Dynamic changes of gait parameters in C57BL/6J mice after intranasal administration of oligomeric forms of alpha-synuclein protein
Abstract
Gait disorders are characteristic, common, and most disabling motor symptoms of Parkinson's disease (PD). PD is a widespread chronic, progressive neurodegenerative disease. Manifestations of gait disorders are used to predict the development and outcome of the disease and to evaluate the effect of treatment. Studies of long-term changes in gait disorders on experimental models of PD are scarce and limited to short periods that cannot be compared to chronic, long-term course of the disease.
The aim of this work was to study gait disorders and their changes during a nine-month period on a PD model produced by chronic intranasal administration of α-synuclein oligomers to mature mice.
Materials and methods. A solution of recombinant α-synuclein oligomers (or saline (S) in the control group) was administered intranasally for 14 days to male 3-month-old C57Bl/6 mice, followed by gait testing (modified "footprint test") at ages of 4, 9, and 12 months. The RecognitionOfSteps and EthoVision software was used for gait analysis.
Results. At age of 4 months, the mice treated with α-synuclein oligomers, compared with the animals treated with S, showed initial manifestations of gait disorders, a tendency to reducing the step length of the hindlimbs and the length of the first step of the right hindlimb; at age of 9 months, one of the main gait disorders was found, decreases in the step length of all limbs; at age of 12 months, signs of gait instability were observed, increased distance between the centers of the right paw prints, increased step width of the hindlimbs, and increased average relative meander of the path.
Conclusion. In experimental modeling of PD by chronic intranasal administration of α-synuclein oligomers, three-month-old male mice demonstrate progressive gait disorders and their specific features during the nine-month study period. These disorders are similar to clinical manifestations of progressive gait dysfunction observed in the early and advanced PD and age-dependent.
