Peculiarities of the Composition of Peripheral Immune Cells and Cytokine Profile in Brain Structures in Mutant DISC1-L100P Mice.

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.

Cytokine Content in the Hypothalamus and Hippocampus of C57Bl/6J Mice with Depressive-Like Behavior.

The content of pro- and anti-inflammatory cytokines in the hypothalamus, hippocampus, and blood serum of C57Bl/6J mice with depressive-like behavior induced by 20-day social stress was analyzed in 4 h after immune stimulation with LPS (250 µg/kg). These animals are characterized by a tendency to an increase in the blood content of IL-6 and a decrease in the level of IL-10. Changes in cytokine content in the brain of mice with depressive-like state developed under these conditions were observed only in the hippocampus: the levels of IL-1ß, IL-6, TNFα, and IL-10 increased and the content of IFNγ decreased in comparison the corresponding parameters in the controls (not exposed to social stress) and aggressive animals. No changes in the levels of IL-2, IL-4, and IL-17 were revealed in the hypothalamus and hippocampus.

Cytokine Production by Splenic Cells in C57BL/6J Mice with Depression-Like Behavior Depends on the Duration of Social Stress.

We studied the influence of depression-like behavior developed in C57BL/6J mice under conditions of social stress of different duration on cytokine production by splenic cells. Imbalance of the pro- and anti-inflammatory cytokines was detected at the early stage of depression-like behavior (10-day experience of defeats): increased production of proinflammatory IL-2 and IL-6 cytokines along with a decrease in anti-inflammatory IL-10 level; the levels of IL-1ß, TNFα, IFNγ, and IL-4 remained unaffected. At later terms (20 days of confrontations), we revealed more pronounced changes in spontaneous production of proinflammatory cytokines that were not detected after shorter social stress. These findings suggest that cytokine profile depends on duration of social stress. Possible mechanisms of cytokine production during formation of depression-like state are discussed.

[T-lymphocyte subpopulations and immune response in mice of the ASC strain with depressive-like behaviour].

Analysis of the content of CD16/32+, CD4+ and CD8+ -cells was perfomed in the peripheral blood and spleen ofmice of the ASC strain with high predisposition to depressive-like state in comparison with mice of parent CBA strain having no depressive behaviour. In both cases, ASC mice showed a decrease in the percentage of CD16/32+ and CD4+-cells along with an increase CD8 cells and lowering of immunoreactivity index (CD4+/CD8+). Changes in cellular subpopulations found in intact ASC mice was accompanied with animals' low capacity to respond to T-dependent antigen: sheep red blood cells at the dose of 5 x 10(8). In contrast to CBA mice the percentage and absolute number of IgM-antibody-forming cells were significantly decreased in the spleen of ASC mice on the 4th and 5th days after immunization as well as the numbers of IgG-antibody-forming cells on the 6th day of the immune response. Possible mechanisms underlying the immune reactivity inhibition under depressive-like state are discussed.

[Changes in the number of CD4+ T-helpers in the bone marrow of aggressive mice of C57BL/6J and CBA strains]. / Izmenenie chisla CD4+ T-khelperov v kostnom mozge u aggressivnykh myshei linii C57BL/6J i CBA.

Aggressive behaviour led to immunostimulation with a subsequent rise in the number of T-helpers in C57B1 and CBA mice. The number of CD4+ T-helpers in their bone marrow correlated with duration of successive experience of victories. The effect of such a behaviour on immunity seems to be due to an activation of the dopaminergic system.

[Increase of the number of bone marrow T-suppressor cells under inhibition of immunogenesis during changes of the activity of the neuromediator system]. / Povyshenie chisla T-supressorov kostnogo mozga v usloviiakh ugneteniia immunogeneza pri izmenenii aktivnosti neiromediatornykh sistem.

Increase of serotoninergic system activity and blockade of dopaminergic system activity led to the change of T- and B-lymphocyte distribution in immunocompetent organs of non-immunized animals. Increase of suppressor cel number with Lyt2.2 phenotype was found in bone marrow of C57Bl/6 mice under activation of serotoninergic system (blockade of serotonin reuptake by sertraline) as well as under blockade of dopaminergic system by administration of dopamine autoreceptor agonist--3-PPP. Role of bone marrow in neuro-immunomodulation is discussed.

[Level of serotonin and 5-hydroxyindoleacetic acid in the brain and immunocompetent organs after immunization]. / Uroven' serotonina i 5-oksiindoluksusnoi kisloty v mozge i immunokompetentnykh organakh posle immunizatsii.

Twenty minutes after immunization the activation of the serotoninergic system was observed. High level of serotonin metabolism was retained for 24 h after immunization. Change of serotonin level in immunocompetent organs and adrenals took place later than in the brain.

[Changes in the level of dopamine and its metabolites in brain structures and immunocompetent organs in the formation of immune response]. / Izmenenie urovnia dopamina i ego metabolitov v strukturakh mozga i immunokompetentnykh organakh pri formirovanii immunnogo otveta.

By the method of liquid chromatography with electrochemical detection dopamine level increase was shown within 2 min after immunization of rats with sheep red blood cells in n. caudatus. In 20 min after the immune response the acceleration of dopamine metabolism was observed in nuclei A9, A10, A11, accumbens, in amygdala, hypothalamus and hippocampus. In immunocompetent organs dopamine level was changed in 24 h after the immunization.