Abstract：
BACKGROUND: Changes in protein and lipid levels may occur in the Alzheimer\'s disease brain, and DHA can have beneficial effects on it. To investigate the impact of DHA dietary intervention on brain protein and lipid profile in ApoE-/- mice and C57 mice.
METHODS: Three-month-old ApoE-/- mice and C57 mice were randomly divided into two groups respectively, and fed with control diet and DHA-fortified diet for five months. Cortical TC, HDL-C and LDL-C levels and cholesterol metabolism-related protein expression were measured by ELISA or immunohistochemistry methods. Hippocampus were collected for proteomic and lipidomics analysis by LC-MS/MS and differential proteins and lipid metabolites were screened and further analyzed by GO functional annotation and KEGG pathway enrichment analysis.
RESULTS: DHA intervention decreased cortical TC level in both C57 and ApoE-/- mice (P < 0.05), but caused different change of cortical HDL-C, LDL-C level and LDL-C/HDL-C ratio in C57 and ApoE-/- mice (P < 0.05). Discrepant cortical and hippocampal LDLR, ABCG1, Lox1 and SORT1 protein expression was found between C57 and ApoE-/- mice (P < 0.05), and DHA treatment caused different changes of these proteins in C57 and ApoE-/- mice (P < 0.05). Differential hippocampal proteins and lipids profile were found in C57 and ApoE-/- mice before and after DHA treatment, which were mainly involved in vesicular transport and phospholipid metabolic pathways.
CONCLUSIONS: ApoE genetic defect caused abnormal cholesterol metabolism, and affected protein and lipid profile, as well as discrepant response of hippocampal protein and lipids profile in the brain of mice given DHA fortified diet intervention.
METHODS: Three-month-old ApoE-/- mice and C57 mice were randomly divided into two groups respectively, and fed with control diet and DHA-fortified diet for five months. Cortical TC, HDL-C and LDL-C levels and cholesterol metabolism-related protein expression were measured by ELISA or immunohistochemistry methods. Hippocampus were collected for proteomic and lipidomics analysis by LC-MS/MS and differential proteins and lipid metabolites were screened and further analyzed by GO functional annotation and KEGG pathway enrichment analysis.
RESULTS: DHA intervention decreased cortical TC level in both C57 and ApoE-/- mice (P < 0.05), but caused different change of cortical HDL-C, LDL-C level and LDL-C/HDL-C ratio in C57 and ApoE-/- mice (P < 0.05). Discrepant cortical and hippocampal LDLR, ABCG1, Lox1 and SORT1 protein expression was found between C57 and ApoE-/- mice (P < 0.05), and DHA treatment caused different changes of these proteins in C57 and ApoE-/- mice (P < 0.05). Differential hippocampal proteins and lipids profile were found in C57 and ApoE-/- mice before and after DHA treatment, which were mainly involved in vesicular transport and phospholipid metabolic pathways.
CONCLUSIONS: ApoE genetic defect caused abnormal cholesterol metabolism, and affected protein and lipid profile, as well as discrepant response of hippocampal protein and lipids profile in the brain of mice given DHA fortified diet intervention.
摘要：
背景：蛋白质和脂质水平的变化可能发生在阿尔茨海默病的大脑中，和DHA可以对它有有益的影响。探讨DHA饮食干预对ApoE-/-小鼠和C57小鼠脑蛋白和血脂谱的影响。
方法：将3月龄ApoE-/-小鼠和C57小鼠随机分为两组,并以控制饮食和DHA强化饮食喂养五个月。皮质TC,通过ELISA或免疫组织化学方法测量HDL-C和LDL-C水平以及胆固醇代谢相关蛋白的表达。通过LC-MS/MS收集海马进行蛋白质组学和脂质组学分析，筛选差异蛋白和脂质代谢产物，并通过GO功能注释和KEGG途径富集分析进行进一步分析。
结果：DHA干预降低了C57和ApoE-/-小鼠的皮质TC水平（P<0.05），但引起皮质HDL-C的不同变化，C57和ApoE-/-小鼠的LDL-C水平和LDL-C/HDL-C比值(P<0.05)。不同的皮质和海马LDLR，在C57和ApoE-/-小鼠之间发现ABCG1，Lox1和SORT1蛋白表达（P<0.05），和DHA处理在C57和ApoE-/-小鼠中引起这些蛋白的不同变化（P<0.05）。在DHA治疗前后，C57和ApoE-/-小鼠的海马蛋白和脂质分布差异。主要参与囊泡转运和磷脂代谢途径。
结论：ApoE基因缺陷导致胆固醇代谢异常，以及受影响的蛋白质和脂质分布，以及给予DHA强化饮食干预的小鼠大脑中海马蛋白和脂质谱的不同反应。
方法：将3月龄ApoE-/-小鼠和C57小鼠随机分为两组,并以控制饮食和DHA强化饮食喂养五个月。皮质TC,通过ELISA或免疫组织化学方法测量HDL-C和LDL-C水平以及胆固醇代谢相关蛋白的表达。通过LC-MS/MS收集海马进行蛋白质组学和脂质组学分析，筛选差异蛋白和脂质代谢产物，并通过GO功能注释和KEGG途径富集分析进行进一步分析。
结果：DHA干预降低了C57和ApoE-/-小鼠的皮质TC水平（P<0.05），但引起皮质HDL-C的不同变化，C57和ApoE-/-小鼠的LDL-C水平和LDL-C/HDL-C比值(P<0.05)。不同的皮质和海马LDLR，在C57和ApoE-/-小鼠之间发现ABCG1，Lox1和SORT1蛋白表达（P<0.05），和DHA处理在C57和ApoE-/-小鼠中引起这些蛋白的不同变化（P<0.05）。在DHA治疗前后，C57和ApoE-/-小鼠的海马蛋白和脂质分布差异。主要参与囊泡转运和磷脂代谢途径。
结论：ApoE基因缺陷导致胆固醇代谢异常，以及受影响的蛋白质和脂质分布，以及给予DHA强化饮食干预的小鼠大脑中海马蛋白和脂质谱的不同反应。
