RESUMEN
The incidence of autistic spectrum disorders (ASD) constantly increases in the world. Studying the mechanisms underlying ASD as well as searching for new therapeutic targets are crucial tasks. Many researchers agree that autism is a neurodevelopmental disorder. Clstn2-KO mouse strain with a knockout of calsyntenin 2 gene (Clstn2) is model for investigating ASD. This study aims to evaluate the social-conditioned place preference as well as density of dopaminergic (DA) neurons in the ventral tegmental area (VTA), which belongs to the brain reward system, in the males of the Clstn2-KO strain using wild type C57BL/6J males as controls. Social-conditioned place preference test evaluates a reward-dependent component of social behavior. The results of this test revealed differences between the Clstn2-KO and the control males, as the former did not value socializing with the familiar partner, spending equal time in the isolation- and socializing-associated compartments. The Clstn2-KO group entered both compartments more frequently, but spent less time in the socializing-associated compartment compared to the controls. By contrast, the control males of the C57BL/6J strain spent more time in socializing-associated compartment and less time in the compartment that was associated with loneness. At the same time, an increased number of DA and possibly GABA neurons labeled with antibodies against the type 2 dopamine receptor as well as against tyrosine hydroxylase were detected in the VTA of the Clstn2-KO mice. Thus, a change in social-conditioned place preference in Clstn2-KO mice as well as a higher number of neurons expressing type 2 dopamine receptors and tyrosine hydroxylase in the VTA, the key structure of the mesolimbic dopaminergic pathway, were observed.
RESUMEN
Autistic spectrum disorders (ASD) represent conditions starting in childhood, which are characterized by diff iculties with social interaction and communication, as well as non-typical and stereotyping models of behavior. The mechanisms and the origin of these disorders are not yet understood and thus far there is a lack of prophylactic measures for these disorders. The current study aims to estimate neuronal density in the prefrontal cortex and four hippocampal subf ields, i. e. СA1, СA2, СA3, and DG in Clstn2-KO mice as a genetic model of ASD. In addition, the level of neurogenesis was measured in the DG area of the hippocampus. This mouse strain was obtained by a knockout of the calsinthenin-2 gene (Clsnt2) in C57BL/6J mice; the latter (wild type) was used as controls. To estimate neuronal density, serial sections were prepared on a cryotome for the above-mentioned brain structures with the subsequent immunohistochemical labeling and confocal microscopy; the neuronal marker (anti-NeuN) was used as the primary antibody. In addition, neurogenesis was estimated in the DG region of the hippocampus; for this purpose, a primary antibody against doublecortin (anti-DCX) was used. In all cases Goat anti-rabbit IgG was used as the secondary antibody. The density of neurons in the CA1 region of the hippocampus was lower in Clstn2-KO mice of both sexes as compared with controls. Moreover, in males of both strains, neuronal density in this region was lower as compared to females. Besides, the differences between males and females were revealed in two other hippocampal regions. In the CA2 region, a lower density of neurons was observed in males of both strains, and in the CA3 region, a lower density of neurons was also observed in males as compared to females but only in C57BL/6J mice. No difference between the studied groups was revealed in neurogenesis, nor was it in neuronal density in the prefrontal cortex or DG hippocampal region. Our new f indings indicate that calsyntenin-2 regulates neuronal hippocampal density in subf ield-specif ic manner, suggesting that the CA1 neuronal subpopulation may represent a cellular target for early-life preventive therapy of ASD.
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Intact Disc1-L100P mice carrying a point mutation DISC1Rgsc1390 in the second exon of the DISC1 gene (genetic model of schizophrenia) differ from the parental C57BL/6NCrl strain by higher content of CD3+ T cells and reduced number of CD19+B cells in the peripheral blood and spleen. Analysis of T cell subpopulations revealed an increase in the number of CD3+CD4+ T helpers in the blood of mutant mice and a decrease in the level of CD3+CD8+ suppressor/cytotoxic T cells and CD3+CD4+CD25+ T-regulatory cells. The distribution pattern of inflammatory (IL-1ß, IL-2, IL-6, IL-17, IFNγ, and TNFα) and anti-inflammatory (IL-4, IL-10) cytokines specific for Disc1-L100P mice was revealed in the brain structures involved in the pathogenesis of schizophrenia. A possible implication of immune mechanisms in the development of schizophrenia-like endophenotype of Disc1-L100P mice is discussed.
Asunto(s)
Linfocitos B/inmunología , Encéfalo/inmunología , Proteínas del Tejido Nervioso/genética , Esquizofrenia/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Reguladores/inmunología , Animales , Linfocitos B/patología , Encéfalo/patología , Mapeo Encefálico , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Interferón gamma/genética , Interferón gamma/inmunología , Interleucina-10/genética , Interleucina-10/inmunología , Interleucina-17/genética , Interleucina-17/inmunología , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Interleucina-2/genética , Interleucina-2/inmunología , Interleucina-4/genética , Interleucina-4/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteínas del Tejido Nervioso/deficiencia , Proteínas del Tejido Nervioso/inmunología , Mutación Puntual , Esquizofrenia/genética , Esquizofrenia/patología , Transducción de Señal , Linfocitos T Colaboradores-Inductores/patología , Linfocitos T Reguladores/patología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Regenerative potential of multipotent mesenchymal stromal cells from the human umbilical cord (MMSC-UC) in the suspension and spheroid form was revealed during the progression of experimental small focal myocardial infarction in rats. In isoproterenol-induced myocardial infarction, foci of necrosis and inflammatory infiltrate and at later terms fibrosis foci were found mainly in the left ventricle of rat heart. In rats receiving MMSC-UC, destructive changes in the myocardium, fibrous scars, and inflammatory process were less pronounced. MMSC-UC also contributed to normalization of the morphofunctional parameters of the heart. Spheroids exhibited higher efficiency in comparison with cell suspension.
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Fibrosis Endomiocárdica/prevención & control , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/fisiología , Infarto del Miocardio/terapia , Regeneración/fisiología , Esferoides Celulares/trasplante , Animales , Modelos Animales de Enfermedad , Fibrosis Endomiocárdica/inducido químicamente , Fibrosis Endomiocárdica/patología , Fibrosis Endomiocárdica/fisiopatología , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/ultraestructura , Humanos , Isoproterenol/administración & dosificación , Masculino , Células Madre Mesenquimatosas/citología , Infarto del Miocardio/inducido químicamente , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Miocardio/patología , Miocardio/ultraestructura , Miocitos Cardíacos/patología , Miocitos Cardíacos/ultraestructura , Cultivo Primario de Células , Ratas , Ratas Wistar , Esferoides Celulares/citología , Esferoides Celulares/fisiología , Trasplante Heterólogo , Resultado del Tratamiento , Cordón Umbilical/citología , Cordón Umbilical/metabolismoRESUMEN
The DISC1 (disrupted in sÑhizophrenia 1) gene is associated with brain dysfunctions, which are involved in a variety of mental disorders, such as schizophrenia, depression and bipolar disorder. This is the first study to examine the immune parameters in Disc1-Q31L mice with a point mutation in the second exon of the DISC1 gene compared to mice of the C57BL/6NCrl strain (WT, wild type). A flow cytometry assay has shown that intact Disc1- Q31L mice differ from the WT strain by an increase in the percentage of CD3+ T cells, CD3+CD4+ Т helper cells and CD3+CD4+CD25+ T regulatory cells and a decrease in CD3+CD8+ T cytotoxic/suppressor cells in the peripheral blood. A multiplex analysis revealed differences in the content of cytokines in the brain structures of Disc1-Q31L mice compared to WT mice. The content of pro-inflammatory cytokines was increased in the frontal cortex (IL-6, IL- 17 and IFNγ) and striatum (IFNγ), and decreased in the hippocampus and hypothalamus. At the same time, the levels of IL-1ß were decreased in all structures being examined. In addition, the content of anti-inflammatory cytokines IL-4 was increased in the frontal cortex, while IL-10 amount was decreased in the hippocampus. Immune response to sheep red blood cells analyzed by the number of antibody-forming cells in the spleen was higher in Disc1-Q31L mice at the peak of the reaction than in WT mice. Thus, Disc1-Q31L mice are characterized by changes in the pattern of cytokines in the brain structures, an amplification of the peripheral T-cell link with an increase in the content of the subpopulations of CD3+CD4+ T helpers and CD3+CD4+CD25+ T regulatory cells, as well as elevated immune reactivity to antigen in the spleen.
RESUMEN
Second messengers cAMP and cGMP play an important role in synaptic plasticity and memory consolidation. The inhibitors of phosphodiesterases, enzymes hydrolyzing these cyclic nucleotides, are actively studied as potential drugs for the treatment of various cognitive disorders and depression. We studied the effects of a new inhibitor of phosphodiesterase 7 AGF2.20 on the formation of long-term potentiation in hippocampal slices. Administration of AGF2.20 (10 nM) in 90 min after weak tetanization prevented a decrease in the amplitude of excitatory post-synaptic potentials and stabilized long-term potentiation. These data attest to the involvement of phosphodiesterase 7 in the development of synaptic plasticity in the hippocampus. The inhibitor AGF2.20 is considered for the further analysis as a promising substance for the treatment of cognitive impairments.
Asunto(s)
Fosfodiesterasas de Nucleótidos Cíclicos Tipo 7/antagonistas & inhibidores , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 7/metabolismo , Inhibidores Enzimáticos/farmacología , Hipocampo/metabolismo , Potenciación a Largo Plazo/efectos de los fármacos , Animales , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Hipocampo/efectos de los fármacos , Técnicas In Vitro , Ratones , Ratones Endogámicos C57BL , Plasticidad Neuronal/efectos de los fármacosRESUMEN
The effect of everyday blue light (λ = 440-460 nm) on mitochondria of the retinal pigment epithelium of different age groups of Japanese quail was studied using electron microscopy, morphometric methods, and biochemical analysis. We have found a significant increase in the number of mitochondria, including those modified, mainly in young birds. In addition, cell metabolic activity increased in response to blue lighting. These changes are assumed to reflect an adaptive response of mitochondria aimed at neutralizing the phototoxic effect of blue light caused by accumulation of lipofuscin granules.
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Envejecimiento/metabolismo , Coturnix/metabolismo , Iluminación/efectos adversos , Lipofuscina/metabolismo , Mitocondrias/metabolismo , Epitelio Pigmentado de la Retina/metabolismo , Envejecimiento/patología , Animales , Femenino , Mitocondrias/patología , Epitelio Pigmentado de la Retina/patologíaRESUMEN
Calsyntenin-2 (Clstn2) is the synaptic protein that belongs to the super family of cadherins, playing an important role in learning and memory. We recently reported that Clstn2 knockout mice (Clstn2-KO) have a deficit of GABAergic interneurons coupled with hyperactivity and deficient spatial memory. Given, that impaired functioning of GABA receptors is linked to several psychopathologies, including anxiety and autism, we sought to further characterize Clstn2-KO mice with respect to emotional and social behavior. Clstn2-KO males and females were tested in the elevated plus-maze (EPM), open field (OF), forced swim test, social affiliation and recognition test, social transmission of food preference (STFP), dyadic social interactions and marble burying test. Clstn2-KO mice demonstrated high exploration and hyperactivity in the dimly lit EPM that affect anxiety parameters. In contrast, in a more adverse situation in the OF have increased emotionality in Clstn2-KO males, not females. Assessment of hyperactivity for prolong period in the OF showed that Clstn2-KO animals were able to decline their hyperactivity, but their ambulation still remained higher than in WT littermates. Additionally, Clstn2-KO mice expressed stereotyped behavior. Strikingly, analysis of social behavior identified deficient social motivation and social recognition only in Clstn2-KO males, but not in females. Further analysis of social communication in the STFP and direct observation of agonistic interactions confirmed the reduced social behavior in Clstn2-KO males. Altogether, current results showed Clstn2 gene and sex interactions on socio-emotional performance in mice, suggesting a possible role of calsyntenin2 in psychopathological mechanisms of autism.
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Proteínas de Unión al Calcio/deficiencia , Emociones/fisiología , Proteínas de la Membrana/deficiencia , Caracteres Sexuales , Conducta Social , Animales , Trastorno Autístico/metabolismo , Proteínas de Unión al Calcio/genética , Endofenotipos , Femenino , Preferencias Alimentarias , Aprendizaje , Masculino , Proteínas de la Membrana/genética , Ratones Noqueados , Actividad Motora , Reconocimiento en Psicología , OlfatoRESUMEN
Electron microscopic study of left ventricle cardiomyocytes and quantitative analysis of their mitochondriom was performed in rats exposed to tail-suspension, as a model of weightlessness effects, to artificial gravity produced by intermittent 2G centrifugation and a combination of these effects. It was found that the cardiomyocytes ultrastructure changed slightly after tail-suspension and after intermittent 2G influence, as well as under a combination of these effects. However, the number of intermitochondrial junctions increased significantly in the interfibrillar zone of cardiomyocytes under a combination of tail-suspension and intermittent 2G influence, which agrees with the cell hypertrophy described earlier.
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Gravitación , Ventrículos Cardíacos/citología , Miocitos Cardíacos/fisiología , Miocitos Cardíacos/ultraestructura , Simulación de Ingravidez , Animales , Centrifugación , Masculino , Microscopía Electrónica , Mitocondrias/ultraestructura , Ratas , Ratas WistarRESUMEN
Significant advances have been made in understanding the role of disrupted-in-schizophrenia-1 (DISC1) in the brain and accumulating findings suggest the possible implication of DISC1 in the regulation of dopamine (DA) function. A mutation in the second exon of DISC1 at L100P leads to the development of schizophrenia-related behavior in mutant mice (DISC1-L100P). We investigated here the role of DA in the expression of schizophrenia-related endophenotypes in the DISC1-L100P genetic mouse model. The mutated DISC1 resulted in facilitation of the psychostimulant effect of amphetamine in DISC1-L100P mutant mice assessed in the open field and prepulse inhibition (PPI) tests. Biochemical studies detected a 2.1-fold increase in the proportion of striatal D receptors without significant changes in DA release in vivo in the striatum of DISC1-L100P mutants in response to the low dose of amphetamine. The D(2) receptor antagonist haloperidol reversed the hyperactivity, PPI and latent inhibition (LI) deficits and blocked the psychostimulant effect of amphetamine in DISC1-L100P mutants. Taken together, our findings show the role of DISC1 in D(2) -related pathophysiological mechanism of schizophrenia, linking DISC1 with well-established DA hypothesis of schizophrenia.
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Dopamina/fisiología , Proteínas del Tejido Nervioso/genética , Esquizofrenia/genética , Esquizofrenia/fisiopatología , Estimulación Acústica , Anfetamina/antagonistas & inhibidores , Anfetamina/farmacología , Animales , Conducta Animal/efectos de los fármacos , Monoaminas Biogénicas/metabolismo , Química Encefálica/genética , Cromatografía Líquida de Alta Presión , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Antagonistas de Dopamina/farmacología , Inhibidores de Captación de Dopamina/antagonistas & inhibidores , Inhibidores de Captación de Dopamina/farmacología , Haloperidol/farmacología , Masculino , Ratones , Microdiálisis , Actividad Motora/fisiología , Mutación/genética , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/fisiología , Reflejo de Sobresalto/genética , Reflejo de Sobresalto/fisiología , Psicología del Esquizofrénico , Filtrado Sensorial/genética , Filtrado Sensorial/fisiologíaRESUMEN
This study was aimed to determine the effect of D2/D3 receptor antagonist sulpiride on the expression of immobility reflex ("pinch-test") and pinch-induced catalepsy ("bar-test") of CBA/Lac male mice depending on their social status ("aggressors" with repeated experience of victories or a "losers" with repeated experience of social defeats). Sulpiride (20 mg/kg, i.p.) was acutely administered to "aggressors" and "losers" after 10 and 20 daily social contacts (victories or social defeats) and to a control group of male mice. Repeated experience of social victories and defeats altered the immobility duration in both tests and modified the expression of the sulpiride effect. In the pinch-tets, the duration of immobility was longer in "loosers" than in "aggressors". In the bar-test, the pinch-induced catalepsy was more expressed in "losers" and "aggressors" as compared to control. Sulpiride was more effective in increasing immobility of"aggressors" and had a weaker effect on the control and "losers". Therefore, the effect of sulpiride is affected by the social status of the animals.
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Conducta Animal/fisiología , Catalepsia/fisiopatología , Dominación-Subordinación , Antagonistas de Dopamina/farmacología , Conducta Social , Sulpirida/farmacología , Animales , Conducta Animal/efectos de los fármacos , Masculino , RatonesRESUMEN
Activation of inflammation and enzyme cyclooxygenase with formation of proinflammatory prostaglandins is a key element of development of myocardial infarction in patients with acute coronary syndrome. Basing on literature data and own experience we suggested that single intravenous injection of 230 mg/kg of nonselective inhibitor of type 1 and 2 cyclooxygenase lornaxicam in the phase of initialization of inflammation 20 min after onset of ischemia would lead to reduction of myocardial infarction volume in rats in irreversible ischemia and ischemia with subsequent reperfusion. The conducted study allowed to reveal that administration of lornoxicam in recommended for human use dose lowered mortality of animals and increased number of capillaries per one cardiomyocyte in case of irreversible coronary artery occlusion. In ischemia-reperfusion as in irreversible myocardial ischemia lornoxicam reduced volume of necrosis and degree of thinning of left ventricular wall in the region of infarction, and lowered volume of connective tissue in periinfarction zone of the myocardium in remote period.
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Antiinflamatorios no Esteroideos/uso terapéutico , Infarto del Miocardio/prevención & control , Piroxicam/análogos & derivados , Daño por Reperfusión/complicaciones , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/patología , Masculino , Infarto del Miocardio/etiología , Infarto del Miocardio/patología , Piroxicam/administración & dosificación , Piroxicam/uso terapéutico , Ratas , Daño por Reperfusión/patología , Resultado del TratamientoRESUMEN
The exploratory activity towards a new object placed in the home cage was studied in CBA/Lac male mice after their repeated daily social victories and defeats. After 10 daily social defeats, submissive mice displayed a significantly declined exploration of a new object, whereas aggressive mice with experience of 10 daily victories expressed only a mild decrease in exploratory activity (as compared to control). Twenty daily social defeats almost completely abolished exploratory behavior in submissive mice, whereas 20 daily victories resulted in the increased exploration of a new object in aggressive mice. It is suggested that repeated social defeats associated with the negative psychoemotional state lead to the development of a pronounced exploratory motivational deficit. On the other hand, the experience of repeated daily aggression forms the enhanced motivational excitement that prevents a relevant response to a neutral stimulus.
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Conducta Animal/fisiología , Dominación-Subordinación , Conducta Exploratoria/fisiología , Estrés Psicológico/psicología , Agresión , Animales , Aprendizaje/fisiología , Masculino , Ratones , Ratones Endogámicos CBARESUMEN
The central nervous system (CNS) is rich in glycoconjugates, located on cell surface and in extracellular matrix. The products of Golgi UDP-GlcNAc:N-acetylglucosaminyltransferases (encoded by Mgat1, Mgat2, Mgat4 and Mgat5) act sequentially to generate the GlcNAc-branched complex-type N-glycans on glycoprotein receptors. While elimination of all the branched N-glycans in Mgat1(-/-) mouse embryos is lethal at neural tube fold stage, decreased branching is associated with late developmental defects similar to type 2 of congenital disorders of glycosylation, with developmental and psychomotor abnormalities. To study the role of complex-type N-glycans in brain function, we tested Mgat5(-/-) mice in a battery of neurological and behavioral tests. Despite the absence of tri- and tetra-antennary products, Mgat5(-/-) mice were not different from their wild-type littermates in physical and neurological assessments, anxiety level, startle reactivity and sensorimotor gating. However, they displayed a robust decrease in the immobility time in the forced swim test and the tail suspension test independent of locomotor activity, interpreted as a change in depression-like behavior. This effect was accentuated after chronic mild stress. Comparable increase in plasma corticosterone of Mgat5(+/+) and Mgat5(-/-) mice in response to acute stress shows an intact function of the hypothalamus-pituitary-adrenal axis. A change in social interactions was also observed. Our results indicate that Mgat5 modification of complex-type N-glycans on CNS glycoproteins is involved in the regulation of depression-like behavior.
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Depresión/genética , Depresión/prevención & control , N-Acetilglucosaminiltransferasas/deficiencia , Animales , Antidepresivos/farmacología , Conducta Animal , Depresión/enzimología , Emociones , Glicoproteínas/metabolismo , Aprendizaje por Laberinto/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Actividad Motora/efectos de los fármacos , Polisacáridos/metabolismo , Tiempo de Reacción , Estrés Psicológico/genética , NataciónRESUMEN
The GTF2IRD1 general transcription factor is a candidate for involvement in the varied cognitive and neurobehavioral symptoms of the microdeletion disorder, Williams-Beuren syndrome (WBS). We show that mice with heterozygous or homozygous disruption of Gtf2ird1 exhibit decreased fear and aggression and increased social behaviors. These findings are reminiscent of the hypersociability and diminished fear of strangers that are hallmarks of WBS. Other core features of WBS, such as increased anxiety and problems with spatial learning were not present in the targeted mice. Investigation of a possible neurochemical basis for the altered behaviors in these mice using high-performance liquid chromatography analysis showed increased levels of serotonin metabolites in several brain regions, including the amygdala, frontal cortex and parietal cortex. Serotonin levels have previously been implicated in fear and aggression, through modulation of the neural pathway connecting the prefrontal cortex and amygdala. These results suggest that hemizygosity for GTF2IRD1 may play a role in the complex behavioral phenotype seen in patients with WBS, either individually, or in combination with other genes, and that the GTF2I transcription factors may influence fear and social behavior through the alteration of neurochemical pathways.
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Agresión , Miedo , Proteínas Musculares/deficiencia , Proteínas Musculares/genética , Proteínas Nucleares/deficiencia , Proteínas Nucleares/genética , Serotonina/metabolismo , Transactivadores/deficiencia , Transactivadores/genética , Animales , Cruzamientos Genéticos , Señales (Psicología) , Genética Conductual , Aprendizaje por Laberinto , Ratones , Actividad Motora , ARN/genética , ARN/aislamiento & purificación , Conducta SocialRESUMEN
Semax, a member of ACTH-derived peptides family, has been employed in the treatment of acute ischemic stroke in patients. It decreased neurological deficit and reduced NO hyperproduction in the rat brain, caused by acute cerebral hypoperfusion. We suggested that semax is also able to protect rat heart from ischemic damage in acute myocardial infaction (AMI). AMI was induced by left coronary artery occlusion, myocardial ischemic area averaged 30 % of left ventricle. In 2 hours after coronary occlusion, the AMI group developed 11 % reduced mean arterial blood pressure and 48 % increased diastolic blood pressure in left ventricle in comparison with sham-operated control group. However, infusion of either dobutamine, which directly stimulates myocardial contractility, or sodium nitroprusside and phenylephrine, that change vascular resistance and thus cardiac afterload, did not reveal distinctions in hemodynamic parameters between groups. These data indicate absense or only moderate cardiac dysfunction in rats with AMI and are consistent wih morphometrical and histochemical studies that did not detect any necrotic or apoptotic (TUNEL-test) changes in left ventricular cardiomyocytes in spite of development of distinct ischemic disturbances of mitochondria and nuclear in about 50 % of cardiomyocytes in 2 hours after AMI. Semax (150 microg/kg), given i. p. 15 min and 2 hours after coronary occlusion, caused no effect on cardiac function, but completely prevented ischemia-induced ultrastructural changes of cardiomyocytes. This protective effect was accompanied by the ability of peptide to blunt the increase in plasma concentrations of nitrates, observed in AMI group.
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Hormona Adrenocorticotrópica/análogos & derivados , Infarto del Miocardio/tratamiento farmacológico , Fragmentos de Péptidos/uso terapéutico , Sustancias Protectoras/uso terapéutico , Hormona Adrenocorticotrópica/uso terapéutico , Animales , Cardiotónicos/farmacología , Dobutamina/farmacología , Corazón/efectos de los fármacos , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/ultraestructura , Masculino , Contracción Miocárdica , Infarto del Miocardio/patología , Miocardio/ultraestructura , Nitratos/sangre , Óxido Nítrico/antagonistas & inhibidores , Nitroprusiato/farmacología , Fenilefrina/farmacología , Ratas , Ratas EndogámicasRESUMEN
Semax, a member of ACTH-derived peptides family, was used in treatment of ischemic stroke in patients. It decreased neurological deficiency and reduced NO hyperproduction in the rat brain caused by acute cerebral hypoperfusion. We suggest that semax is also capable of protecting the rat heart from ischemic damage 28 days after myocardial infarction (MI) induced by left descendent coronary artery occlusion. Semax (150 microg/kg) was given i. p. in the operating day twice: 15 min and 2 hours after coronary occlusion, and once a day for the following 6 days. In 28 days after infarction, the MI group developed cardiac hypertrophy, cell growth was caused mainly by the increase of contractile filaments not supported by the appropriate mitochondrial growth that indicated an impaired energy supply of the cells. Moreover, cardiac hypertrophy was accompanied by decreased mean arterial blood pressure and cardiac contractile function and increased left ventricular end-diastolic pressure. Pharmacological change of cardiac afterload revealed that, in 28 days after MI, the rat heart was not able to change its contractile performance in response to either increase or decrease of systemic blood pressure, and as a result could not maintain its diastolic pressure. All these changes obviously reflect development of heart failure. Semax did not affect cardiac work but partially prevented end-diastolic pressure growth in left ventricle as well as ameliorated cardiomyocyte hypertrophy and disproportionate growth of contractile and mitochondrial apparatus, thus exerting beneficial effect on the left ventricular remodeling and heart failure development late after myocardial infarction.
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Hormona Adrenocorticotrópica/análogos & derivados , Cardiomiopatía Hipertrófica/prevención & control , Insuficiencia Cardíaca/prevención & control , Infarto del Miocardio , Fármacos Neuroprotectores/farmacología , Fragmentos de Péptidos/farmacología , Hormona Adrenocorticotrópica/farmacología , Animales , Cardiomiopatía Hipertrófica/etiología , Cardiomiopatía Hipertrófica/metabolismo , Cardiomiopatía Hipertrófica/patología , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/patología , Masculino , Mitocondrias Cardíacas/metabolismo , Mitocondrias Cardíacas/ultraestructura , Contracción Miocárdica/efectos de los fármacos , Infarto del Miocardio/complicaciones , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/ultraestructura , Ratas , Factores de TiempoRESUMEN
Chronic psychoemotional stress of social defeats produces development of experimental anxious depression in male mice similar to this disorder in humans. 5-HT and 5-HIAA levels, TPH and MAO A activities, 5-HT1A-receptors in different brain areas were investigated at different stages of development of experimental disorder. It has been shown that initial stage (3 days of social stress) is accompanied by increase of 5-HT level in some brain areas. Decreased 5-HIAA levels in the hippocampus, amygdala and nucleus accumbens were discovered at the stage of forming depression (10 days of social stress). Pharmacological desensitisation and decreased number of 5-HT1A-receptors were shown in frontal cortex and amygdala. At the stage of pronounced depression (20 days of stress), there were no differences in 5-HT and 5-HIAA levels in all brain areas (excluding hypothalamus) of depressive animals. However increased number of 5-HT1A-receptors and decreased affinity in amygdala and decreased TPH and MAOA activities in hippocampus were found in depressive mice. Hypofunction of serotonergic system is suggested at the stage of pronounced depression state in animals. Similar processes had place in brain dopaminergic systems. It is concluded that dynamic changes of brain monoaminergic activities accompany the development of anxious depression in animals. Various parameters of monoaminergic systems are differently changed depending on brain area, mediator system and stage of disorder.