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We studied the effects of chronic intranasal administration of amyloidogenic fibrils of the proinflammatory protein S100A9 alone or in combination with glutamate antibodies on the expression of the neuregulin-1 gene (NRG1), a regulator of various physiological processes, in particular, regulation of neurogenesis and apoptosis, in the hippocampus, prefrontal cortex, and cerebellum of aging C57BL/6 mice under conditions of long-term memory disturbances. Under conditions of amnesia induced by S100A9 fibrils, pronounced (>90%) blockade of the expression of the NRG1 gene was found in all cerebral structures. Glutamate antibodies prevented/corrected disturbances in the cerebral expression of the NRG1 gene, thereby maintaining the activity of the NRG1/ErbB molecular signaling system, probably associated with the formation of spatial memory., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

We measured the level of natural antibodies (nAb) to glutamate and GABA reflecting the balance of excitation and inhibition systems and involved in the adaptation processes in athletes receiving normalized physical activity in the dynamics of training (figure skaters, football players, and people actively involved in sports). It was found that each subject has an individual immunological profile and its parameters change in accordance with the training load. The measured levels of nAbs to GABA and glutamate correlate the physical activity of a person. The surveyed football players were divided into 3 groups according to the results of the analysis. Subjects of the first group had reliably high immunological indices in comparison with the control and were at the peak of physical form; in the third group, low immunological indices relative to the control indicated exhaustion and fatigue. The indicators of the second group corresponded to normal and demonstrated the resource of adaptation to load. The developed method can be used for assessing person's readiness for physical activity., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Proinflammatory S100A9 protein is a promoter of inflammation-linked neurodegeneration and the Tnfrsf1A gene encodes the TNF receptor 1A that binds TNFα to function as a regulator of inflammation. We studied the effects of chronic intranasal administration of in vitro prepared S100A9 fibrils alone or in combination with anti-glutamate antibodies on the expression of the Tnfrsf1A gene in the hippocampus, prefrontal cortex, and cerebellum of aging C57BL/6 mice under conditions of impaired spatial memory. A differential cerebral pattern of Tnfrsf1A gene activity and its modification by S100A9 fibrillar structures were observed: inhibition of Tnfrsf1A gene expression in the hippocampus and cerebellum and its activation in the prefrontal cortex. Anti-glutamate antibodies normalized the expression of the Tnfrsf1A gene in the prefrontal cortex by affecting the TNF signaling pathway and preventing the development of inflammation., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

We studied the effect of single and repeated intranasal administration of antibodies to glutamate in experimental parkinsonian syndrome induced by injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to C57BL/6J mice. Intranasal administration of anti-glutamate antibodies to mice in parallel with administration of MPTP over 10 days alleviated parkinsonian symptoms (oligokinesia and rigidity). In the serum of mice injected with antibodies to glutamate and/or MPTP, the titers of autoantibodies to glutamate and dopamine were higher than in control animals receiving saline. Single intranasal administration of anti-glutamate antibodies to mice with established parkinsonian syndrome did not affect the severity of parkinsonian symptoms.

Intranasal administration of antibodies to glutamate in a dose of 250 μg/kg for two weeks facilitated spatial learning and memory formation in the Morris water maze in aging C57BL/6 mice. In animals treated with glutamate antibodies, the content of serotonin and dopamine metabolites 3-MT and HVA in the hippocampus decreased, but no changes in the metabolism of neurotransmitter acids were revealed. In the prefrontal cortex, dopamine level decreased and the content of its metabolite DOPAC increased; in parallel, an increase in excitatory and inhibitory amino acids (aspartic acid, glutamate, glycine, taurine, and GABA) was observed.

The survey included volunteer students of secondary and higher educational institutions. Two groups have been formed based on the results of clinical and laboratory studies. Group 1 comprised students occasionally using cannabinoids and amphetamines (risk group for psychoactive substances addiction) and group 2 included students who do not use drugs. The serum level of autoantibodies to norepinephrine, dopamine, and serotonin was reduced in the risk group.

The effects of intranasal pretreatment with antibodies against glutamate on focal penicillin-induced epileptic activity were studied by recording electrocorticogram in non-anesthetized freely moving male Wistar rats. Anticonvulsant effects of intranasal administration of anti-glutamate antibodies (300 μg/kg) 1 h before application of penicillin (30,000 U/ml) on the sensorimotor cortex was demonstrated: the latency of ictal discharges increased and their frequency decreased.

The dose-dependent effect of intranasal administration of antibodies to glutamate on acute generalized epileptic activity was studied in C57Bl/6 mice. It was shown that pretreatment with antibodies in doses of 100, 300, and 500 μg/kg 1 h before titration with convulsant pentylenetetrazole had anticonvulsant effects. This treatment was followed by an increase in the thresholds of clonic and tonic seizures with fatal outcome and lengthening of seizure latency. The most pronounced effect was observed in doses of 300 and 500 μg/kg. Comparison of the anticonvulsant effect of antibodies in active immunization with glutamate-BSA conjugate and systemic intraperitoneal administration of purified anti-glutamate antibodies revealed advantages of intranasal administration.

We studied the effects of intranasal administration of antiglutamate antibodies on the development of stress response and level of neurotransmitter amino acids and monoamines in brain structures of rats with different initial behavioral activity. The stress exposure was followed by significant changes in behavioral activity and concentration of neurotransmitters in rat hippocampus and hypothalamus. The changes in the level of neurotransmitter amino acids and monoamines were more pronounced in the hippocampus. Antiglutamate antibodies administered intranasally in a single dose of 250 μg/kg immediately after stress exposure prevented the development of the stress response and normalized the level of neurotransmitters in the brain structures of rats. The effect of antibodies was the most pronounced in behaviorally active rats.

Experiments on rats have showed that neurodegenerative damage to the brain induced by injection of a neurotoxic β-amyloid protein fragment β25-35into the basal giant cell nuclei of Meynert activated caspase-3 in the prefrontal cortex and hippocampus on day 3 after injury. Intranasal administration of antibodies to glutamate in a dose of 300 μ g/kg 1 h after damage reduced enzyme activity in these structures in a rat model of Alzheimer's disease.

Experiments on the model of bilateral photothrombosis in the prefrontal cortex showed that antibodies to glutamate administered intranasally 1 h after ischemic damage to the brain cortex led to a decrease in glutamate content in the hippocampus and prefrontal cortex and had no effect on aspartate concentration in these structures of the brain.

Experiments on rats showed that neurodegenerative brain damage caused by administration of neurotoxic fragment of β-amyloid protein Aβ25-35 in a dose of 2 μg into Meynert giant cell nucleus leads to long-term memory impairment in rats. Intranasal administration of antibodies to glutamate in a dose of 300 μg/kg 1 h after damage restores learning capacity of the experimental animals in the conditioned passive avoidance paradigm.

We studied the dose-dependent effect of antibodies to glutamate on the stress response in C57Bl/6 mice. The antibodies were administered immediately after stress exposure. Intranasal administration of antibodies to glutamate in doses of 150 and 250 μg/kg immediately after stress exposure was shown to reduce the stress response under conditions of combined restraint stress. This effect was most pronounced after treatment with antibodies in a dose of 250 μg/kg: we revealed a decrease in the number and severity of erosive and ulcerative lesions in the gastric mucosa, i.e. anti-glutamate antibodies have a protective effect.

Experiments were performed on rats with bilateral photothrombosis of vessels in the prefrontal cortex. Intranasal administration of antibodies to glutamate (1 h after ischemia of the brain cortex) improved retention of conditioned passive avoidance response, which was elicited before ischemic damage. The content of antibodies to glutamate in the serum of rats increased significantly on day 8 after bilateral photochemical thrombosis of vessels in the prefrontal cortex compared to that in the control.

We studied the effects of antibodies to glutamate and GABA administered intranasally 1 h before and immediately after stress on the development of stress response in C57Bl/6 mice. Antibodies to glutamate administered 1 h before stress prevented the development of the stress-reaction judging from behavioral parameters in the open field test and hyperalgesia test, while antibodies to GABA potentiated the severity of stress-induced behavioral disorders: total behavioral activity in the open field decreased significantly. When administered after stress, antibodies to glutamate did not reduce, but exacerbated stress reaction; antibodies to GABA also exhibited a stress-potentiating effect.

Increased production of autoantibodies to glutamate was found in blood plasma from patients with Alzheimer's dementia. The content of autoantibodies to glutamate in patients with early-onset Alzheimer's disease was much lower than in those with late-onset Alzheimer's disease (1.40+/-0.07 and 1.80+/-0.07 arb. units, p<0.001). The level of autoantibodies to glutamate in patients with mixed - Alzheimer's disease was 1.60+/-0.01 arb. units.

We studied the effect of antibodies to glutamate and GABA (active immunization with conjugates of glutamate--bovine serum albumin and GABA--bovine serum albumin) on the course of combined water-immersion stress in C57Bl/6 mice. Preimmunization of animals with the conjugate of glutamate--bovine serum albumin was accompanied by strong production of antibodies to glutamate, which reduced the majority of signs of the stress response. Antibodies to GABA had no effect on the development of stress.

Combined stress exposure of rats can lead to the formation of autoantibodies to neurotransmitters. Repeated stress is associated with the production of autoantibodies to serotonin, dopamine, norepinephrine, glutamate, and GABA. High emotional and behavioral reaction to stress is associated with intensive production of autoantibodies to serotonin, dopamine, norepinephrine, and glutamate.

The production and role of autoantibodies against neurotransmitters glutamate, gamma-aminobutyric acid, and norepinephrine were studied in rats with experimental neuropathic pain syndrome induced by sciatic nerve transection. Nerve transection in rats was followed by behavioral reaction of autotomy (self-mutilation of the operated limb), which often accompanies neuropathic pain syndrome. The development of neuropathic pain syndrome was accompanied by increased production of autoantibodies against glutamate, gamma-aminobutyric acid, and norepinephrine. A negative correlation was found between the amount of autoantibodies against neurotransmitters and severity of neuropathic pain syndrome. Our results suggest that antibodies against glutamate and norepinephrine exhibit protective activity.

We studied the effect of single intraperitoneal injection of antibodies against glutamate on acute generalized epileptiform activity induced by intravenous injection of pentylenetetrazole in kindled C57Bl/6 mice. We found that in animals at various stages of kindling, administration of antibodies against glutamate in a dose of 25 mg/kg 1.5 h before testing increases the threshold of clonic seizures and tonic phase of seizures with lethal outcome and latency of seizure development, i.e. produces an antiepileptic effect.

Experiments on C57Bl/6 mice showed that chronic epileptization of the brain (pharmacological pentylenetetrazole kindling) is accompanied by induction of autoantibodies against glutamate and GABA. Immunohistochemical similarity of antibodies against glutamate and GABA was demonstrated. Study on the model of pentylenetetrazole-induced acute generalized epileptiform activity showed high immunobiological specificity of intraperitoneally injected antibodies against GABA and glutamate: antiepileptic effect of antiglutamate antibodies and proepileptic effect of antibodies against GABA.

We studied the effect of single intraperitoneal treatment with antibodies to glutamate on pentylenetetrazole-induced acute generalized epileptiform activity in C57Bl/6 mice. The antiepileptic effect was observed 1.5 and 24 h after administration of antibodies to glutamate in doses of 10, 25, and 50 mg/kg. This treatment increased the thresholds of clonic seizures and tonic phase of seizures with lethal outcome.

We studied the effects of active immunization with glutamate-protein conjugates on behavioral reactions of C57Bl/6 and BALB/c mice in the open-field test and on animal anxiety in the tail suspension test. Antiglutamate antibodies produced different behavioral changes in mice of these strains.

Immunization of BALB/c mice with glutamate-BSA conjugate reduced anxiety and improved passive avoidance retention, while in C57Bl/6 mice immunization disturbed passive avoidance retention, but had no effect on anxiety. Interstrain differences in the shuttle box behavior were found between control animals.