Abstract:

Objective To examine the olfactory function of human α-synucleinA53T transgenic mice, and establish a model for olfactory dysfunction of early Parkinson´s disease. Methods Human α-synucleinA53T transgenic (TG) mice of different ages and their wildtype (WT) littermates were selected. Rotarod test was used to examine the voluntary motion of TG mice aged 10 months, and DAB method was employed to observe the dopaminergic neurons in substantia nigra in mice aged 10 months for identification of motor function. Odor discrimination and habituation tests were used to observe the short-term memory and habituation of familiar scents and identification of novel scents in mice. Long-term memory test with varied intervals was employed to examine the memory of exposed scents. Besides, buried pellet test was used to investigate the perception on scents of food, which reflected the odor threshold. Results Rotarod test and observation of dopaminergic neurons indicated that the voluntary motion in TG mice aged 10 months did not change. TG mice aged 6 months exhibited subtle deficit in odor discrimination, and there was no significant difference between the time of discrimination of novel scents and that of familiar scents (P=0.120). TG mice aged 10 months exhibited more significant deficit in discrimination of scents (P=0.295). The time for finding food in TG mice aged 6 months was longer than that in WT mice (P=0.015). The short memory and habituation of mice of different ages were normal, while TG mice aged 9 months exhibited decrease in long-term memory (60 min, 80 min and 100 min of test intervals). Conclusion Human α-synucleinA53T transgenic mice exhibit deficiency in olfaction before motion function alterations, including the aspects of discrimination, memory and perception of scents, which can well simulate the early olfactory disfunction in Parkinson´s disease.

Key words: Parkinson disease, olfactory dysfunction, animal model, α-synuclein