Changes in motor symptoms and cognitive function in α-synuclein A53T transgenic mice at different months of age
Objective To investigate the changes in motor symptoms and cognitive levels in α-synuclein A53T transgenic mice at different months of age and possible mechanisms.Methods The α-synuclein A53T transgenic mice and wild C57/BL6J mice,aged 6 months,were selected.The open field test and the rotarod test were used to observe the motor function and emotional response of mice;fear conditioning and the novel object recognition test were used to observe the cognitive function of mice;Western blotting was used to measure the expression level of M1 cholinergic receptor in the hippocampus of the mice in the two groups,and the transcriptome method was used to observe the difference in gene ex-pression in the hippocampus between the two groups.Results Behavioral experiments showed that compared with the wild-type mice,the A53T transgenic mice showed cognitive dysfunction at 12 months of age[novel object recognition test:(36.74±13.33)vs(46.90±6.58),t=-2.368,P=0.027],and this phenomenon occurred before motor symptoms.West-ern blotting showed that there was no significant difference in the level of M1 cholinergic receptor in the hippocampus be-tween the A53T transgenic mice and the wild-type mice(P=0.537).The transcriptome analysis identified 290 differen-tially expressed genes between the two groups,among which there were 20 genes with significant difference,and the sig-nificantly downregulated gene sets in the hippocampus of A53T mice were mainly involved in anti-cellular inflammatory re-sponse and antioxidant level.Conclusion Cognitive dysfunction in A53T transgenic mice occurs earlier than motor symp-toms,with a relatively late time node.Transcriptome tests suggest that cellular inflammatory response and oxidative stress injury might be involved in the early pathological process of cognitive impairment in A53T mice.
国家科技期刊平台
NSTL
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