Effect of Anti-Glutamate Antibodies in Modeled Parkinsonian Syndrome
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Bulletin of Experimental Biology and Medicine, Vol. 169, No. 4, August, 2020 GENERAL PATHOLOGY AND PATHOPHYSIOLOGY
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Effect of Anti-Glutamate Antibodies in Modeled Parkinsonian Syndrome V. G. Kucheryanu, L. A. Vetrile, I. A. Zakharova, and N. A. Voronina
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 169, No. 4, pp. 411-415, April, 2020 Original article submitted June 27, 2019 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-phenyl1,2,3,6-tetrahydropyridine (MPTP) to C57BL/6J mice. Intranasal administration of antiglutamate 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. Key Words: Parkinson’s disease; parkinsonian syndrome; antibodies to glutamate; autoantibodies to glutamate; MPTP Parkinson’s disease is one of the most severe neurodegenerative diseases. The damage and death of dopaminergic neurons in the nigrostriatal system is considered as the main event in its pathogenesis [7]. One of the mechanisms of neuronal death in Parkinson’s disease is excitotoxicity caused by excess of extracellular glutamate and hyperactivation of glutamatergic receptors in the basal ganglia. Glutamate is the most abundant excitatory neurotransmitter in the brain. In excitatory synapses, glutamate is stored in vesicles and can be detected in both pre- and postsynaptic neurons and in glial cells, in particular, in astrocytes. Intracellular glutamate is relatively inactive; glutamate concentration in cells is 10,000fold higher than its extracellular concentration that is strictly regulated and maintained within a permissible range. Glutamate is not toxic, but under pathological conditions, e.g. in Parkinson’s disease at concentrations >1 mmol it produces a toxic effect by inducing excessive stimulation of glutamatergic receptors. Hyperactivation of ionotropic glutamate Research Institute of General Pathology and Pathophysiology, Moscow, Russia. Address for correspondence: [email protected]. V. G. Kucheryanu
receptors increases the membrane conductance for calcium ions. High intracellular level of Ca 2+ ions triggers a number of mechanisms including activation of enzymes (phospholipases, endonucleases, and proteases), induction of free radicals and oxidative stress, uncoupling of oxidative phosphorylation in mitochondria, and triggering of apoptosis, which ultimately lead to neuronal death [7,11]. Functional interaction of the dopaminergic and glutamatergic systems in the nigrostriatum plays an important role in the regulation of motor behavior. Our previous exper
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