ABSTRACT
Objective:To compare the expression of myeloid cell trigger receptor expressed on myoid cell 2 (TREM2) in different brain regions of tyrosine kinase binding protein(TYROBP) knockout mice and wild-type mice at different months of age, and to explore the relationship between TREM2, TYROBP and early onset Alzheimer's disease(EOAD).Methods:Healthy TYROBP gene knockout mice were divided into three groups according to the results of gene sequencing: the homozygous (TYROBP -/-) group, the heterozygous (TYROBP -/+ ) group, and the wild type (WT) group.Western blot and RT-qPCR were used to detect the expression of TREM2 in prefrontal cortex and hippocampus of 2, 4 and 6 month old mice in the three groups and with 10 in each group at each time point. Results:(1) In the prefrontal cortex: Western blot and RT-qPCR results showed that compared with WT mice (2-month-old: (0.993±0.048), (1.654±0.033); 4-month-old: (0.503±0.019), (2.169±0.023); 6-month-old: (0.600±0.036), (1.468±0.057)), the levels of TREM2 protein and mRNA in 2-month-old TYROBP -/+ group ((0.746±0.062), (1.137±0.067)) and TYROBP -/- group ((0.661±0.028), (0.644±0.012)) were decreased.While in 4-month-old and 6-month-old TYROBP -/+ group (4-month-old: (1.140±0.006), (5.483±0.088); 6-month-old: (0.827±0.043), (3.020±0.082)) and TYROBP -/- group (4-month-old: (1.071±0.010), (3.012±0.150); 6-month-old: (0.627±0.026), (1.633±0.027)) were increased, especially in 4-month-old mice and the differences were statistically significant ( F=12.946, 134.445; 725.318, 289.202; 12.172, 202.791; all P<0.05). (2) In the hippocampus: Western blot results showed that compared with WT mice (2-month-old: (1.268±0.036); 4-month-old: (0.813±0.010); 6-month-old: (0.312±0.021)), the level of TREM2 protein in 2-month-old TYROBP -/+ group ((0.804±0.034)) and TYROBP -/- group ((0.534±0.020)) were decreased.While in 4-month-old and 6-month-old TYROBP -/+ group ((0.932±0.011); (0.769±0.031)) and TYROBP -/- group ((0.910±0.014); (0.609±0.018)) were increased, especially in 4-month-old mice and the differences were statistically significant ( F=142.807; 27.884; 94.067; all P<0.05). Conclusion:The expression level of TREM2 decreases in 2-month-old TYROBP gene knockout mice while increases in 4-month-old and 6-month-old TYROBP gene knockout mice.It is presumed that TREM2/TYROBP signal pathway participates in the pathological process of EOAD and plays different roles in different pathological stages of EOAD.