Abstract：
Diabetic cognitive impairment is a common complication in type 2 diabetes. Berberine (BBR) is an isoquinoline alkaloid that has been shown to have neuroprotective effects against diabetes. This study aimed to investigate the effect of BBR on the gray and white matter of the brain by using magnetic resonance imaging (MRI) and to explore the underlying mechanisms. The study used diabetic db/db mice and administered BBR (50 and 100 mg/kg) intragastrically for twelve weeks. Morris water maze was applied to examine cognitive function. T2-weighted imaging (T2WI) was performed to assess brain atrophy, and diffusion tensor imaging (DTI) combined with fiber tracking was conducted to monitor the structural integrity of the white matter, followed by histological immunostaining. Furthermore, the protein expressions of the phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (AKT)/ glycogen synthase kinase-3β (GSK-3β) were detected. The results revealed that BBR significantly improved the spatial learning and memory of the db/db mice. T2WI exhibited ameliorated brain atrophy in the BBR-treated db/db mice, as evidenced by reduced ventricular volume accompanied by increased hippocampal volumes. DTI combined with fiber tracking revealed that BBR increased FA, fiber density and length in the corpus callosum/external capsule of the db/db mice. These imaging findings were confirmed by histological immunostaining. Notably, BBR significantly enhanced the protein levels of phosphorylated AKT at Ser473 and GSK-3β at Ser9. Collectively, this study demonstrated that BBR significantly improved the cognitive function of the diabetic db/db mice through ameliorating brain atrophy and promoting white matter reorganization via AKT/GSK-3β pathway.
摘要：
糖尿病认知障碍是2型糖尿病的常见并发症。小檗碱（BBR）是一种异喹啉生物碱，已被证明对糖尿病具有神经保护作用。本研究通过磁共振成像(MRI)研究BBR对脑灰质和白质的影响,并探讨其作用机制。该研究使用糖尿病db/db小鼠并胃内施用BBR(50和100mg/kg)12周。应用Morris水迷宫检查认知功能。进行T2加权成像（T2WI）以评估脑萎缩，和扩散张量成像（DTI）结合纤维跟踪来监测白质的结构完整性，然后进行组织学免疫染色。此外，检测磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（AKT）/糖原合成酶激酶3β（GSK-3β）的蛋白表达。结果表明，BBR显着改善了db/db小鼠的空间学习和记忆能力。T2WI在BBR处理的db/db小鼠中表现出改善的脑萎缩，心室容量减少伴随海马容量增加证明了这一点。DTI结合纤维跟踪显示BBR增加了FA，db/db小鼠call体/外囊的纤维密度和长度。通过组织学免疫染色证实了这些影像学发现。值得注意的是,BBR显著增强Ser473处的磷酸化AKT和Ser9处的GSK-3β的蛋白质水平。总的来说，本研究表明，BBR通过AKT/GSK-3β通路改善脑萎缩和促进白质重组，显著改善糖尿病db/db小鼠的认知功能。
