Antibodies to Glutamate Facilitate Spatial Memory Formation in the Morris Water Maze in Aging C57BL/6 mice
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Bulletin of Experimental Biology and Medicine, Vol. 169, No. 1, May, 2020
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GENERAL PATHOLOGY AND PATHOPHYSIOLOGY Antibodies to Glutamate Facilitate Spatial Memory Formation in the Morris Water Maze in Aging C57BL/6 mice T. V. Davydova1, M. A. Gruden2, V. S. Kudrin3, V. B. Narkevich3, L. A. Vetrile1, I. A. Zakharova1, and R. D. E. Sewell4
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 169, No. 1, pp. 8-12, January, 2020 Original article submitted July 11, 2019 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. Key Words: aging; memory; antibodies to glutamate; neurotransmitters According to current views, aging is a physiological process accompanied by homeostasis disturbances and progressive age-related destabilization of vital functions. Aging is associated with cognitive deficits, in particular, impairment of memory and learning [11]. In this context, the search for new approaches to the prevention and correction of age-related changes in short- and long-term memory, as well as understanding processes underlying amnesia is the focus of medical research. Immunological approach to amelioration of cognitive impairment during aging, in particular, the use of antibodies to endogenous substances involved in molecular mechanisms of memory formation, is undoubtedly relevant. In previous studies, we demonstrated that chronic intranasal administration of anti-glutamate antibodies (Abs-Glu) to 12-month-old C57BL/6 mice (250 μg/kg) improved passive avoidance conditioning. Moreover, intranasal Abs-Glu did not afResearch Institute of General Pathology and Pathophysiology; 2P. K. Anokhin Research Institute of Normal Physiology; 3V. V. Zakusov Research Institute of Pharmacology, Moscow, Russia; 4School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK. Address for correspondence: [email protected]. T. V. Davydova 1
fect motor activity in the open-field test, which attested to their selective effect on memory formation [2]. Here we studied the effects of Abs-Glu on learning and spatial memory in the Morris water maze in relation to hippocampal and prefrontal cortical concentrations of biogenic amines, their metabolites, and amino acid neurotransmitters in aging C57BL/6 mice.
MATERIALS AND METHODS The study was performed on 12-month-old male C57BL/6 mice (n=24) weighing 32.2±1.8 g (supplied by the Research Institute of General Pathology and Pathophysiology). All animal experiments were carried out in co
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