RESUMO
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.
Assuntos
Linfócitos B/imunologia , Encéfalo/imunologia , Proteínas do Tecido Nervoso/genética , Esquizofrenia/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologia , Animais , Linfócitos B/patologia , Encéfalo/patologia , Mapeamento Encefálico , Modelos Animais de Doenças , Regulação da Expressão Gênica , Interferon gama/genética , Interferon gama/imunologia , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-17/genética , Interleucina-17/imunologia , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-2/genética , Interleucina-2/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas do Tecido Nervoso/deficiência , Proteínas do Tecido Nervoso/imunologia , Mutação Puntual , Esquizofrenia/genética , Esquizofrenia/patologia , Transdução de Sinais , Linfócitos T Auxiliares-Indutores/patologia , Linfócitos T Reguladores/patologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
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.
Assuntos
Fibrose Endomiocárdica/prevenção & controle , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/fisiologia , Infarto do Miocárdio/terapia , Regeneração/fisiologia , Esferoides Celulares/transplante , Animais , Modelos Animais de Doenças , Fibrose Endomiocárdica/induzido quimicamente , Fibrose Endomiocárdica/patologia , Fibrose Endomiocárdica/fisiopatologia , Ventrículos do Coração/patologia , Ventrículos do Coração/ultraestrutura , Humanos , Isoproterenol/administração & dosagem , Masculino , Células-Tronco Mesenquimais/citologia , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/patologia , Miocárdio/ultraestrutura , Miócitos Cardíacos/patologia , Miócitos Cardíacos/ultraestrutura , Cultura Primária de Células , Ratos , Ratos Wistar , Esferoides Celulares/citologia , Esferoides Celulares/fisiologia , Transplante Heterólogo , Resultado do Tratamento , Cordão Umbilical/citologia , Cordão Umbilical/metabolismoRESUMO
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.
Assuntos
Nucleotídeo Cíclico Fosfodiesterase do Tipo 7/antagonistas & inibidores , Nucleotídeo Cíclico Fosfodiesterase do Tipo 7/metabolismo , Inibidores Enzimáticos/farmacologia , Hipocampo/metabolismo , Potenciação de Longa Duração/efeitos dos fármacos , Animais , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos C57BL , Plasticidade Neuronal/efeitos dos fármacosRESUMO
The development of catatonic reactions with rigid muscle tension due to stimulation of the skin at the scruff (catatonia-"pinch" test) and wax muscle plasticity (repeated pinch-induced catalepsy displayed on the parallel bars--BAR-test) was investigated in aggressive and submissive CBA/Lac male mice with repeated experiences of social victories (winners) or defeats (losers), accordingly. The expression of catatonic-like state in "pinch" test was significantly more in the losers after 20 daily agonistic confrontations in comparison with the winners. The catalepsy in the BAR-test was increased in animals with experience of agonistic confrontation in comparison with the controls, however expression of catalepsy reaction depended on kind and duration of agonistic interactions. The pronounced freezing predominated in the free behavior of the losers and, on the contrary, the winners demonstrated the abnormal undirected jumping. It was suggested that two contrast forms of catatonic syndrome accompanying by development of akinesia- or hiperkinesia-like states, are developed in the defeated and victorious (accordingly) mice of cataleptic CBA/Lac strain.