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Comparative analysis of blood sera from women with alcohol dependence and depressive disorders or from conditionally healthy women revealed reduced level of antibodies to dopamine, norepinephrine, serotonin, glutamate, and GABA in blood serum in women with dysthymic disorder and a depressive episode and their increased content in women with alcohol dependence in combination with depressive disorders.

Intranasal administration of antibodies to glutamate at dose of 250 μg/kg for two weeks facilitated spatial learning and memory formation in the Morris water maze in aging C57Bl/6 mice. Concurrently, in the animals treated with glutamate antibodies, there was a decrease in serotonin level, no change in dopamine but a reduction in 3-MT and HVA metabolite concentrations in the hippocampus. In the prefrontal cortex, a decrease in dopamine level occurred along with a simultaneous increase in the content of its metabolite, DOPAC, as well as an increase in excitatory and inhibitory amino acid neurotransmitters: aspartic acid, glutamate, glycine, taurine and GABA. It was concluded that Abs-Glu facilitated spatial learning and memory formation through a remodeling of the hippocampal and prefrontal cortical neurochemical system in aging C57Bl/6 mice.

The aim of the study is to search for biomarkers of risk and prevention of the formation of alcohol dependence on the background of depression. Antibodies are evaluated for a number of neurotransmitters, the information content of which is confirmed by preliminary studies. Materials and methods. Autoantibodies to dopamine, norepinephrine, 5-hydroxytryptamine, glutamate, gamma-aminobutyric acid were determined by ELISA in 60 controls and patients with depression and alcohol use disorder (AUD). Results. The level of antibodies to all studied neurotransmitters decreases with depression, especially complicated by alcoholism. An exception is the level of antibodies to serotonin, which increases with AUD and depression combined with AUD. Conclusion. It is assumed that this type of reaction may be a biomarker of the risk of alcoholism in depression.

Chronic intranasal administration of antibodies to glutamate to aging C57Bl/6 mice improved passive avoidance conditioning, had no effect on horizontal and vertical locomotor activity, but slowed locomotion in the open-field test. Administration of antibodies to glutamate increased the content of dopamine and its metabolites in mouse hippocampus, but had no effect on the metabolism of neurotransmitter amino acids. In the frontal cortex, antibodies to glutamate did not affect neurotransmitter metabolism, but increased the level of both excitatory and inhibitory amino acids without changing their ratio.

Amyloid formation and neuroinflammation are major features of Alzheimer's disease pathology. Proinflammatory mediator S100A9 was shown to act as a link between the amyloid and neuroinflammatory cascades in Alzheimer's disease, leading together with Aβ to plaque formation, neuronal loss and memory impairment. In order to examine if S100A9 alone in its native and amyloid states can induce neuronal stress and memory impairment, we have administered S100A9 species intranasally to aged mice. Single and sequential immunohistochemistry and passive avoidance behavioral test were conducted to evaluate the consequences. Administered S100A9 species induced widespread cellular stress responses in cerebral structures, including frontal lobe, hippocampus and cerebellum. These were manifested by increased levels of S100A9, Bax, and to a lesser extent activated caspase-3 immunopositive cells. Upon administration of S100A9 fibrils, the amyloid oligomerization was observed in the brain tissues, which can further exacerbate cellular stress. The cellular stress responses correlated with significantly increased training and decreased retention latencies measured in the passive avoidance test for the S100A9 treated animal groups. Remarkably, the effect size in the behavioral tests was moderate already in the group treated with native S100A9, while the effect sizes were large in the groups administered S100A9 amyloid oligomers or fibrils. The findings demonstrate the brain susceptibility to neurotoxic damage of S100A9 species leading to behavioral and memory impairments. Intranasal administration of S100A9 species proved to be an effective method to study amyloid induced brain dysfunctions, and S100A9 itself may be postulated as a target to allay early stage neurodegenerative and neuroinflammatory processes.

Alpha-synuclein (α-syn) toxic aggregates delivered by the nasal vector have been shown to modify the neurochemistry of dopamine (DA) which is associated with parkinsonian-like motor symptoms. The aim was therefore to study the intranasal effects of α-syn oligomers, fibrils or their combination on the motor behavior of aged mice in relation to possible noradrenergic and serotonergic correlates. In vitro generated α-syn oligomers and fibrils were verified using atomic force microscopy and the thioflavin T binding assay. Levels of noradrenaline (NA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were detected using HPLC with electrochemical detection in the substantia nigra (SN) and striatum. The oligomers or fibrils administered alone or in a 50:50 combination (total dose of 0.48 mg/kg) were given intranasally for 14 days and "open-field" behaviour was tested on days 0, 15 and 28 of the protocol, at which time brain structures were sampled. Behavioral deficits at the end of the 14-day dosing regime and on day 28 (i.e. 14 days after treatment completion) induced hypokinesia and immobility whilst the aggregate combination additionally produced rigidity. The α-Syn oligomer/fibril mixture also instigated PD-like motor symptoms which correlated heterochronically with elevated NA levels in the striatum but then later in the SN while intranasal fibrils alone augmented 5-HT and 5-HIAA nigral concentrations throughout the protocol. In contrast, α-syn oligomers displayed a delayed serotonin upsurge in the SN. Neurodegenerative and/or actions on neurotransmitter transporters (such as NET, SERT and VMAT2) are discussed as being implicated in these α-syn amyloid induced neurochemical and motoric disturbances.

Alzheimer’s disease (AD) involves dementia conceivably arising from integrated inflammatory processes, amyloidogenesis, and neuronal apoptosis. Glutamate can also cause neuronal death via excitotoxicity, and this is similarly implicated in some neurological diseases. The aim was to examine treatment with in vitro generated proinflammatory protein S100A9 aggregate species alone or with glutamate antibodies (Glu-Abs) on Morris water maze (MWM) spatial learning and memory performance in 12 month old mice. Amino acid and monoamine cerebral neurotransmitter metabolic changes were concurrently monitored. Initially, S100A9 fibrils were morphologically verified by atomic force microscopy and Thioflavin T assay. They were then administered intranasally alone or with Glu-Abs for 14 days followed by a 5 day MWM protocol before hippocampal and prefrontal cortical neurochemical analysis. S100A9 aggregates evoked spatial amnesia which correlated with disrupted glutamate and dopaminergic neurochemistry. Hippocampal glutamate release, elevation of DOPAC and HVA, as well as DOPAC/DA and HVA/DA ratios were subsequently reduced by Glu-Abs which simultaneously prevented the spatial memory deficit. The present outcomes emphasized the pathogenic nature of S100A9 fibrillar aggregates in causing spatial memory amnesia associated with enhanced hippocampal glutamate release and DA-ergic disruption in the aging brain. This finding might be exploited during dementia management through a neuroprotective strategy.

Parkinson's disease (PD) is a neurodegenerative disorder in which both alpha-synuclein (α-syn) and dopamine (DA) have a critical role. Our previous studies instigated a novel PD model based on nasal inoculation with α-syn aggregates which expressed parkinsonian-like behavioral and immunological features. The current study in mice substantiated the robustness of the amyloid nasal vector model by examining behavioral consequences with respect to DA-ergic neurochemical corollaries. In vitro generated α-syn oligomers and fibrils were characterized using atomic force microscopy and the thioflavin T binding assay. These toxic oligomers or fibrils administered alone (0.48 mg/kg) or their 50:50 combination (total dose of 0.48 mg/kg) were given intranasally for 14 days and "open-field" behavior was tested on days 0, 15 and 28 of the protocol. Behavioral deficits at the end of the 14-day dosing regime and on day 28 (i.e., 14 days after treatment completion) induced rigidity, hypokinesia and immobility. This was accompanied by elevated nigral but not striatal DA, DOPAC and HVA concentrations in response to dual administration of α-syn oligomers plus fibrils but not the oligomers by themselves. α-Syn fibrils intensified not only the hypokinesia and immobility 14 days post treatment, but also reduced vertical rearing and enhanced DA levels in the substantia nigra. Only nigral DA turnover (DOPAC/DA but not HVA/DA ratio) was augmented in response to fibril treatment but there were no changes in the striatum. Compilation of these novel behavioral and neurochemical findings substantiate the validity of the α-syn nasal vector model for investigating parkinsonian-like symptoms.

Introduction. With the transport links development there is rather important issue respiratory viral infections spread, especially influenza. The only method controlling influenza is vaccination. Search and development effective and safe vaccines is important. Material and methods. In base SO "Mechnikov Institute Microbiology and Immunology National Ukrainian Academy Medical Sciences" in the scientific theme "Developing new approaches to creating viral vaccines and study specific activity depending of type and degree component`s modification" was created several experimental influenza vaccine with subsequent component`s modification for selecting the most optimal pattern of safety and immunogenicity. In assessing the influenza vaccine safety is using a few criteria, including, reactivity, as measured by the frequency of local and systemic adverse (negative) effects, which due to its introduction, and for lipid content drugs, ability to influence oxidation processes. At present study phase was determined: a) systemic reaction and local reaction of delayed-type hypersensitivity (foot pad swelling assay);b) lipids and proteins peroxidation processes after administration officinal and experimental vaccines (content protein’s carbonyl groups, lipid’s hydroperoxides, activity of glutathione-peroxidase).Study objects were trivalent seasonal influenza vaccine, "Vaxigrip" (Sanofi Pasteur, S.A., France), "Inflexal V" (Biotech Ltd. Berne, Switzerland) and experimental vaccine samples. Highest immunogenicity vaccines had undergone improvements and modifications using adjuvant systems and acylation influenza proteins. Liposomes 2 – the experimental influenza vaccine with a liposome negative charge and antigenic composition like split vaccines "Vaksihryp". Liposomes 2.1 - the adjuvantexperimental influenza vaccine with modifications liposomal components (etoniy and chlorophyllipt molecules embedded in liposomal membrane). Liposomes 2.2 - the adjuvant experimental influenza vaccine further modification through acylation antigenic component.Results and discussion. Among the vaccines with the antigenic component modification and addition of adjuvants, the highest production of specific influenza antibodies was observed after administration liposomes №2.2 sample, which was made on the basis of antigen Vaxigrip with negatively charged liposomal formulation, the addition of adjuvants and modification antigenic composition, the second ranked liposomes №2.1, without antigenic modification. The study identified regarding the frequency of local reactions, assessed by visual observations, among experimental animals in injection site after legalized vaccines or newly samples weren`t characterized by the formation of swelling, hardening of tissue hyperemia or painful local reactions throughout the observation time.Experimental mice also haven`t fever for the 5 days after manipulation, which is the main criterion of systemic adverse reactions after they administered vaccine preparations. Also after use of experimental drugs and drug comparison, subjective, wasn`t happened abnormalities in general condition animals, including a decrease in appetite, digestive disorders, changes in activity and more. These observations, however, do not allow to conclude the complete safety newly created experimental vaccine and require additional evaluation tests. As base component for building experimental liposomal vaccine used the fosfatydilholin (FH).FH is a substrate for activation lipid peroxidation. Lecithin liposomes, that are liposomal vaccine structural and functional components, are exposed to a variety number of physical and chemical factors. One of biochemical events, that happen to them, are lipid peroxidation, accompanied by free radicals appearance in the system and, ultimately, causes phospholipid bi-layer membranes degradation by a violation of their permeability and lysis. In this regard, system safety control and liposomal drug efficacy should include the definition the content lipid peroxidation products. Conclusion.Thus, experimental samples influenza liposomal vaccine (without modification and with its for liposomal and antigenic components) haven`t found increased levels primary products lipid peroxidation – lipid hydro peroxides and protein oxidation products – carbonyl protein and haven`t significant effects inhibition anti-oxidant enzymes in rat`s serum.More results the study stage the safety most effective vaccine samples will be present in the text.

Chronic intranasal administration of fibrillar structures of proinflammatory S100A9 protein impaired passive avoidance learning in old C57Bl/6 mice. Combined treatment with S100A9 fibrils and antibodies to glutamate was followed by an increase in horizontal locomotor activity of animals in the open-field test and did not disturb spatial memory.

Leukocyte count decreased, relative content of neutrophils and monocytes increased, and their phagocytic activity was suppressed in rats with 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine-induced depressive syndrome at the stage of acute behavioral depression. The severity of behavioral depression inversely correlated with changes in the absolute neutrophil and monocyte counts.

Changes in humoral and cell-mediated immunity are studied in rats with 1-methyl-4-phenyl-1,2,3,6—tetrahydropyridine (MPTP)-induced depressive syndrome. A decrease in the lymphocyte count and in absolute and relative T cell counts and absolute B cell counts in peripheral blood and an increase in serum concentration of circulating immune complexes (CIC) are demonstrated. Serum CIC content increases, while the relative count of peripheral blood T cells remains decreased two weeks after discontinuation of MPTP and normalization of rats' behavior. Serum CIC content decreases and T cell count normalizes one month after discontinuation of MPTP.

The frequency of sister chromatid exchanges in rabbit peripheral blood lymphocytes was estimated after three intravenous injections of thiophosphamide in doses of 0.5 and 2 mg/kg body weight at 2-week intervals. It is demonstrated that 24 h after the first injection the frequency is significantly higher than after subsequent injections.