Effect of Glutamate Antibody F(ab)2 Fragments on Memory Changes in Aged C57BL/6 Mice.

Intranasal administration of F(ab)2 fragments of anti-glutamate antibodies to 12-month-old C57BL/6 mice improves passive avoidance conditioning and have no effect on horizontal and vertical locomotor activity in the open-field test. In contrast to full-length antibodies to glutamate, their F(ab)2 fragments significantly increase the number of animals developed a conditioned passive avoidance reflex.

Correlation of Antibodies to Neurotransmitters in the Sera of Women with Alcohol Dependence and Depressive Disorders.

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.

Delayed Behavioral and Neurochemical Effects of Anti-Glutamate Antibodies in Aging C57BL/6 Mice.

We analyzed delayed effect of intranasal administration of anti-glutamate antibodies on mnestic function and tissue concentrations of neurotransmitters in the hippocampus and prefrontal cortex in aging C57BL/6 mice. It was found that after 14-day administration of anti-glutamate antibodies, improvement of the passive avoidance conditioning persisted for 7 days after the treatment was discontinued. In 7 days after discontinuation of treatment, increased content of dopamine and its metabolites as well as aspartic acid and taurine was observed in the hippocampus of mice treated with anti-glutamate antibodies. In the prefrontal cortex, administration of anti-glutamate antibodies had no effect on the levels of neurotransmitters, but increased the concentration of glutamate.

Effect of Anti-Glutamate Antibodies in Modeled Parkinsonian Syndrome.

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.

Antibodies to Glutamate Facilitate Spatial Memory Formation in the Morris Water Maze in Aging C57BL/6 mice.

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.

Effect of Antibodies to Glutamate on Age-Related Memory Changes in C57Bl/6 Mice.

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.

Effect of Anti-Norepinephrine Antibodies on the Development of Neuropathic Pain.

The study focuses on induction of autoantibodies directed against neurotransmitter norepinephrine during neuropathic pain syndrome and on the effect of immunization with norepinephrine-protein conjugated antigen on the development of this syndrome. The formation of anti-norepinephrine antibodies aggravated and prolonged neuropathic pain.

Antibodies to Glutamate Reversed the Amnesic Effects of Proinflammatory S100A9 Protein Fibrils in Aged C57Bl/6 Mice.

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.

[Effect of intranasally administered glutamate antibodies on the content of excitatory and inhibitory amino acids in the rat`s hippocampus and hypothalamus at the combined stress exposure].

Objective. We studied the effect of glutamate antibodies by intranasal administration on the development of stress reactions and aspartate, glycine and taurine content in the brain structures of rats with different initial behavioral activity (active and passive). Methods. Stress caused by placing the animals in the living cell with water (21°Ð¡) covered with a grid for 30 min. Glutamate antibodies in a dose of 250 mg/kg in a volume of 10 mkl were administered intranasally to the experimental group of rats immediately after the stress. After 1 h after stress exposure and antibodies administration in all rats was investigated motor activity in the test of the «open field¼. Amino acids aspartate, glycine and taurine in the brain structures (hippocampus and hypothalamus) were determined by HPLC with fluorescence detection. Results. Combined water-immersion stress caused significant changes in the behavioral activity of rats in the «open field¼, but a more pronounced decline in the total index were observed in the behaviorally passive group of rats. The stress was accompanied by a change in the content of neurotransmitter amino acids (glycine and taurine) in the hippocampus. The most significant changes in the levels of glycine (decrease) and taurine (an increase) was observed in the hippocampus behaviorally active rats. Glutamate antibodies at a dose of 250 mg/kg administered intranasally immediately after stress exposure prevents the development of behavioral stress reactions and contributed to an increase in the hippocampus the content of glycine and taurine, related to stress-limiting systems. Conclusions. The glutamate antibodies under stress act as endogenous bioregulators and prevent the development of stress reactions.

[Autoantibodies to glutamate, GABA and their receptors in epilepsy].

This review discusses the pathogenic role of autoantibodies (autoAB) to excitatory and inhibitory neurotransmitters glutamate, GABA and their receptors in the pathogenesis of epilepsy. The data of clinical and experimental studies show that glutamate AMPA and NMDA- receptors autoAB and GABA receptors autoAB in high titers are highly pathogenic, causing a significant decrease of the density of the receptors and contribute the neuronal death. Discusses the results of experimental data about of the anticonvulsant action of glutamate antibodies (AT) and opposite proconvulsant effect of GABA antibodies in different models of epileptic activity.

[Autoantibodies to glutamate and GABA in opiate addiction].

Blood serum from 129 patients with opium addiction at different stages of the disease and 63 donors (control group) was examined for the presence of autoantibodies to the exciting and inhibitory amino acids glutamate and GABA. It was shown enhanced production of autoantibodies to glutamate and GABA. Dependence of the level and frequency of detec- tion of autoantibodies to glutamate and GABA on the stage of the disease was revealed.

Stress-sensitive organs and blood corticosterone after immobilization of active and passive rats immunized with glutamate-bovine serum albumin conjugate.

We studied stress-induced organ and hormonal responses in behaviorally active and passive rats against the background of immunization with glutamate-BSA conjugate. The relative weight of the adrenal glands after immobilization was lower in rats immunized with the conjugate in comparison with non-immunized animals. The weight of the adrenal glands in behaviorally active rats decreased in parallel with the decrease in blood corticosterone. In behaviorally active and passive rats immunized with the conjugate, ulcer formation in the stomach was slightly intensified after immobilization. It was hypothesized that immunization with glutamate-BSA conjugate suppresses activity of the hypothalamic-pituitary-adrenal feedback mechanism underlying the production of glucocorticoid hormones, which is manifested in slightly increased ulceration due to attenuation of the gastroprotective action of corticosterone under stress.

Ratio of antibodies to neurotransmitters in the serum of students, occasional drug users.

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.

[Neuroimmunological aspects of the pathogenesis of epilepsy].

The review is devoted to the analysis of neuroimmunological aspects of the pathogenesis of epilepsy. Discuss the pathogenetic role of proinflammatory cytokines, antibodies to antigens of the nervous tissue and neurotransmitters, such as dopamine, serotonin, glutamate and GABA in the pathogenesis of epilepsy. The focus of the review is given to clinical research, devoted to the interrelation of the severity of the disease and changes of immunological indices. Disorders of the immune system are most pronounced in drug-resistant forms of epilepsy. Describes the clinical and experimental research, which shows that the use of antiepileptic drugs improves immunity. The use of immunotherapy in combination with anti-epileptics drugs leads to positive results. Thus, the analysis of the immune status of patients with epilepsy can serve as an important criterion for determining the severity of the disease and the appointment of adequate treatment. The authors analyze their own data of anticonvulsant activity of antibodies to glutamate and opposite proconvulsant effect of antibodies to GABA.

[The role of antibodies to neurotransmitters of antinociceptive system in mechanisms of neuropathic pain].

The present investigation was undertaken in order to study the role of the antibodies to neurotransmitters of antinociceptive system in pathogenesis of neuropathic pain on models of neuropathic pain. It was shown that the development of experimental neuropathic pain syndrome is accompanied with induction of autoantibodies to CABA, serotonin, noradrenalin and dopamine. It was established that the antibodies to neurotransmitters of antinociceptive system have a pronociceptive effect.

Effects of antibodies to glutamate on focal penicillin-induced epileptic activity.

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.

Elevation of seizure threshold after intranasal administration of anti-glutamate antibodies to C57BL/6 mice.

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.

Effects of antiglutamate antibodies on the development of stress response and neurotransmitter content in the hippocampus and hypothalamus of rats with different behavioral activity.

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.

[Antibodies to neurotransmitters as possible neuroimmune risk markers of formation dependence to psychoactive substances].

In the sera of patients with opioid addiction has been found elevated levels of autoantibodies to the neurotransmitters dopamine, norepinephrine and serotonin in comparison with a control group of healthy people of the same age. In the group of patients with acute withdrawal was showed a reduction of antibody to dopamine, noradrenaline and serotonin in the blood serum when compared with patients in the period of postabstinent disorders. In the group of patients with risk for the formation of substance dependence in serum was observed decrease in autoantibodies to dopamine and norepinephrine compared with the control group.

[Influence of antibodies to the glutamate on convulsive reaction to mice C57Bl/6 in term of chronic epileptogenesis].

It was shown that the preliminary single i.p. injection of antibodies (AB) to glutamate (GLU) 1,5 hours prior to the first injection pentylenetetrazole (prior to the beginning of kindling) did not have an effect on latency period of appearance and the severity of convulsive reactions in the mice of C57Bl/6. The administrations of AB to GLU at the different stages of kindling animals with different severity of seizures did not have an effect on their severity. Thus, AB to GLU did not posses antiepileptic effect. However, AB to GLU posses anticonvulsive action on the acute seizures reaction, inducing an increase in the thresholds of clonic seizures and tonic phase seizures with lethal outcome as well as an extended latency period of occurrance these seizures in mice with enhanced kindling-producing convulsive readiness of the brain. This effect was revealed at the different stages of kindling in animals with the severity of seizures 2-3 and 4-5 marks. Possible to assume, that the mechanisms of chronic epileptogenesis (in this case, in the form kindling-dependent enhanced convulsive readiness of the brain) and those of the acute convulsive reaction are not similar.