtype mice, adeno-associated virus (AAV) bearing the mouse tryptophan hydroxylase 2 (TPH2) gene promoter was used. For transduction in Tph2-tTA transgenic mice, AAVs bearing the tTA-dependent TetO enhancer were used. To manipulate the activity of 5-HT neurons, optogenetic actuators (CheRiff, eArchT) were expressed by AAVs. For measurement of rewarding/aversive potency, we performed a nose-poke self-stimulation test and conditioned place preference (CPP) test. Results: We found that stimulation of DRN 5-HT neurons and their projections to the ventral tegmental area (VTA) increased the number of nose-pokes in self-stimulation test and CPP scores in both targeting methods. Concomitantly, CPP scores were decreased by inhibition of DRN 5-HT neurons and their projections to VTA. Conclusion: Our findings indicate that the activity of DRN 5-HT neurons projecting to the VTA is a key modulator of balance between reward and aversion.