Objective: to determine the morphological and functional parameters of athletes-junior wrestlers, determining their specialization, qualification and training in ontogenesis. Materials and methods: ...49 male junior athletes of the school of Olympic reserve engaged in martial arts in the GrecoRoman style for 6-10 years were examined. We used the Dorokhov R.N. (1994) technique of selection and early orientation in sports to determine the anthropometric temporal characteristics. Following functional indicators were determined: absolute and relative physical performance, aerobic performance, power index eagerly, type of vegetative regulation. Results: the majority of fighters teenagers CMS had mesosomal, microcorpulent, micromesomelic, micromesic and mesomacromembral somatotype. A comprehensive study of the functional parameters of the wrestlers showed that indicators of absolute and relative physical performance were higher in young men CMS and were respectively 1318.6±149.5 kg∙m/min and 19.3±2.5 kg∙m/(min∙kg). Aerobic performance was higher in adolescents and first-rank sportsmen: 51.8±9.36 ml/(min∙kg). The strength indices of the hands were higher in the young men's CMS and contributed to 70.6±6.37% for the right hand and 66.08±12.1% for the left hand, which was explained by the component body composition of the body of young men. Most of the wrestlers revealed moderate parasympathicotonia and amphotonic. Conclusions: the R.N. Dorokhova and V.G. Petrukhina (1994) method of somatotyping allows to differentiate athletes, involved in martial arts in the Greco-Roman style, into 3 levels of variation: dimensional, component and proportion and to determine their specialization, qualification and degree of training in ontogenesis.
Relevance of the research of modern climate change is beyond all doubts at the moment. Climate is, first of all, a significant share of any country’s resources. Losses due to global climate change ...can affect virtually all branches of economy and social aspects, including energy production, eco-systems, agriculture, forests, construction, transport, tourism etc.Climate change imposes certain mode of economy, a strategy of economy’s development years ahead. According to forecasts, for example the one of European environmental agency (EEA), one of the first “hostages” of climate change will be winter tourism and alpine skiing resorts. Climate change seriously influences incomes of countries and certain regions located in mountain areas and developing winter sports.Yet, forecasts of climatologists on modern climate change trends are ambiguous and sometimes controversial. For this reason definite scientific and practical interest is raised by research in climate change trends in mountain areas based on mostly state network of meteorological stations.
Relevance of the research of modern climate change is beyond all doubts at the moment. Climate is, first of all, a significant share of any country s resources. Losses due to global climate change ...can affect virtually all branches of economy and social aspects, including energy production, eco-systems, agriculture, forests, construction, transport, tourism etc.
Climate change imposes certain mode of economy, a strategy of economy s development years ahead. According to forecasts, for example the one of European environmental agency (EEA), one of the first hostages of climate change will be winter tourism and alpine skiing resorts. Climate change seriously influences incomes of countries and certain regions located in mountain areas and developing winter sports.
Yet, forecasts of climatologists on modern climate change trends are ambiguous and sometimes controversial. For this reason definite scientific and practical interest is raised by research in climate change trends in mountain areas based on mostly state network of meteorological stations.
The brain serotonin system in autism Rodnyy, Alexander Ya; Kondaurova, Elena M.; Tsybko, Anton S. ...
Reviews in the neurosciences,
01/2024, Letnik:
35, Številka:
1
Journal Article
Recenzirano
Autism spectrum disorders (ASDs) are among the most common neurodevelopmental diseases. These disorders are characterized by lack of social interaction, by repetitive behavior, and often anxiety and ...learning disabilities. The brain serotonin (5-HT) system is known to be crucially implicated in a wide range of physiological functions and in the control of different kinds of normal and pathological behavior. A growing number of studies indicate the involvement of the brain 5-HT system in the mechanisms underlying both ASD development and ASD-related behavioral disorders. There are some review papers describing the role of separate key players of the 5-HT system in an ASD and/or autistic-like behavior. In this review, we summarize existing data on the participation of all members of the brain 5-HT system, namely, 5-HT transporter, tryptophan hydroxylase 2, MAOA, and 5-HT receptors, in autism in human and various animal models. Additionally, we describe the most recent studies involving modern techniques for
regulation of gene expression that are aimed at identifying exact roles of 5-HT receptors, MAOA, and 5-HT transporter in the mechanisms underlying autistic-like behavior. Altogether, results of multiple research articles show that the brain 5-HT system intimately partakes in the control of some types of ASD-related behavior, and that specific changes in a function of a certain 5-HT receptor, transporter, and/or enzyme may normalize this aberrant behavior. These data give hope that some of clinically used 5-HT–related drugs have potential for ASD treatment.
Heterodimerization between 5‐HT7 and 5‐HT1A receptors seems to play an important role in the mechanism of depression and antidepressant drug action. It was suggested that the shift of the ratio ...between 5‐HT1A/5‐HT7 hetero‐ and 5‐HT1A/5‐HT1A homodimers in presynaptic neurons toward 5‐HT1A/5‐HT1A homodimers is one of the reasons of depression. Consequently, the artificial elevation of 5‐HT7 receptor number in presynaptic terminals might restore physiological homo‐/heterodimer ratio resulting in antidepressive effect. Here we showed that adeno‐associated virus (AAV)‐based 5‐HT7 receptor overexpression in the midbrain raphe nuclei area produced antidepressive effect in male mice of both C57Bl/6J and genetically predisposed to depressive‐like behavior ASC (antidepressant sensitive cataleptics) strains. These changes were accompanied by the elevation of 5‐HT7 receptor mRNA level in the frontal cortex of C57Bl/6J and its reduction in the hippocampus of ASC mice. The presence of engineered 5‐HT7 receptor in the midbrain of both mouse strains was further demonstrated. Importantly that 5‐HT7 receptor overexpression resulted in the reduction of 5‐HT1A receptor level in the membrane protein fraction from the midbrain samples of C57Bl/6J, but not ASC, mice. 5‐HT7 receptor overexpression caused an increase of 5‐HIAA/5‐HT ratio in the midbrain and the frontal cortex of C57Bl/6J and in all investigated brain structures of ASC mice. Thus, 5‐HT7 receptor overexpression in the raphe nuclei area affects brain 5‐HT system and causes antidepressive effect both in C57Bl/6J and in “depressive” ASC male mice. Obtained results indicate the involvement of 5‐HT7 receptor in the mechanisms underlying depressive behavior.
5‐HT7 receptor overexpression in the midbrain produces antidepressive effect in both “normal” C57Bl/6J and “depressive” ASC/Icg mice. This effect is accompanied by increased 5‐HT metabolism.
The mechanisms of autism are of extreme interest due to the high prevalence of this disorder in the human population. In this regard, special attention is given to the transcription factor Freud-1 ...(encoded by the
Cc2d1a
gene), which regulates numerous intracellular signaling pathways and acts as a silencer for 5-HT
1A
serotonin and D2 dopamine receptors. Disruption of the Freud-1 functions leads to the development of various psychopathologies. In this study, we found an increase in the expression of the
Cc2d1a
/Freud-1 gene in the hippocampus of BTBR mice (model of autistic-like behavior) in comparison with C57Bl/6J mice and examined how restoration of the
Cc2d1a
/Freud-1 expression in the hippocampus of BTBR mice affects their behavior, expression of 5-HT
1A
serotonin and D2 dopamine receptors, and CREB and NF-κB intracellular signaling pathways in these animals. Five weeks after administration of the adeno-associated viral vector (AAV) carrying the pAAV_H1-2_shRNA-Freud-1_Syn_EGFP plasmid encoding a small hairpin RNA (shRNA) that suppressed expression of the
Cc2d1a
/Freud-1 gene, we observed an elevation in the anxiety levels, as well as the increase in the escape latency and path length to the platform in the Morris water maze test, which was probably associated with a strengthening of the active stress avoidance strategy. However, the
Cc2d1a
/Freud-1 knockdown did not affect the spatial memory and phosphorylation of the CREB transcription factor, although such effect was found in C57Bl/6J mice in our previous study. These results suggest the impairments in the CREB-dependent effector pathway in BTBR mice, which may play an important role in the development of the autistic-like phenotype. The knockdown of
Cc2d1a
/Freud-1 in the hippocampus of BTBR mice did not affect expression of the 5-HT
1A
serotonin and D2 dopamine receptors and key NF-κB signaling genes (
Nfkb1
and
Rela
). Our data suggest that the transcription factor Freud-1 plays a significant role in the pathogenesis of anxiety and active stress avoidance in autism.
•BDNF system is involved in genetically defined fear-induced aggressive behavior.•Both BDNF mRNA and protein expression are increased in brain structures directly involved in regulation of aggressive ...behavior.•Truncated form of TrkB receptor is predominant in highly aggressive rats.
Brain-derived neurotrophic factor (BDNF), its precursor proBDNF, BDNF pro-peptide, BDNF mRNA levels, as well as TrkB and p75NTR receptors mRNA and protein levels, were studied in the brain of rats, selectively bred for more than 85 generations for either the high level or the lack of fear-induced aggressive behavior. Furthermore, we have found that rats of aggressive strain demonstrated both high level of aggression toward humans and increased amplitude of acoustic startle response compared to rats selectively bred for the lack of fear-induced aggression. Significant increase in the BDNF mRNA, mature BDNF and proBDNF protein levels in the raphe nuclei (RN), hippocampus (Hc), nucleus accumbens (NAcc), amygdala, striatum and hypothalamus (Ht) of aggressive rats was revealed. The BDNF/proBDNF ratio was significantly reduced in the Hc and NAcc of highly aggressive rats suggesting prevalence of the proBDNF in these structures. In the Hc and frontal cortex (FC) of aggressive rats, the level of the full-length TrkB (TrkB-FL) receptor form was decreased, whereas the truncated TrkB (TrkB-T) protein level was increased in the RN, FC, substantia nigra and Ht. The TrkB-FL/TrkB-T ratio was significantly decreased in highly aggressive rats suggesting TrkB-T is predominant in highly aggressive rats. The p75NTR expression was slightly changed in majority of studied brain structures of aggressive rats. The data indicate the BDNF system in the brain of aggressive and nonaggressive animals is extremely different at all levels, from transcription to reception, suggesting significant role of BDNF system in the development of highly aggressive phenotype.
Heterodimerization between 5-HT
and 5-HT
receptors seems to play an important role in the mechanism of depression and antidepressant drug action. It was suggested that the shift of the ratio between ...5-HT
/5-HT
hetero- and 5-HT
/5-HT
homodimers in presynaptic neurons toward 5-HT
/5-HT
homodimers is one of the reasons of depression. Consequently, the artificial elevation of 5-HT
receptor number in presynaptic terminals might restore physiological homo-/heterodimer ratio resulting in antidepressive effect. Here we showed that adeno-associated virus (AAV)-based 5-HT
receptor overexpression in the midbrain raphe nuclei area produced antidepressive effect in male mice of both C57Bl/6J and genetically predisposed to depressive-like behavior ASC (antidepressant sensitive cataleptics) strains. These changes were accompanied by the elevation of 5-HT
receptor mRNA level in the frontal cortex of C57Bl/6J and its reduction in the hippocampus of ASC mice. The presence of engineered 5-HT
receptor in the midbrain of both mouse strains was further demonstrated. Importantly that 5-HT
receptor overexpression resulted in the reduction of 5-HT
receptor level in the membrane protein fraction from the midbrain samples of C57Bl/6J, but not ASC, mice. 5-HT
receptor overexpression caused an increase of 5-HIAA/5-HT ratio in the midbrain and the frontal cortex of C57Bl/6J and in all investigated brain structures of ASC mice. Thus, 5-HT
receptor overexpression in the raphe nuclei area affects brain 5-HT system and causes antidepressive effect both in C57Bl/6J and in "depressive" ASC male mice. Obtained results indicate the involvement of 5-HT
receptor in the mechanisms underlying depressive behavior.
Intracerebroventricular administration of selective agonist of serotonin 5-HT7 receptor LP44 (4-2-(methylthio)phenyl-N-(1,2,3,4-tetrahydro-1-naphthalenyl)-1-pyperasinehexanamide hydrochloride; 10.3, ...20.5 or 41.0 nmol) produced considerable hypothermic response in CBA/Lac mice. LP44-induced (20.5 nmol) hypothermia was significantly attenuated by the selective 5-HT7 receptor antagonist SB 269970 (16.1 fmol, i.c.v.) pretreatment. At the same time, intraperitoneal administration of LP44 in a wide range of doses 1.0, 2.0 or 10.0 mg/kg (2.0, 4.0, 20.0 μmol/kg) did not cause considerable hypothermic response. These findings indicate the implication of central, rather than peripheral 5-HT7 receptors in the regulation of hypothermia. The comparison of LP44-induced (20.5 nmol) hypothermic reaction in eight inbred mouse strains (DBA/2J, CBA/Lac, C57BL/6, BALB/c, ICR, AKR/J, C3H and Asn) was performed and a significant effect of genotype was found.
In the same eight mouse strains, functional activity of 5-HT1A and 5-HT3 receptors was studied. The comparison of hypothermic responses produced by 5-HT7 receptor agonist LP44 (20.5 nmol, i.c.v.) and 5-HT1A receptor agonist 8-OH-DPAT 1.0 mg/kg, i.p. (3.0 μmol/kg), 5-HT3 receptor agonist m-CPBG (40.0 nmol, i.c.v.) did not reveal considerable interstrain correlations between 5-HT7 and 5-HT1A or 5-HT3 receptor-induced hypothermia. The selective 5-HT7 receptor antagonist SB 269970 (16.1 fmol, i.c.v.) failed to attenuate the hypothermic effect of 8-OH-DPAT 1.0 mg/kg, i.p. (3.0 μmol/kg) and m-CPBG (40.0 nmol, i.c.v.) indicating that the brain 5-HT7 receptor is not involved in the hypothermic effects of 8-OH-DPAT or m-CPBG. The obtained results suggest that the central 5-HT7 receptor plays an essential role in the mediation of thermoregulation independent of 5-HT1A and 5-HT3 receptors.
► Central but not peripheral Htr7 agonist LP44 injection produced hypothermia in mice. ► Effect of genotype in LP44-induced hypothermia in mice was found. ► No interstrain correlation between Htr7 and Htr1A, Htr3-induced hypothermia was found. ► Htr7 antagonist failed to attenuate Htr1A and Htr3-induced hypothermia. ► Central Htr7 implicated in the thermoregulation independent on Htr1A and Htr3.
The influence of genetic background on sensitivity to drugs represents a topical problem of personalized medicine. Here, we investigated the effect of chronic (20 mg/kg, 14 days, i.p.) antidepressant ...fluoxetine treatment on recombinant B6-M76C mice, differed from control B6-M76B mice by CBA-derived 102.73–110.56 Mbp fragment of chromosome 13 and characterized by altered sensitivity of 5-HT1A receptors to chronic 8-OH-DPAT administration and higher 5-HT1A receptor mRNA levels in the frontal cortex and hippocampus. Significant changes in the effects of fluoxetine treatment on behavior and brain 5-HT system in recombinant B6-M76C mice were revealed. In contrast to B6-M76B mice, in B6-M76C mice, fluoxetine produced pro-depressive effects, assessed in a forced swim test. Fluoxetine decreased 5-HT1A receptor mRNA levels in the cortex and hippocampus, reduced 5-HT1A receptor protein levels and increased receptor silencer Freud-1 protein levels in the hippocampus of B6-M76C mice. Fluoxetine increased mRNA levels of the gene encoding key enzyme for 5-HT synthesis in the brain, tryptophan hydroxylase-2, but decreased tryptophan hydroxylase-2 protein levels in the midbrain of B6-M76B mice. These changes were accompanied by increased expression of the 5-HT transporter gene. Fluoxetine reduced 5-HT and 5-HIAA levels in cortex, hippocampus and midbrain of B6-M76B and in cortex and midbrain of B6-M76C; mice. These data demonstrate that changes in genetic background may have a dramatic effect on sensitivity to classic antidepressants from the Selective Serotonin Reuptake Inhibitors family. Additionally, the results provide new evidence confirming our idea on the disrupted functioning of 5-HT1A autoreceptors in the brains of B6-M76C mice, suggesting these mice as a model of antidepressant resistance.
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