The sex steroid hormones (SSHs) such as testosterone, estradiol, progesterone, and their metabolites have important organizational and activational impacts on the brain during critical periods of brain development and in adulthood. A variety of slow and rapid mechanisms mediate both organizational and activational processes via intracellular or membrane receptors for SSHs. Physiological concentrations and distribution of SSHs in the brain result in normal brain development. Nevertheless, dysregulation of hormonal equilibrium may result in several mood disorders, including depressive disorders, later in adolescence or adulthood. Gender differences in cognitive abilities, emotions as well as the 2-3 times higher prevalence of depressive disorders in females, were already described. This implies that SSHs may play a role in the development of depressive disorders. In this review, we discuss preclinical and clinical studies linked to SSHs and development of depressive disorders. Our secondary aim includes a review of up-to-date knowledge about molecular mechanisms in the pathogenesis of depressive disorders. Understanding these molecular mechanisms might lead to significant treatment adjustments for patients with depressive disorders and to an amelioration of clinical outcomes for these patients. Nevertheless, the impact of SSHs on the brain in the context of the development of depressive disorders, progression, and treatment responsiveness is complex in nature, and depends upon several factors in concert such as gender, age, comorbidities, and general health conditions.
- MeSH
- depresivní poruchy * farmakoterapie MeSH
- emoce MeSH
- lidé MeSH
- mladiství MeSH
- mozek metabolismus MeSH
- pohlavní dimorfismus MeSH
- pohlavní steroidní hormony * metabolismus MeSH
- testosteron metabolismus MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Clinical studies show that hypogonadism in the aging male is associated with obesity and osteoporosis. Experimental studies are mostly conducted on relatively young adult animals and the induced hypogonadism lasts for a relatively short time. The present study aimed to describe the effect of long-term hypogonadism beginning in puberty on body composition, morphometry, and bone mineral density in aged male rats. Morphometric measurements and dual-energy X-ray absorptiometry were conducted at the age of 30 months on control and gonadectomized males. Long-term hypogonadism did not affect body weight, but led to a higher fat mass (by 26 %), lower lean mass (by 44 %), shorter body length (by 9 %), and anogenital distance (by 26 %), as well as to lower tail circumference (by 15 %) in comparison to control males. Lower bone mineral density (by 13 %) and bone mineral content (by 15 %) were observed in gonadectomized males. Results showing sarcopenic obesity and osteoporosis in this model of long-term hypogonadism might mimic the situation in aging males better than the widely used short-term hypogonadism induced in young animals. The morphometric analysis could potentially be a useful tool to study normal weight obesity without the need for specific equipment.
- MeSH
- adipozita MeSH
- časové faktory MeSH
- hypogonadismus krev patofyziologie MeSH
- kostní denzita MeSH
- modely nemocí na zvířatech MeSH
- obezita krev patofyziologie MeSH
- orchiektomie MeSH
- osteoporóza krev patofyziologie MeSH
- potkani Wistar MeSH
- sarkopenie krev patofyziologie MeSH
- složení těla * MeSH
- testosteron krev MeSH
- věkové faktory MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Neonatal hypoxic-ischemic encephalopathy is a disorder with heterogeneous manifestation due to asphyxia during perinatal period. It affects approximately 3-12 children per 1000 live births and cause death of 1 million neonates worldwide per year. Besides, motor disabilities, seizures, impaired muscle tone and epilepsy are few of the consequences of hypoxic-ischemic encephalopathy. Despite an extensive research effort regarding various treatment strategies, therapeutic hypothermia with intensive care unit supportive treatment remains the only approved method for neonates who have suffered from moderate to severe hypoxic-ischemic encephalopathy. However, these protocols are only partially effective given that many infants still suffer from severe brain damage. Thus, further research to systematically test promising neuroprotective treatments in combination with hypothermia is essential. In this review, we discussed the pathophysiology of hypoxic-ischemic encephalopathy and delved into different promising treatment modalities, such as melatonin and erythropoietin. However, preclinical studies and clinical trials are still needed to further elucidate the mechanisms of action of these modalities.
- MeSH
- erythropoetin terapeutické užití MeSH
- hypoxie komplikace farmakoterapie patofyziologie MeSH
- látky tlumící činnost CNS terapeutické užití MeSH
- lidé MeSH
- melatonin terapeutické užití MeSH
- mozková hypoxie a ischemie farmakoterapie etiologie patofyziologie MeSH
- novorozenec MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The study examined the morphological and long-term behavioral impacts of neonatal hypoxic-ischemic brain injury in a mouse model. We investigated the modification of different behavioral domains, such as spontaneous climbing, which represents fine motor skills. We also focused on sex-dependent differences during hypoxic-ischemic encephalopathy. The Rice-Vannucci model of hypoxia-ischemia was used, adjusted and adapted to 7-day-old C57BL/6NTac mice. The effects of induced hypoxia and ischemia were also studied separately. At postnatal day 60, mice underwent behavioral testing using the LABORAS apparatus. The perfusion for histological evaluation was performed one day after the behavioral analyses. In groups with separately induced hypoxia or ischemia, the observed alterations in behavior were not accompanied by morphological changes in the cortex or hippocampal formation. Female mice naturally climbed significantly more and hypoxic females reared less than hypoxic males (p<0.05). Male mice postnatally exposed to hypoxia-ischemia exhibited significantly lower vertical activity and higher horizontal activity (p<0.05). Mild hypoxic damage may not be morphologically detectable but may induce substantial behavioral changes in adult mice. There were significant differences between horizontal and vertical activity in reaction to hypoxia-ischemia. Our study indicates that the importance of behavioral testing is irreplaceable and may be reflected in neonatal medicine.
- MeSH
- biomechanika MeSH
- chov zvířat metody MeSH
- chování zvířat * MeSH
- mozková hypoxie a ischemie patofyziologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- novorozená zvířata MeSH
- poranění mozku patofyziologie MeSH
- sociální izolace * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Sex and gender matter in all aspects of life. Humans exhibit sexual dimorphism in anatomy, physiology, but also pathology. Many of the differences are due to sex chromosomes and, thus, genetics, other due to endocrine factors such as sex hormones, some are of social origin. Over the past decades, huge number of scientific studies have revealed striking sex differences of the human brain with remarkable behavioral and cognitive consequences. Prenatal and postnatal testosterone influence brain structures and functions, respectively. Cognitive sex differences include especially certain spatial and language tasks, but they also affect many other aspects of the neurotypical brain. Sex differences of the brain are also relevant for the pathogenesis of neuropsychiatric disorders such as autism spectrum disorders, which are much more prevalent in the male population. Structural dimorphism in the human brain was well-described, but recent controversies now question its importance. On the other hand, solid evidence exists regarding gender differences in several brain functions. This review tries to summarize the current understanding of the complexity of the effects of testosterone on brain with special focus on their role in the known sex differences in healthy individuals and people in the autism spectrum.
- MeSH
- autistická porucha metabolismus patologie MeSH
- kognice fyziologie MeSH
- lidé MeSH
- mozek účinky léků patologie MeSH
- pohlavní dimorfismus MeSH
- sexuální faktory MeSH
- testosteron metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Hypoxia is one of the major pathological factors affecting brain function. The aim of the present study was to describe the effect of neonatal hypobaric hypoxia on the behavior of rats and to analyze its effect on hippocampal neurodegeneration. Hypobaric hypoxia at a simulated altitude of 9000 m was induced for one hour in neonatal rat pups (PND7 and PND9) of both sexes. Subsequently, the rats underwent behavioral testing on PND25 and PND35 using a LABORAS apparatus to assess spontaneous behavior. Hypoxia did not cause any morphological damage in the hippocampus of rats. However, hypoxia on PND7 led to less horizontal locomotor activity both, in males (on PND25) and females (on PND35). Hypoxia on PND9 led to higher rearing in females on PND25. Hypoxic males exhibited higher grooming activity, while females lower grooming activity on PND35 following hypoxia induced on PND7. In females, hypoxia on PND9 resulted in higher grooming activity on PND25. Sex differences in the effect of hypoxia was observed on PND35, when hypoxic males compared to hypoxic females displayed more locomotor, rearing and grooming activity. Our data suggest that hypoxia on PND7 versus PND9 differentially affects locomotion and grooming later in adolescence and these effects are sex-dependent.
- MeSH
- hipokampus patologie MeSH
- hypoxie patologie psychologie MeSH
- lokomoce * MeSH
- novorozená zvířata MeSH
- péče o zevnějšek u zvířat * MeSH
- pohlavní dimorfismus MeSH
- potkani Wistar MeSH
- věkové faktory MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Laboratory mice in standard laboratory cages, besides horizontal and vertical locomotor activity, spontaneously display cage-bar related activities such as cage-grid climbing. Although, grid-climbing activity is one of the major components of spontaneous home-cage behavior of mice, its exact role is not fully understood. This study aimed to describe the sex-differences in coping with novelty and in spontaneous behavior of laboratory mice concerning the cage-climbing activity in an observer-independent open field test. Adult mice of both sexes (C57Bl/6NTac) underwent behavioral testing in LABORAS system. Female mice travelled significantly longer distance (by 30 %, p<0.05) and showed higher grid-climbing activity (by 50 %, p<0.05) than males. Based on our results, the grid-climbing is a sex-dependent activity of mice, however, its exact role remains to be elucidated.
- MeSH
- adaptace psychologická * MeSH
- lokomoce * MeSH
- myši inbrední C57BL MeSH
- pátrací chování * MeSH
- pohlavní dimorfismus * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Ulcerative colitis and Crohn's disease constitute the two main forms of inflammatory bowel disease. Prevalence of these diseases increases. In the present day, inadequate and inefficient therapy causes complications and frequent relapse. Extracellular DNA (ecDNA) is the DNA that is outside of cells and may be responsible for activation of the inflammatory response. To determine whether colitis is associated with higher concentration of ecDNA we used male mice of the C57BL/6 strain. Colitis was induced by 2% dextran sulphate sodium (DSS). After 7 days, mice exhibited considerable weight loss compared to the control group. Also, there was a higher stool consistency score and the colon was significantly shorter in comparison to the control group. Higher concentration of ecDNA was found in the DSS group. Interestingly, deoxyribonuclease activity was lower in the colon of the DSS group compared with the negative control. These findings may point to ecDNA as a potential pathogenetic factor and marker of inflammation.
- MeSH
- biologické markery metabolismus MeSH
- deoxyribonukleasy metabolismus MeSH
- DNA krev metabolismus MeSH
- gastrointestinální trakt enzymologie MeSH
- kolitida krev metabolismus patologie MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- síran dextranu MeSH
- tělesná hmotnost MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Cardiovascular diseases including hypertension are often associated with behavioural alterations. The aim of this study was to show, whether ivabradine, the blocker of If-channel in sinoatrial node, is able to modify the behaviour of rats in L-nitro-arginine methyl ester (L-NAME)-induced hypertension and to compare the effect of ivabradine with captopril and melatonin. 12-week-old male Wistar rats were divided into the following groups: controls, ivabradine (10 mg/kg/24 h), L-NAME (40 mg/kg/24 h), L-NAME + ivabradine, L-NAME + captopril (100 mg/kg/24 h), L-NAME + melatonin (10 mg/kg/24 h). Systolic blood pressure (SBP) and heart rate (HR) were measured by tail-cuff method once a week. The behaviour of rats was investigated during 23-hours in the phenotyper after four weeks of the treatment. Chronic administration of L-NAME induced hypertension without a change in HR. All tested substances partly prevented the increase of SBP, while ivabradine and melatonin also reduced HR. Ivabradine, captopril and melatonin reduced daily food intake, slightly decreased daily water intake and attenuated body weight gain. In L-NAME group, locomotor activity was enhanced by ivabradine, whereas exploratory behaviour was increased by melatonin and captopril. In conclusion, ivabradine, besides its potentially protective hemodynamic actions, does not seem to exert any disturbing effects on behaviour in L-NAME-induced hypertension in rats, while some of its effects were similar to captopril or melatonin. It is suggested that ivabradine used in cardiovascular indications is harmless regarding the effect on behaviour.
- MeSH
- antihypertenziva farmakologie MeSH
- benzazepiny farmakologie MeSH
- chování zvířat účinky léků MeSH
- hypertenze farmakoterapie metabolismus MeSH
- inhibitory ACE farmakologie MeSH
- kaptopril farmakologie MeSH
- krevní tlak účinky léků MeSH
- krysa rodu rattus MeSH
- lokomoce účinky léků MeSH
- melatonin farmakologie MeSH
- NG-nitroargininmethylester metabolismus MeSH
- oxid dusnatý metabolismus MeSH
- potkani Wistar MeSH
- srdeční frekvence účinky léků MeSH
- synthasa oxidu dusnatého metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH