Moderate concentration of Lactobacillus metabolites does not adversely affect mouse sperm.

Many couples in contemporary societies suffer from infertility of unexplained origins (idiopathic). A promising treatment strategy within this context involves the administration to women of preparations containing lactic acid bacteria (Lactobacillus) and/or their metabolites. Recent investigations underscore the role of lactobacilli in sustaining female fertility and enhancing the effectiveness of assisted reproductive techniques. There have also been reports describing the effect of lactobacilli on sperm functions, but our knowledge in this domain remains uncertain. In this study, the effect of supernatant from Lactobacillus rhamnosus culture on mouse sperm viability and motility was tested. The protective properties of lactobacilli metabolites against hydrogen peroxide-induced DNA damage were also verified. It was shown that the metabolites have no effect on viability, motility, and genome integrity of spermatozoa, but in excessive concentrations they become toxic. The obtained results imply that probiotic and/or postbiotic preparations taken by women should not adversely affect the sperm of their partners, provided the dose is correctly selected.

Long-run real-time PCR analysis of repetitive nuclear elements as a novel tool for DNA damage quantification in single cells: an approach validated on mouse oocytes and fibroblasts.

Since DNA damage is of great importance in various biological processes, its rate is frequently assessed both in research studies and in medical diagnostics. The most precise methods of quantifying DNA damage are based on real-time PCR. However, in the conventional version, they require a large amount of genetic material and therefore their usefulness is limited to multicellular samples. Here, we present a novel approach to long-run real-time PCR-based DNA-damage quantification (L1-LORD-Q), which consists in amplification of long interspersed nuclear elements (L1) and allows for analysis of single-cell genomes. The L1-LORD-Q was compared with alternative methods of measuring DNA breaks (Bioanalyzer system, γ-H2AX foci staining), which confirmed its accuracy. Furthermore, it was demonstrated that the L1-LORD-Q is sensitive enough to distinguish between different levels of UV-induced DNA damage. The method was validated on mouse oocytes and fibroblasts, but the general idea is universal and can be applied to various types of cells and species.

Self-Assessment of Physical Fitness and Health versus Motivational Value of Physical Activity Goals in People Practicing Fitness, Football, Martial Arts and Wheelchair Rugby.

The aim of the study was to determine the relationship between self-assessment of physical fitness and health, and the motivational role of physical activity goals in people, depending on their sports discipline. The study included 470 men and 218 women, aged 18-45, from western and southern Poland. The respondents practiced sports recreationally (fitness-F), competitively (football-FB, martial arts-MA), and for rehabilitation and sports purposes (wheelchair rugby-R). The standardized questionnaire for the motivational role of physical activity goals (Inventory of Physical Activity Objectives, IPAO) by Lipowski and Zaleski and the authors' questionnaire on lifestyle were used. In the statistical analyses, non-parametric statistics were used. Individuals with very high and high self-assessment of their physical fitness and very good self-assessment of health achieved higher scores on the motivational value scale, time management, motivational conflict and multidimensionality of physical activity goals (p < 0.05). Respondents who assessed their health as very good achieved lower results on the perseverance scale, compared to those who assessed their health as good or poor. Self-assessment of physical fitness had a positive, high and moderate correlation with the self-assessment of health in people practicing wheelchair rugby, fitness, football and martial arts (r = 0.61; r = 0.52; r = 0.41; r = 0.40, respectively). Correlations were found between the motivational role and time management in people practicing fitness (r = 0.81), football (r = 0.66) and martial arts (r = 0.45), and multidimensionality of goals in those practicing fitness (r = 0.65) and martial arts (r = 0.42) Wheelchair rugby players scored the highest on all KCAF scales (except for motivational conflict). Self-assessment of physical fitness of wheelchair rugby players and fitness practitioners was negatively correlated with time management (r = -0.68; r = -0.49), multidimensionality of goals (r = -0.51; r = -0.49) and motivational values (r = -0.43; r = -0.43). The demonstrated relationships indicated that there was a need to strengthen the self-esteem and motivation for physical activity, promoting perseverance, the ability to focus on the implementation of one's goals and prioritizing the goals among people practicing various sports disciplines.

The Intensity of the Health Behaviors of People Who Practice Wheelchair Basketball, Wheelchair Rugby and Para-Rowing.

Sports serve people with disabilities as a form of rehabilitation. Sporting activity is a health-promoting behavior choice and a chance to achieve the best possible sports results. The aim of this study was to evaluate the intensity of health behaviors in people practicing wheelchair basketball, wheelchair rugby and para-rowing. The study encompassed 176 athletes with disabilities, aged 19 to 49 (mean age 34.41 ± 8.56), from all over Poland. Men accounted for 83.5% of the respondents. They all had a significant degree of disability and used wheelchairs in their daily lives. The authors used Juczynski's Health Behavior Inventory (HBI) and the authors' own survey questionnaire. Nonparametric tests were used. A greater intensity of health behaviors in general (HBI­point score) and in four categories (correct eating habits­CEH, preventive behaviors­PB, positive mental attitude­PMA, health practices­HP) was observed in rugby and basketball players (compared with para-rowers). Disabled rowers achieved the poorest results. Polish Champions scored better results in preventive behaviors (PB) and weaker results in positive mental attitude (PMA)compared with those practicing amateur sport. Respondents who trained every day and had the longest weekly exercise time (>360 min) achieved the highest results in HBI in general and in all categories compared with those who trained once a week for less than 120 min a week. Respondents with higher education, those in a better financial situation, those who were employed and married, and those who were rural residents displayed a greater intensity of health-related behaviors. People in a more difficult financial situation, who had less education, who were cohabiting, and who lived on only a pension presented more preventive behaviors. There is a need for systemic health education aimed at people with disabilities who practice various sports disciplines.

Deletion in the Y chromosome of B10.BR-Ydel mice alters transcription from MSYq genes and has moderate effect on DNA methylation.

B10.BR-Ydel male mice with large deletion in the male-specific region of the Y chromosome long arm (MSYq) are very useful experimental model which requires, however, more detailed characterization. In the present study, the influence of the deletion on transcript levels of MSYq genes (Ssty1, Ssty2, Sly, Srsy, Asty, Orly) and homologous to them X-linked genes (Sstx, Slx, Slxl1, Srsx) was assessed. Quantitative PCR analysis showed that in testes of B10.BR-Ydel males activity of Ssty1 is unchanged, but transcription from all other MSYq genes is highly reduced and reaches from 59 % to only 5 % of the control levels. The decrease in expression of MSYq genes is accompanied by the two-fold increase in expression of Slx and Slxl1 genes. This is the first functional characterization of the deletion in B10.BR-Ydel strain. Another aim of the study was to reveal the mechanism through which deleted Y chromosome of B10.BR-Ydel males could alter phenotype of their female progeny, what was documented in our previous works. Epigenetic inheritance hypothesis was tested by microarray analysis of DNA methylation in B10.BR-Ydel and control B10.BR sperm. The assessment revealed moderate differences and allowed concluding that the mutated Y chromosome can influence traits of females from the next generation partially through altering sperm DNA methylation, but probably some additional mechanisms are engaged here. Breeding data indicate that feminization of pre- and neonatal environment in which next generation females develop is one of such additional mechanisms.

Physical Activity and the Quality of Life of Female Students of Universities in Poland.

Physical activity increases human health potential and has an impact on achieving a higher quality of life in society. The aim of our research was to determine the relationship between a physically active lifestyle and the quality of life of female students in the context of demographic and social factors (major, age, marital status, professional activity). The research was conducted among a group of 285 women studying physical culture and social sciences in Poznan and Szczecin (Poland). Average age: 22.7 ± 4.90. The standardized World Health Organization Quality of Life-BREF (WHQOL-BREF) questionnaire was used to assess the quality of life of female students, and the original survey technique was used to study the lifestyle of people undertaking physical activity in the context of socio-demographic factors. Nonparametric statistics were applied in the analyses of the results. The effect size was calculated for each test: E2R for the Kruskal-Wallis H test, Glass rank biserial correlation (rg) for the Mann-Whitney U test, and Cramér's V for the χ2 test. The value of p ≤0.05 was assumed to be a significant difference. In the study, it was shown that a higher overall quality of life and health satisfaction, as well as better results in the physical, psychological, and environmental domains, were achieved by female students who assessed their lifestyle as physically active in comparison to those physically inactive. Higher scores of overall quality of life and satisfaction with health were found among female students of physical education and people participating in physical recreation, who also achieved better results in the environmental domain. Female students aged 23-25 had a higher quality of life in the physical, psychological, and social domains. Having a partner or spouse had a positive effect on the quality of life of female students defined by the social domain. A higher overall quality of life and satisfaction with health were characteristic of people who were employed. In the search of factors positively influencing the quality of life of society, it seems necessary to promote a physically active lifestyle among students. The observed differences in the quality of life and health satisfaction of female students of selected majors require targeted programs and interventions that improve the quality of their lives at various stages of their studies. Such activities increase the health potential of the individual and society, not only in the biological, but also psychosocial dimension.

Physical Activity and Quality of Life of University Students, Their Parents, and Grandparents in Poland-Selected Determinants.

Physical activity is one of the factors conditioning human health. Research shows a positive impact of regular physical activity on the quality of human life. The aim of the study was to determine the relationship between the physical activity of university students, their parents, and their grandparents, and the overall quality of their lives in individual domains (physical, mental, social, environmental), as well as the perceived state of health in relation to selected determinants. The research included 1001 participants, including 253 students related to physical culture and health promotion studying at the University of Szczecin (faculties: physical education, tourism and recreation, public health, sports diagnostics), and their 336 parents and 412 grandparents. Purposive sampling was used to outline the determinants of quality of life and family factors in physical activity. The diagnostic survey was carried out based on the standardized WHOQOL-BREF (World Health Organization Quality of Life) questionnaire. Statistically significant differences were shown in the studied generations regarding the assessment of quality of life and satisfaction with health in the physical, psychological, social, and environmental domains. The oldest generation gave the lowest assessment of quality of life and was the least satisfied with their health regarding particular domains. Female students were more satisfied with their health compared to grandmothers and grandfathers, whereas male students compared to mothers and fathers. Fathers achieved the highest scores in the psychological and social domains, but, in case of the latter, differences were found between mothers' and fathers' assessments. Intergenerational differences were found in quality of life and the assessment of health status. Current participation in broadly understood physical culture was often a result of positive attitudes towards physical education and doing sport in the past, which meant higher scores in the physical domain each time. The study demonstrated that taking up physical activity impacted the quality of life and assessment of health in the past and currently.

Role of Polyinosinic:Polycytidylic Acid-Induced Maternal Immune Activation and Subsequent Immune Challenge in the Behaviour and Microglial Cell Trajectory in Adult Offspring: A Study of the Neurodevelopmental Model of Schizophrenia.

Multiple lines of evidence support the pathogenic role of maternal immune activation (MIA) in the occurrence of the schizophrenia-like disturbances in offspring. While in the brain the homeostatic role of neuron-microglia protein systems is well documented, the participation of the CX3CL1-CX3CR1 and CD200-CD200R dyads in the adverse impact of MIA often goes under-recognized. Therefore, in the present study, we examined the effect of MIA induced by polyinosinic:polycytidylic acid (Poly I:C) on the CX3CL1-CX3CR1 and CD200-CD200R axes, microglial trajectory (MhcII, Cd40, iNos, Il-1ß, Tnf-α, Il-6, Arg1, Igf-1, Tgf-ß and Il-4), and schizophrenia-like behaviour in adult male offspring of Sprague-Dawley rats. Additionally, according to the "two-hit" hypothesis of schizophrenia, we evaluated the influence of acute challenge with Poly I:C in adult prenatally MIA-exposed animals on the above parameters. In the present study, MIA evoked by Poly I:C injection in the late period of gestation led to the appearance of schizophrenia-like disturbances in adult offspring. Our results revealed the deficits manifested as a diminished number of aggressive interactions, presence of depressive-like episodes, and increase of exploratory activity, as well as a dichotomy in the sensorimotor gating in the prepulse inhibition (PPI) test expressed as two behavioural phenotypes (MIAPPI-low and MIAPPI-high). Furthermore, in the offspring rats subjected to a prenatal challenge (i.e., MIA) we noticed the lack of modulation of behavioural changes after the additional acute immune stimulus (Poly I:C) in adulthood. The important finding reported in this article is that MIA affects the expression and levels of the neuron-microglia proteins in the frontal cortex and hippocampus of adult offspring. We found that the changes in the CX3CL1-CX3CR1 axis could affect microglial trajectory, including decreased hippocampal mRNA level of MhcII and elevated cortical expression of Igf-1 in the MIAPPI-high animals and/or could cause the up-regulation of an inflammatory response (Il-6, Tnf-α, iNos) after the "second hit" in both examined brain regions and, at least in part, might differentiate behavioural disturbances in adult offspring. Consequently, the future effort to identify the biological background of these interactions in the Poly I:C-induced MIA model in Sprague-Dawley rats is desirable to unequivocally clarify this issue.

Chronic Fatigue Persists in a Significant Proportion of Female Patients After Transplantation for Primary Sclerosing Cholangitis.

Chronic fatigue and an impairment of general health-related quality of life (HRQoL) are frequently reported by patients with primary sclerosing cholangitis (PSC). Studies on patients with primary biliary cholangitis (PBC) suggest that, unlike pruritus, fatigue may not be ameliorated by liver transplantation (LT). However, there are few data regarding the assessment of fatigue before and after transplantation in PSC. To investigate the effect of LT on fatigue and HRQoL in patients with PSC, 81 patients with PSC (median age 33 years; 69% men) were prospectively enrolled in this study. The PBC-40 and Short Form 36 (SF-36) questionnaires were used for assessment before and twice after LT. A total of 26 patients who received a transplant for PBC were included as controls. The potential impact of the clinical and laboratory parameters was evaluated by univariate and multivariate analyses. Although in addition to other well-being indexes the median fatigue score improved after LT (P < 0.001), a detailed analysis demonstrated that fatigue persists in one-third of patients. A significant fatigue reduction was seen in men (P < 0.001) but not women (P = 0.25). Posttransplant fatigue did not depend on concomitant inflammatory bowel disease, laboratory indexes of cholestasis, or disease recurrence. In the multivariate regression model, female sex was the only independent covariate associated with persistent fatigue. In terms of other measures of HRQoL, LT caused a substantial improvement in the majority of SF-36 and PBC-40 domains. Recurrent PSC and unemployment negatively affected the well-being of patients. Patients who received a transplant for PSC had significantly better HRQoL than those patients with PBC. LT improves various measures of HRQoL, but it does not ameliorate fatigue in female patients with PSC.

The prenatal challenge with lipopolysaccharide and polyinosinic:polycytidylic acid disrupts CX3CL1-CX3CR1 and CD200-CD200R signalling in the brains of male rat offspring: a link to schizophrenia-like behaviours.

BACKGROUND: The bidirectional communication between neurons and microglia is fundamental for the homeostasis and biological function of the central nervous system. Maternal immune activation (MIA) is considered to be one of the factors affecting these interactions. Accordingly, MIA has been suggested to be involved in several neuropsychiatric diseases, including schizophrenia. The crucial regulatory systems for neuron-microglia crosstalk are the CX3CL1-CX3CR1 and CD200-CD200R axes. METHODS: We aimed to clarify the impact of MIA on CX3CL1-CX3CR1 and CD200-CD200R signalling pathways in the brains of male Wistar rats in early and adult life by employing two neurodevelopmental models of schizophrenia based on the prenatal challenge with lipopolysaccharide (LPS) and polyinosinic:polycytidylic acid (Poly I:C). We also examined the effect of MIA on the expression of microglial markers and the profile of cytokines released in the brains of young offspring, as well as the behaviour of adult animals. Moreover, we visualized the localization of ligand-receptor systems in the hippocampal regions (CA1, CA3 and DG) and the frontal cortex of young rats exposed to MIA. The differences between groups were analysed using Student's t test. RESULTS: We observed that MIA altered developmental trajectories in neuron-microglia communication in the brains of young offspring, as evidenced by the disruption of CX3CL1-CX3CR1 and/or CD200-CD200R axes. Our data demonstrated the presence of abnormalities after LPS-induced MIA in levels of Cd40, Il-1ß, Tnf-α, Arg1, Tgf-ß and Il-10, as well as IBA1, IL-1ß and IL-4, while after Poly I:C-generated MIA in levels of Cd40, iNos, Il-6, Tgf-ß, Il-10, and IBA1, IL-1ß, TNF-α, IL-6, TGF-ß and IL-4 early in the life of male animals. In adult male rats that experienced prenatal exposure to MIA, we observed behavioural changes resembling a schizophrenia-like phenotype. CONCLUSIONS: Our study provides evidence that altered CX3CL1-CX3CR1 and/or CD200-CD200R pathways, emerging after prenatal immune challenge with LPS and Poly I:C, might be involved in the aetiology of schizophrenia.

Physical exercise and catecholamines response: benefits and health risk: possible mechanisms.

Beneficial effect of regular moderate physical exercise (PE) and negative effect of severe exercise and/or overtraining as an activator of the sympathetic nervous system (SNS) have been shown in numerous aspects of human health, including reduced risk of cardiovascular disease, neurological disease, depression, and some types of cancer. Moderate-to-vigorous PE stimulates the SNS activation, releasing catecholamines (CATs) adrenaline, noradrenaline, dopamine that play an important regulatory and modulatory actions by affecting metabolic processes and the immune system. Summary of the dispersed literature in this area and explanation of the biological mechanisms operating between PE-CATs and the immune system would lead to a better understanding of the beneficial and negative effects of PE on health. This overview aimed to: demonstrate representative literature findings on the exercise released CATs levels, major functions performed by these hormones, their interactions with the immune system and their effects on carbohydrate and lipid metabolism. Also, mechanisms of cytotoxic free radicals and reactive oxygen species (ROS) generation during CATs oxidation, and molecular mechanisms of CATs response to exercise are discussed to demonstrate positive and negative on human health effects. Owing to the large body of the subject literature, we present a representative cross-section of the published studies in this area. The results show a significant role of CATs in carbohydrate and lipid metabolism, immunity and as generators of ROS, depending on PE intensity and duration. Further investigation of the PE-CATs relationship should validate CATs levels to optimize safe intensity and duration of exercise and individualize their prescription, considering CATs to be applied as markers for a dose of exercise. Also, a better understanding of the biological mechanisms is also needed.

Study on the Sequential Combination of Bioethanol and Biogas Production from Corn Straw.

The objective of this study was to obtain two types of fuels, i.e., bioethanol and biogas, in a sequential combination of biochemical processes from lignocellulosic biomass (corn straw). Waste from the agricultural sector containing lignocellulose structures was used to obtain bioethanol, while the post-fermentation (cellulose stillage) residue obtained from ethanol fermentation was a raw material for the production of high-power biogas in the methane fermentation process. The studies on obtaining ethanol from lignocellulosic substrate were based on the simultaneous saccharification and fermentation (SSF) method, which is a simultaneous hydrolysis of enzymatic cellulose and fermentation of the obtained sugars. Saccharomyces cerevisiae (D-2) in the form of yeast cream was used for bioethanol production. The yeast strain D-2 originated from the collection of the Institute of Agricultural and Food Biotechnology. Volatile compounds identified in the distillates were measured using gas chromatography with flame ionization detector (GC-FID). CH4 and CO2 contained in the biogas were analyzed using a gas chromatograph in isothermal conditions, equipped with thermal conductivity detector (katharometer) with incandescent fiber. Our results show that simultaneous saccharification and fermentation enables production of bioethanol from agricultural residues with management of cellulose stillage in the methane fermentation process.

Intensity of Health Behaviors in People Who Practice Combat Sports and Martial Arts.

Background: Health behaviors are associated with a healthy lifestyle, in which relative possibilities of choice play an important part. Athletes are a group of people who should particularly endeavor to have a health-oriented lifestyle. It is believed that combat sports (CS) and martial arts (MA) have an especially significant educational potential, connected with several desirable values which provide positive patterns of health behaviors. The aim of the work was to assess the intensity of health behaviors in athletes who practiced CS and MA in relation to the length of their training history, their age, sex, place of residence, education level, and financial situation. Methods: The research involved 441 men and women who practiced boxing (B), Brazilian ju-jitsu (BJJ), karate (K), mixed martial arts (MMA) and Muay Thai (MT). The average age of the subjects was 24.68 ± 8.24 years. The standardized Health Behavior Inventory (HBI) questionnaire and another questionnaire for a lifestyle survey were applied. Individual behaviors covered four areas: Correct eating habits (CEH), preventive behaviors (PB), positive mental attitude (PMA), and health practices (HP). The one-way analysis of variance (F-test) for independent groups was used (ANOVA). The effect size was calculated with Hedge's g for Student's t-test, and with Cramér's V for the χ2 test. The value of p ≤ 0.05 was assumed to be statistically significant. Results: CS and MA athletes presented a moderate level of health behaviors. The greater intensity of health behaviors (HBI and its categories) was found among B, K and MMA athletes, and the smaller among those who practiced MT. Correct eating habits (CEH) were characteristic of subjects who practiced every day and whose length of training history was 4-8 years. Greater intensity of preventive behaviors (PB) was observed among individuals aged under-19 years, who still studied. Greater intensity of health practices (HP) was found among those who exercised every day. Influence of financial situation was observed in relations to PMA. Conclusions: It seems that the existing educational potential of CS and MA was not fully realized in the studied population. Determining the place of health in the system of values of CS and MA athletes may be the basis for predicting health behaviors and developing health education programs.

Selected Healthy Behaviors and Quality of Life in People Who Practice Combat Sports and Martial Arts.

Background: The quality of life of a society is conditioned by many factors, and depends, among other things, on preferred behavior patterns. Combat sports (CS) and martial arts (MA) have a special educational potential in the area of shaping positive behavior patterns and transmitting moral values which could help reduce aggression in society. The aim of the work was to determine the relationship between health behaviors and the quality of life of people who practice combat sports and martial arts (CS and MA) recreationally, in addition to practicing other sports, and as competitors at the master level. Methods: The research embraced 543 people who practice combat sports and martial arts. Three groups were selected: recreational (n = 362), people who reconciled practicing various sports (n = 115), and competitors who practiced combat sports or martial arts at the master level (n = 66). The average age of the respondents was 24.49 ± 7.82. The standardized WHOQOL-BREF questionnaire and another questionnaire for a lifestyle survey were applied. The Kruskal-Wallis test was used to compare several independent samples. In the case of determining statistical significance of differences the Mann-Whitney test was employed, and for the qualitative data analyses the trait frequency and the independence chi-square test were used. The effect size was calculated for each test ( E R 2 , rg, Cramér's V). The value of p ≤ 0.05 was assumed to be statistically significant. Results: The highest quality of life (in the physical, psychological and environmental domains) was characteristic of the competitors, who practiced only combat sports and martial arts. They also displayed the most health-oriented behaviors. The surprising results were: lower quality of life in the assessment of nondrinkers and nonsmokers, and higher among people who were overweight. Conclusions: We have found positive correlations between practicing CS and MA, health behaviours and higher scores in quality of life self-evaluation, particularly where practitioners are exclusively focused on CS and MA and practice these at a competitive level. Our findings thus support the growing evidence that competitive level CS and MA are an effective means of improving people's quality of life. Future research needs to clarify whether CS and MA can also be recommended to recreational and non-competitive practitioners as a means to improve their subjective quality of life.

Correction to: Role of Chronic Administration of Antidepressant Drugs in the Prenatal Stress-Evoked Inflammatory Response in the Brain of Adult Offspring Rats: Involvement of the NLRP3 Inflammasome-Related Pathway.

The original version of this article unfortunately contained mistake in Acknowledgment.

Role of Chronic Administration of Antidepressant Drugs in the Prenatal Stress-Evoked Inflammatory Response in the Brain of Adult Offspring Rats: Involvement of the NLRP3 Inflammasome-Related Pathway.

Evidence indicates that adverse experiences in early life may be a factor for immune disturbances leading to the depression in adulthood. Recently, a pivotal role in the pathogenesis of depression has been assigned to the activation of the brain Nod-like receptor pyrin-containing 3 (NLRP3) inflammasome. We investigated the impact of chronic treatment with antidepressant drugs on the behavioral disturbances and the levels of proinflammatory factors in the hippocampus and frontal cortex of adult male rats after prenatal stress exposure. Next, we explored the involvement of the NLRP3 inflammasome-related pathways in the mechanism of antidepressant action. Our study confirmed that chronic antidepressant treatment attenuated depression-like disturbances and exerted an anxiolytic action. All antidepressants diminished the prenatal stress-induced increase in IL-1ß in both brain areas, while IL-18 only in the hippocampus. Moreover, tianeptine administration diminished the increase in CCR2 levels in both brain areas, while in the hippocampus, tianeptine, along with venlafaxine CCL2 and iNOS levels. Next, we observed that in the hippocampus, tianeptine and fluoxetine suppressed upregulation of TLR4. Furthermore, venlafaxine suppressed NFкB p65-subunit phosphorylation, while fluoxetine enhanced the IкB level. Importantly, in the hippocampus, all antidepressants normalized evoked by stress changes in caspase-1 level, while tianeptine and venlafaxine also affect the levels of ASC and NLRP3 subunits. Our results provide new evidence that chronic administration of antidepressants exerts anti-inflammatory effects more pronounced in the hippocampus, through suppression of the NLRP3 inflammasome activation. These effects are accompanied by an improvement in the behavioral dysfunctions evoked by prenatal stress.

Mitochondrial proteomics investigation of frontal cortex in an animal model of depression: Focus on chronic antidepressant drugs treatment.

BACKGROUND: Alteration in the brain mitochondrial functions have been suggested to participate, as a relevant factor, in the development of mental disorders. Therefore, the brain mitochondria may be a crucial therapeutic target in the course of depression. METHODS: Our goal was to find out the impact of two antidepressant drugs with various mechanisms of action - imipramine and fluoxetine, on the frontal cortex mitochondria-enriched fraction in an animal model of depression based on the prenatal stress procedure. RESULTS: Our results confirmed that the prenatal stress caused depressive-like disturbances in the adult offspring rats, which were normalized by the chronic imipramine and fluoxetine administration. For the first time, using 2D-LC-MS/MS, we demonstrated nine differentially expressed proteins after the imipramine administration. Of these proteins, the up-regulation of the 2',3'-cyclic-nucleotide 3'-phosphodiesterase enzyme and down-regulation of the Hypoxanthine-guanine phosphoribosyltransferase (HPRT), Ras-related proteins (Rap-1A and Rap-1B) and Transgelin-3 (NP25) were the most striking. In contrast, after the chronic fluoxetine treatment, we observed differential expression in five proteins, including the enhanced expression of component of pyruvate dehydrogenase complex and diminished of Glutathione S-transferase P (Gstp-1), as well as Maleylacetoacetate isomerase. CONCLUSIONS: These results overcome the interesting data that brain mitochondria in the frontal cortex may constitute the target for pharmacotherapy. The multifaceted profile of both antidepressant drugs action makes difficult to elucidate the exact mechanism of imipramine and fluoxetine action in the brain mitochondria. Further study of mitochondrial dysfunction in psychiatric disorders will be base to know the possible biological consequences of our observations.

The contribution of p53 and Y chromosome long arm genes to regulation of apoptosis in mouse testis.

Apoptosis of excessive or defective germ cells is a natural process occurring in mammalian testes. Tumour suppressor protein p53 is involved in this process both in developing and adult male gonads. Its contribution to testicular physiology is known to be modified by genetic background. The aim of this study was to evaluate the combined influence of the p53 and Y chromosome long arm genes on male germ cell apoptosis. Knockout of the transformation related protein 53 (Trp53) gene was introduced into congenic strains: B10.BR (intact Y chromosome) and B10.BR-Ydel (Y chromosome with a deletion in the long arm). The level of apoptosis in the testes of 19-day-old and 3-month-old male mice was determined using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ nick-end labelling (TUNEL) method. The study revealed that although p53 is involved in germ cell apoptosis in peripubertal testes, this process can also be mediated by p53-independent mechanisms. However, activation of p53-independent apoptotic pathways in the absence of the p53 protein requires engagement of the multicopy Yq genes and was not observed in gonads of B10.BR-Ydel-p53-/- males. The role of Yq genes in the regulation of testicular apoptosis seems to be restricted to the initial wave of spermatogenesis and is not evident in adult gonads. The study confirmed, instead, that p53 does participate in spontaneous apoptosis in mature testes.

Hyperforin Potentiates Antidepressant-Like Activity of Lanicemine in Mice.

N-methyl-D-aspartate receptor (NMDAR) modulators induce rapid and sustained antidepressant like-activity in rodents through a molecular mechanism of action that involves the activation of Ca2+ dependent signaling pathways. Moreover, ketamine, a global NMDAR antagonist is a potent, novel, and atypical drug that has been successfully used to treat major depressive disorder (MDD). However, because ketamine evokes unwanted side effects, alternative strategies have been developed for the treatment of depression. The objective of the present study was to determine the antidepressant effects of either a single dose of hyperforin or lanicemine vs. their combined effects in mice. Hyperforin modulates intracellular Ca2+ levels by activating Ca2+-conducting non-selective canonical transient receptor potential 6 channel (TRPC6) channels. Lanicemine, on the other hand, blocks NMDARs and regulates Ca2+ dependent processes. To evaluate the antidepressant-like activity of hyperforin and lanicemine, a set of in vivo (behavioral) and in vitro methods (western blotting, Ca2+ imaging studies, electrophysiological, and radioligand binding assays) was employed. Combined administration of hyperforin and lanicemine evoked long-lasting antidepressant-like effects in both naïve and chronic corticosterone-treated mice while also enhancing the expression of the synapsin I, GluA1 subunit, and brain derived neurotrophic factor (BDNF) proteins in the frontal cortex. In Ca2+ imaging studies, lanicemine enhanced Ca2+ influx induced by hyperforin. Moreover, compound such as MK-2206 (Akt kinase inhibitor) inhibited the antidepressant-like activity of hyperforin in the tail suspension test (TST). Hyperforin reversed disturbances induced by MK-801 in the novel object recognition (NOR) test and had no effects on NMDA currents and binding to NMDAR. Our results suggest that co-administration of hyperforin and lanicemine induces long-lasting antidepressant effects in mice and that both substances may have different molecular targets.

The Modulatory Properties of Chronic Antidepressant Drugs Treatment on the Brain Chemokine - Chemokine Receptor Network: A Molecular Study in an Animal Model of Depression.

An increasing number of studies indicate that the chemokine system may be the third major communication system of the brain. Therefore, the role of the chemokine system in the development of brain disorders, including depression, has been recently proposed. However, little is known about the impact of the administration of various antidepressant drugs on the brain chemokine - chemokine receptor axis. In the present study, we used an animal model of depression based on the prenatal stress procedure. We determined whether chronic treatment with tianeptine, venlafaxine, or fluoxetine influenced the evoked by prenatal stress procedure changes in the mRNA and protein levels of the homeostatic chemokines, CXCL12 (SDF-1α), CX3CL1 (fractalkine) and their receptors, in the hippocampus and frontal cortex. Moreover, the impact of mentioned antidepressants on the TGF-ß, a molecular pathway related to fractalkine receptor (CX3CR1), was explored. We found that prenatal stress caused anxiety and depressive-like disturbances in adult offspring rats, which were normalized by chronic antidepressant treatment. Furthermore, we showed the stress-evoked CXCL12 upregulation while CXCR4 downregulation in hippocampus and frontal cortex. CXCR7 expression was enhanced in frontal cortex but not hippocampus. Furthermore, the levels of CX3CL1 and CX3CR1 were diminished by prenatal stress in the both examined brain areas. The mentioned changes were normalized with various potency by chronic administration of tested antidepressants. All drugs in hippocampus, while tianeptine and venlafaxine in frontal cortex normalized the CXCL12 level in prenatally stressed offspring. Moreover, in hippocampus only fluoxetine enhanced CXCR4 level, while fluoxetine and tianeptine diminished CXCR7 level in frontal cortex. Additionally, the diminished by prenatal stress levels of CX3CL1 and CX3CR1 in the both examined brain areas were normalized by chronic tianeptine and partially fluoxetine administration. Tianeptine modulate also brain TGF-ß signaling in the prenatal stress-induced animal model of depression. Our results provide new evidence that not only prenatal stress-induced behavioral disturbances but also changes of CXCL12 and their receptor and at less extend in CX3CL1-CX3CR1 expression may be normalized by chronic antidepressant drug treatment. In particular, the effect on the CXCL12 and their CXCR4 and CXCR7 receptors requires additional studies to elucidate the possible biological consequences.