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

Gruden, M. A.; Соловьева, Ольга Александровна; Кудрин, В. С.; Narkevich, V. B.; Шерстнев, В. В.

doi:10.1134/s1819712420010092

Cited by 2 publications

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“…The animals showed an increase in anxiety without signs of impaired motor activity, learning, and memory. At the same time, a significant decrease in the content of DA and an increase in the level of its metabolites were recorded in the frontal cortex, as well as a decrease in the concentration of DA and its metabolites in the hippocampus [11].…”

Section: Discussionmentioning

confidence: 76%

“…Six-month-old mice treated with α-syn oligomers reproduced individual preclinical manifestations of PD: increased anxiety, decreased dopamine content, and oppositely directed changes in the level of its metabolites in the hippocampus and frontal cortex. At the same time, the animals had no disturbances in motor activity, learning, and memory [10,11].…”

Section: Introductionmentioning

confidence: 86%

“…We used a battery of behavioral tests that we previously described [10,11]. On the 15th day from the beginning of the administration of the solutions, the animals from the experimental and control groups were placed in the "Open Field" (OF) apparatus (Columbus Instruments, Ohio, United States) once for 11 minutes (adaptation for 5 minutes; testing for the last 6 minutes).…”

Section: Methodsmentioning

confidence: 99%

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Neurochemical and Behavioral Effects of Alpha-Synuclein Oligomers in Three-Month-Old Mice

et al. 2021

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Parkinson's disease is a widespread, progressive, age-related neurodegenerative disease. The neurochemical basis of motor and non-motor disorder in Parkinson's disease is the dysfunction of many neurotransmitter systems of the brain and, first of all, the functional deficit and imbalance of monoaminergic systems, which result from the degradation and death of certain populations of nerve cells caused by misfolding of the α-synuclein protein and the action of its amyloidogenic neurotoxic conformations. Analysis of agerelated changes in monoaminergic systems and the development of motor and non-motor disorders at the preclinical and clinical stages of the disease are of particular interest. We studied the effect of α-synuclein oligomers administered intranasally for 14 days on locomotor activity, emotional state, short-and long-term memory, and the content and metabolism of dopamine, serotonin, and norepinephrine in the hippocampus, frontal cortex, and cerebellum of male C57Bl/6 mice at the age of 3 months. In behavioral experiments, the following tests were used: "open field," "novel object recognition," "passive avoidance," and "elevated plus maze." The content of monoamines and their metabolites in the brain tissue of animals was determined by high performance liquid chromatography with electromagnetic detection. It was found that mice treated with α-synuclein oligomers showed manifestations of affective-like behavior with signs of apathy. The animals showed no disorders in motor activity, short-term and long-term memory, and no changes in anxiety level. Oligomers of α-synuclein caused a significant decrease in the content of dopamine and its metabolites DOPAC and HVA in the frontal cortex, as well as a decrease in the concentration of the dopamine metabolite, 3-MT, and opposite directed changes in serotonin and dopamine metabolism in the hippocampus. However, a significant increase in the content of 3-MT in the cerebellum was recorded. We performed comparative analysis of the data obtained in this work and the results of our previous study of the neurochemical and behavioral effects of α-synuclein oligomers in 6-month-old mice. The results indicate that oligomers of α-synuclein, when administered chronically intranasally, induce non-motor disorders and neurochemical changes in mice of 3 months of age, which are also observed at the preclinical stage of PD.