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Biomedical subjects

A V Kulikov

Publications and source records attributed to A V Kulikov.

At least 19 recordsLinked to original sources

Association between Tph2 gene polymorphism, brain tryptophan hydroxylase activity and aggressiveness in mouse strains.

The brain neurotransmitter serotonin is involved in the regulation of aggressive behavior. The main factor determining the brain serotonin level is the activity of the rate-limiting enzyme in the biosynthesis of the neurotransmitter--tryptophan hydroxylase isoform (TPH) 2 encoded by the Tph2 gene. Recently the C1473G single-nucleotide polymorphism in the Tph2 gene was reported. Here we study the C1473G polymorphism in 10 inbred mouse strains (C57BL/6J, AKR/J, DD/He, C3H/HeJ, YT/Y, BALB/cJLac, CC57BR/Mv and A/He) and demonstrate the association of the polymorphism with brain TPH activity and intermale aggressiveness. TPH activity in the midbrain of mice homozygous for the 1473C allele was higher than that in mice carrying 1473G alleles. A close association of the 1473C allele with increased number of attacks towards another male was found. The results support a link between the C1473G polymorphism in Tph2 gene, tryptophan hydroxylase activity and intensity of intermale aggression.

Aggression↗

[Effect of experimental elevation and decrease of thyroxine level on catalepsy in rats].

Thyroid dysfunction is associated with mental disorders. The present study was aimed to reveal the effects of experimental decrease and increase of thyroxine level on expression of two types of extensive freezing: spontaneous and pinch-induced catalepsy, in Wistar rat males. Chronic administration of thyroxine synthesis inhibitor, propylthiouracil (5 mg/kg/day, 28 days), markedly decreased plasma hormone level and at the same time produced a significant increase in percentage of spontaneously cataleptic animals and immobility time, but had no effect on the expression of pinch-induced catalepsy. On the contrary, chronic thyroxin (0.1 mg/kg/day, 28 days) treatment produced no effect on spontaneous catalepsy expression, although it significantly increased percentage of cataleptic animals and immobility time of pinch-induced catalepsy. The results suggest that both the thyroid hormone deficit and excess provoke catalepsy in rats but enhance different forms of freezing reaction.

Animals↗

[Hereditary catalepsy: genetic and molecular mechanisms of catalepsy in mice].

The results of experiments on the inheritance and neurobiological mechanism of high predisposition to tonic immobility (catalepsy) in CBA mice are discussed. Genetic analysis has demonstrated a monogenic inheritance of the predisposition to catalepsy. A set of polymorphic microsatellite markers has been used to demonstrate that the predisposition to catalepsy is linked to the distal fragment of mouse chromosome 13, which contains the gene of the 5-HT1A-serotonin receptor. Pharmacological and biochemical evidence for the association between hereditary catalepsy and 5-HT1A-receptor dysfunction are presented. The use of CBA mice for studying the mechanisms of depression and the effects of antidepressants is discussed.

Animals↗

[Catatonia or depression: the GC rat strain as an animal model of psychopathology].

The utility of "incomplete" genetic animal models of human diseases, in particular, psychoses, is discussed. The GC rat strain selected for predisposition to cataleptic reactions is described. It is shown that in many of their characteristics, GC rats are similar to schizophrenic and depressive patients. A possibility that akinetic catatonic states and depressions, hyperkinetic catatonic states and mania share common mechanisms is discussed. It is hypothesized that the GC strain may be an incomplete model of the common genetic and pathogenetic core of schizophrenic substuporous states and depression, which suggests the importance of returning to the issue of a unitary psychosis (Einheitpsychosis).

Animals↗

[Polymorphism of the serotonin system genes in some Finno-Ugric populations].

Polymorphic sites in the genes encoding monoamine oxidase A (MAO-A), serotonin transporter (hSERT) and 5-HT2A receptor were typed in Khant and Komi ethnic groups with the purpose of revealing possible interpopulation differences in genotype and allele frequencies. No statistically significant differences in the hSERT and 5-HT2A gene frequencies were detected. At the same time, the populations examined had statistically significantly different MAO-A genotype and allele frequencies. These results obtained indicate the prevalence of the site gain alleles of the EcoRV and Fnu4HI RFLP loci at the MAO-A gene in Komis and the of the corresponding site loss alleles in Khants.

Alleles↗

Expression of prolactin receptors in human liver during cholestasis of different etiology and secondary liver cancer.

Indirect immunoperoxidase assay and computer analysis of photographic images revealed more intensive expression of prolactin receptors in hepatocytes of women compared to men. The intensity of expression was maximum in secondary liver cancer, high in obstructive jaundice of different etiology, and less pronounced in cholelithiasis. The expression of prolactin receptors in cholangiocytes was higher than in hepatocytes and was maximum during obstructive jaundice of different etiology. Cells of secondary tumors were characterized by low expression, while distant hepatocytes most intensively expressed prolactin receptors.

Adult↗

[Testing linkage hypothesis in hybrid analysis of alternatively distributed behavioral traits with incomplete penetrance].

The use of polymorphic microsatellite markers for mapping alternatively distributed behavioral traits with incomplete penetrance was studied with special reference to inheritance of predisposition to catalepsy in mice. Using only backcrosses as a segregating population, the major gene for catalepsy was with high likelihood mapped to region 30-75 cM of murine chromosome 13. It was also established that this gene determines 20% of the trait penetrance whereas the remaining 31% of the observed penetrance are accounted for by numerous polygenes.

Animals↗

[The annual involution and regeneration of the thymus in hibernating animals and perspectives of its studies in gerontology and stem cell proliferation].

Data on a unique phenomenon of annual involution and neogenesis of thymus gland in hibernating animals are reviewed. In accordance with morphological findings, the annual thymus involution in hibernating animals is close to the age-dependent thymus involution occurring in all mammals once in a lifetime. In opposite, thymus involution in hibernating animals is totally different from the accidental involution. During hibernation, the thymus tissue is substituted by the brown fat tissue. In the spring, thymus gland neogenesis stats with intensive growth of epithelial tissue followed by lymphocyte infiltration and exhaustion of brown tissue. Morphological changes in the thymus gland within the annual cycle were compared with seasonal dynamics of structural and functional changes in peripheral lymphoid organs (spleen, lymphoglandular, peritoneal fluid). A general regularity was observed involving a decreased functional activity of immune cells in autumn, its sharp depression during winter hibernation, and obvious increase in summer with the onset of a season of animal activity. It is supposed that a sharp increase in the tumor necrosis factor (TNF) production observed during short-term awakenings in winter may serve an important link in this unique immune adaptation mechanism. The season changes in cellular TNF secretion suggest a mobilization of protective resources in hibernating animals in autumn and winter, i.e. in seasons when the thymus gland activity is depressed. The annual involution of thymus gland cannot be related to droppings in the environmental or body temperatures, as it comes long before their fall. Additionally, it is not related to ageing, as it occurs already in young hibernating animals. The role of hormones, including melatonine and corticosteroids, in mechanisms regulating thymus gland involution in hibernating animals is discussed.

Adaptation, Physiological↗

Effects of thyroid hormone deficiency on behavior in rat strains with different predisposition to catalepsy.

The effects of thyroidectomy on anxiety-related behavior in the elevated plus-maze test, locomotor activity, and defecation in the open-field test and duration of cataleptic freezing were studied in rats of two strains differing in predisposition to catalepsy: cataleptic strain GC and its ancestor strain Wistar. Total thyroxine level was significantly decreased in control GC rats compared to that in control Wistar rats. Control Wistar and GC rats did not differ either in the percentages of open-arm entries or the time spent therein in the elevated plus-maze test or in defecation score in the open-field test. At the same time, control Wistar rats showed more locomotor activity compared to control GC rats in the open-field test. Thyroid hormone deficiency did not affect the percentages of open-arm entries and the time spent therein in the elevated plus-maze test as well as defecation score in both strains. Thyroidectomy did not alter significantly locomotor activity in Wistar rats, but produced a nearly twofold increase in locomotor activity in GC rats. The most important finding is that thyroidectomy significantly increased the expression of catalepsy in Wistar rats, which points to a role of thyroid hormones in the regulation of predisposition to cataleptic reaction.

Analysis of Variance↗

Effect of chronic administration of imipramine on 2A-serotonin receptor mRNA in brain cortex of rats predisposed and resistant to catalepsy.

Rats selected by predisposition to catalepsy showed decreased level of 2A-serotonin receptor mRNA in the frontal cortex in comparison with Wistar rats (p<0.05). Chronic administration of tricyclic antidepressant imipramine hydrochloride 2-fold increased the content of receptor mRNA in genetically cataleptic rats (p<0.001) and did not change this parameter in Wistar rats. These results prompted us to revise current notion on the mechanisms of chronic effect of imipramine on 2A-serotonin receptors.

Animals↗

Thyroid hormone deficiency determines predisposition to catalepsy in rats.

The role of thyroid hormones in predisposition to cataleptic reaction was investigated. GC rats with genetic predisposition to catalepsy were characterized by decreased serum thyroxin content in comparison with Wistar rats. Thyroidectomy even more reduced the blood concentration of thyroxin in GC rats 30 days postoperation and augmented predisposition to catalepsy in both rat strains.

Animals↗

[Effect of hypothyroidism on 5-HT1A-, 5-HT2A-receptors and serotonin transporter in the rat brain].

Effects of thyroid hormone deficiency on 5-HT1A receptors, 5-HT2A receptors and serotonin transporter in the brain were studied in thyroidectomised Wistar rats receiving an iodine-free diet and receiving 15 micrograms/kg of thyroxine for 21 days. Binding of 3H-8-OH-DPAT to 5-HT1A receptors and 3H-cytalopram to serotonin transporter were unchanged in hypothyroid rats as compared to the control. 3H-ketanserin binding to 5-HT2A receptors was significantly decreased in the frontal cortex in hypothyroid rats. The cortical 3H-ketanserin binding in thyroidectomised rats was normalised after thyroxine replacement. The data suggest that the decrease in the cortical 5-HT2A receptors is the main consequence of impairing effect of hypothyroidism on serotonin neurotransmission.

Animals↗

[Effect of 5HT2 receptor blockade on the startle reflex and its prepulse inhibition in mice and rats of various strains].

Effects of 5-HT2 receptor blockade on the amplitude of startle reflex, induced by an unexpected sound, and on its prepulse inhibition (PPI) were studied on mice of CBA strain and rats of Wistar and the genetically predisposed to catalepsy (GC) strains. The effect was dependent on type and dose of 5-HT2 antagonist used: 5-HT2A antagonist ketanserin increased startle amplitude at the dose of 0.5 mg/kg and decreased it at the dose of 2 mg/kg. Mixed 5-HT2A/2C antagonist ritanserin (0.1 and 0.2 mg/kg) markedly increased startle in mice. Ketanserin and cyproheptadine produced opposite effects on startle reflex in rats with inherited neuropathology and in rats with normal genotype: marked decrease in GC rats and increase in Wistar rats was shown. Ketanserin and cyproheptadine produced a pronounced potentiation of PPI in mice and rats of both strains, ritanserin was ineffective. Results suggest 5-HT2 receptors implication in both startle and PPI regulation with 5-HT2C receptors in startle response and 5-HT2A in PPI predominant involvement.

Animals↗

Binding of platinum-diaminonitroxyl complexes to animal DNA.

Reaction of PtII(DAPO)X2 complexes (where DAPO is trans-3,4-diamino-2,2,6,6-tetramethylpiperidine-1-oxyl, X2 = (NO3)2, oxalato (Ox) or 1,1-cyclobutanedicarboxylato (Cbdca)) with a bovine spleen DNA in 0.01 M NaHCO3 at 37 degrees C for 24 h gives rise to formation of platinated DNA. The [bound PtII(DAPO)]/[nucleotide] ratio (r) depends on the initial ratio of the reagents and on the nature of leaving ligands X. Nitroxyl-nitroxyl distances in platinated DNA determined by the ESR suggest that at r > or = 0.1 PtII(DAPO) fragments are uniformly attached to DNA. But at lower r, the thermal characteristics of modified DNA (melting temperature Tm, melting range width delta T) and the guanine-to-adenine platination degree ratios GPt/APt imply that the nature of leaving ligands X affect the selectivity of DNA platination. At r > or = 0.1, nitroxyl groups can approach each other so close that, in an acidic medium, the electron transfer from one nitroxyl group to another becomes possible, and the nitroxyls readily disproportionate to diamagnetic products. Correlation time of nitroxyl rotation in PtII(DAPO)-DNA adducts is approximately 10(-8) s, which is related to predominantly bifunctional bonding of PtII(DAPO) with DNA. Platination-induced distortion of DNA was evidenced by changes in Tm, delta T and degree of hyperchromicity H. The major part of adducts form the intrastrand cross-links which destabilize the structure of DNA duplex. The interstrand PtII(DAPO) cross-linking (approximately 1% of the adducts) facilitates renaturation of despiralized DNA molecules upon cooling. Two types of PtII(DAPO)-DNA adducts are revealed, which differ substantially in their rates of deplatination with NaCN. ESR, electron spin resonance; r, degree of modification; cisplatin, cis-diamminedichloroplatinum(II); Tm, melting temperature; delta T, melting range width; H, degree of hyperchromicity; R, degree of renaturation; AAS, atomic absorption spectroscopy; HPLC, high performance liquid chromatography.

Animals↗

Tissue transplantation as a compensation for deleterious effects of ageing, radiation, diabetes, and craniocerebral trauma.

The presence of blood-brain and blood-ocular barriers allows the transplantation of various biological tissues into the brain and the anterior eye chamber without acute immune rejection. Tissue grafting into the immuno-privileged areas (brain, anterior eye chamber) allows its long-term functioning without immuno-suppression. This method was shown to be effective in compensating for the deleterious effects of ageing, radiation, diabetes, and craniocerebral trauma.

Aging↗