Neurochemical and Behavioral Features of Action of Pre-Fibrillar Oligomeric Structures of α-Sinuclein in Adult Mice

Abstract

Abstract—The pre-fibrillar oligomeric structures of the α-synuclein protein formed during misfolding play an important role in the molecular pathogenesis of Parkinson’s disease and other age-dependent neurodegenerative diseases. We studied the effect of toxic α-synuclein oligomers administered intranasally for 14 days on the motor activity, learning, memory, and anxiety of adult (6-month-old) male C57Bl/6 mice, and on the levels and metabolism of monoamines and neurotransmitter amino acids in the hippocampus and the frontal cortex. We used the open field, passive avoidance, and elevated plus maze tests. The levels of monoamines and their metabolites, and neurotransmitter amino acids in the brain tissue of animals were determined by high performance liquid chromatography with electrochemical detection. It was found that oligomers of α‑synuclein cause an increase in anxiety in adult mice, a pronounced decrease in dopamine levels and oppositely directed changes in dopamine metabolite levels in the hippocampus and frontal cortex. No significant changes were found in learning indices and long-term memory, motor activity of animals, levels of noradrenaline, serotonin, or neurotransmitter amino acids in the studied brain structures after treatment with α-synuclein oligomers. We compared the experimental data and the results of our previous studies on the behavioral and neurochemical effects of oligomeric protein structures in aging 12-month-old mice. The possible mechanisms of the age-dependent effects of the α-synuclein oligomers are discussed.