Expressions of triggering receptor expressed on myeloid cell 2 in different brain regions in tyrosine kinase binding protein gene knockout mice

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. Key words: Tyrosine kinase binding protein; Triggering receptor expressed on myeloid cell 2; Alzheimer's disease; Mice