IntroductionExistence of integration, mutual relations of nervous and immune systems, which cellular elements are characterized by expressed phenotype and functional similarity, means the possibility of immune cells participation in the regulation of higher nervous activity.ObjectivesPreviously, we demonstrated the possibility of targeted regulation of animal's behavior by the transplantation of immune cells with definite functional characteristics. Based on the our previous research results in the present study, we investigated the modulating effect of the immune cells, treated in vitro with chlorpromazine on the nervous and immune systems functional activity in aggressive mice.Methods(CBA × C57Bl/6) F1 aggressive mice, exposed to 10-days chronic social stress, were undergoing the transplantation of immune cells in vitro treated with chlorpromazine. Animal's behavioral parameters, cytokines synthesis in the brain and immune cells before and after transplantation were estimated.ResultsIt was shown that aggression is associated with the increased production of spleen T-helper 1 cell-derived cytokines IL-2 and IFNγ, as well as decreased TNFα production by the spleen mononuclear phagocyte cells. These alterations were more pronounced following mitogen stimulation. Spleen cells, obtaining from aggressive mice, were treated in vitro with chlorpromazine and then injected intravenously into syngeneic aggressive recipients. The cell's transplantation led to the reduction of the recipient's motor activity in the “open field” and Porsolt swimming tests and normalized cytokines synthesis in the brain and immune cells.ConclusionResearch results demonstrated the neuroleptic effect in aggressive mice, obtained by the transplantation of immune cells treated in vitro with chlorpromazine.Disclosure of interestThe authors have not supplied their declaration of competing interest.

The purpose of this work was to study the effect of turmeric extract on behavior indicators, the severity of the cellular immune response in animals in a state of experimental alcoholism. Experimental models: mouse males (CBAxC57Bl/6)F1 three months of age (n = 60). Alcohol dependence in experimental animals was formed by the method of 6-month soldering with a 10% ethanol solution. In the control groups, the animals received per os water or 10% ethanol solution, in the experimental group - an extract of turmeric powder in a solution of ethanol. Mice behavior was assessed in the “open field” test. The severity of the cellular immune response to sheep erythrocytes was assessed by the intensity of the development of a delayed-type hypersensitivity reaction.It was found that the use of turmeric extract against the background of taking ethanol solution in animals with experimental alcoholism leads to the stimulation of behavior and the increase of the cellular immune response to the level characteristic of healthy animals of the corresponding age.Results indicates the protective effect of turmeric on a number of parameters of the functional activity of the nervous and immune systems during chronic ethanol intoxication.

IntroductionOriginal compound ortho-fluorobenzonal, a barbiturate derivative, is shown to reveal strong anticonvulsant activity by means increasing GABA-mediation. Disturbance of GABA(A) -receptors functions play an essential role in both alcoholism and epilepsy pathogenesis.Objectives Taking into account the presence of GABA(A)-receptors on the lymphocytes surface and involvement of immune system in alcoholism pathogenesis, we investigated ortho-fluorobenzonal effects on the immune and nervous systems functional activities in mice with chronic alcohol exposure to find new perspective pharmacological substances in the treatment of alcoholism.Methods(CBAxC57Bl/6) F1 male mice with 6-month 10% ethanol exposure were undergoing intragastric administration of original compound ortho-fluorobenzonal for 10 days. Animal’s alcohol consumption, behavior and immune parameters were estimated.ResultsIt was found that ethanol daily consumption decreased sharply starting from 2 days of ortho-fluorobenzonal administration and led to the cessation of ethanol consumption by the 4 day in mice with chronic alcohol exposure. Pronounced changes in motor and exploratory activities in “open field” test was registered in long-term alcoholized mice after 10- day course ortho-fluorobenzonal administration. The above behavioral changes were recorded against the brain cytokines synthesis modulation. We have shown also the modulation by ortho-fluorobenzonal of immune system functional activity, in particular, significant cellular and humoral immune response stimulation, estimated by the relative number of antibody forming cells and reaction of delayed-type hypersensitivity respectively.ConclusionsOriginal compound ortho-fluorobenzonal has a positive neuroimmunomodulation effect that manifests itself in the correction of iimmune and behavior disorders caused by the chronic ethanol exposure, therefore, this compound is promising in the therapy of alcoholismDisclosureNo significant relationships.

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ObjectiveViolation of the functional activity of the nervous and immune systems is an essential link in the pathogenesis of chronic alcohol dependence. The search for new psychopharmacological agents whose action is directed to correction of neuroimmune interaction opens new perspectives for the treatment of alcohol dependence.Methods(CBAxC57Bl/6) F1 mice with active and passive behavioral types in a state of chronic alcohol dependence owing to 6 month 10% ethanol exposure were undergoing intragastric administration of original anticonvulsant meta-chloro-benzhydryl-urea. Animal's behavioral and immune parameters, brain cytokines synthesis before and after anticonvulsant receiving were estimated.ResultsIn the formation of experimental alcohol dependence in animals the most pronounced changes in motor and exploratory activities in open field test, brain cytokines synthesis and suppression of immune response were registered in mice with passive type of behavior. Daily consumption of ethanol solution in mice with chronic alcohol dependence decreased sharply starting from 2 days of anticonvulsant administration and led to the cessation of ethanol consumption by the 5 day. After anticonvulsant administration for 10 days behavioral parameters in mice were comparable with those in the control group of healthy animals. It also restored brain cytokines synthesis and significant stimulated humoral immune response, estimated by the relative number of antibody-forming spleen cells.ConclusionBehavior and immune changes following chronic ethanol exposure depended on the behavior status of animals; administration of the original anticonvulsant meta-chloro-benzhydryl-urea may correct both immune and behavior disorders in mice with chronic alcohol dependence, so it has promise in the treatment of alcoholism.Disclosure of interestThe authors have not supplied their declaration of competing interest.

In the current report, the effect of bioactive compounds of the M2 macrophage secretome on transcription of hippocampal genes in mice with a depression-like condition caused by social stress has been investigated. Surgically resected hippocampus was used for mRNA isolation with following RNA sequencing procedures. Comparative analysis of transcriptomes from the control depressive mice treated with physiological saline solution and mice after intranasal administration of M2 macrophages-conditioned medium revealed that remission of the depressive-like state is associated with a significant up- and downregulation of a number of genes, which were found to participate in restoration/regulation of ATP/Adenosine balance. Among the events associated with positive changes in behavioral pattern of depressive mice, the switch of microglial environment from a pro-inflammatory phenotype to an anti-inflammatory one, and subsequent restoration of compromised cannabinoid and glutamatergic transmitter pathways has been predicted.

IntroductionIn the scientific world widely discussed phenomenon of “cytokine-induced depression”. Macrophages have high plasticity and are able to control the inflammatory response; in particular, anti-inflammatory type-2 macrophages have a pronounced potential due to complex soluble factors production.ObjectivesWe have developed an original method for the type-2 macrophages generation; the resulting macrophages are characterized by the high level of a whole range of neurotrophic, neuroprotective, proangiogenic and anti-inflammatory factors production. The aim of the study was to investigate effects of human type-2 macrophages soluble products on behavioral phenotype and brain cytokines synthesis in depressive-like animals.MethodsType-2 macrophages were generated by culturing an adherent fraction of mononuclear cells with 50 ng/ml recombinant human GM-CSF in serum deprivation conditions for 7 days. (CBA x C57Bl/6)F1 depressive-like male mice, developed under the long-term social stress, were undergoing the human type-2 macrophages conditioned medium intranasal administration (60 ml twice daily for one animal) for 6 days. Mice behavioral phenotyping was carried out using an automatic registration system (Noldus Information Technology). Cytokines were determined by ELISA.ResultsDepressive-like mice behavioral phenotyping after type-2 macrophages conditioned medium administration revealed anhedonia decrease, motor activity stimulation in the open field and forced swimming tests, anxiety reduction in elevated plus maze. Behavioral changes were recorded against the pro-inflammatory cytokines (TNF-α, IL-1β, IL- 6, INFγ) decrease in striatum and hippocampus, as well as anti-inflammatory IL- 10 increase in hippocampus and hypothalamus.ConclusionsResults demonstrated the effectiveness of human type-2 macrophages biologically active soluble products in relation to the stress-induced depressive-like behavior editingDisclosureNo significant relationships.

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