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.

Cerebral Expression of the Neuregulin-1 Gene NRG1 during Induced Spatial Memory Impairment and Its Reversal in Aging Mice.

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.

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.

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.