Apolipoprotein E Gene Knock-out And High-fat Diet On IP3, IP3R-1 ＆ Aβ Expression In Neurons Of Mice's Hippocampal CA₁ ＆ Ca₃

Objective To observe the change of the IP3(inositol 1,4,5-triphosphate,IP3),IP3R-1's(inositol 1,4,5-triphosphate receptor-1,IP3R-1) & Aβ(amyloid proteinβ,Aβ)expression in neurons of the mice's hippocampal CA₁&CA₃, which had been treated by Apolipoprotein E gene knock-out(ApoE KO) and high-fat diet, and further explore the relationship between the ApoE KO and high-fat diet and the pathogenesis of neurodegenerative diseases. Methods Divided 30 C57BL/6J mice into 3 groups: the control group (group C),ApoE KO group (group KO),ApoE KO high-fat diet group (group KO-HF). After the established of mice model, weight and Plasma lipid of these mice were measured. The brain tissues of the mice were observed by using H-E staining, then immunohistochemistry staining, and computer image analysis. Resultsâ‘ The weight of C group (4.816±1.370),KO group (0.066±1.821),KO-HF group (23.631±5.215) is different (F=18.210,P<0.05).â‘¡The total cholesterol of C group (2.062±0.303),KO group (13.680±3.719),KO-HF group (31.821±2.933) is different (F=279.439,P<0.05).The triglyceride of C group (1.778±0.397),KO group (2.624±0.654),KO-HF group (3.006±0.238) is different (F=18.422,P<0.05).The low-density lipoprotein cholesterol of C group (0.697±0.550), KO group (2.367±0.571) , KO-HF group (5.165±1.071) is different (F=73.820, P<0.05) .â‘¢HE staining shows the hippocampal CA₁ &CA₃ pyramidal cells of the mice of the control group closely aligned, showing the cone-shaped, spherical. The KO group arranged irregularly, are slightly smaller cell body, the KO-HF group are somewhat sparse arrangement and smaller cell body.â‘£Immunohistochemistry staining shows IP3 and IP3R-1 of immunopositive material distributed in the cytoplasm of hippocampal neurons, the nucleus was negative. IP3 and IP3R-1 immunopositive material of the hippocampal CA₁ &CA₃ pyramidal cells of the mice of the control group are brownish yellow to brown color, the KO group are pale yellow to brown, the KO-HF group are pale yellow. Aβof the hippocampal CA₁ &CA₃ of the mice of the control group expressed in the cytoplasm of neurons, with light yellow granular, the KO group are dark yellow, the KO-HF group are dark brown yellow.⑤Image analysis shows the average optical density of IP3 in neurons of hippocampal CA₁&CA₃ in the C group (0.394±0.025) and (0.393±0.031),KO group (0.375±0.045)and (0.375±0.045),KO-HF group (0.341±0.033) and(0.343±0.032)is different (P﹤0.05);the average optical density of IP3R-1 in neurons of hippocampal CA₁&CA₃ in the C group(0.383±0.044)and (0.381±0.050),KO group (0.364±0.044) and (0.370±0.042),KO-HF group (0.338±0.013) and(0.338±0.012) is different(P﹤0.05);the average optical density of Aβin neurons of hippocampal CA₁&CA₃ in the C group(0.2865±0.011) and (0.2679±0.009),KO group (0.3354±0.032)and (0.3162±0.033),KO-HF group (0.3479±0.052)and(0.3299±0.035)is different (P﹤0.05). Conclusions ApoE KO and high-fat diet can decrease the expression level of IP3&IP3R-1 in neurons of hippocampal CA₁&CA₃ and increase the expression level of Aβ. These three proteins (IP3,IP3R-1&Aβ) may participate in the pathologic process in Neurodegenerative disease caused by the mice of ApoE KO and high-fat diet.