Diabetic rats display cognition impairments accompanied by activation of NF-κB signalling and increased Aβ expression. Ghrelin has been suggested to improve cognition in diabetic rats. In this study, we investigated the role of ghrelin on cognition and NF-κB mediated Aβ production in diabetic rats. A diabetic rat model was established with streptozotocin (STZ) injection, and diabetic rats were intracerebroventricularly administered with ghrelin or (D-lys3)-GHRP-6 (DG). Our results showed that diabetic rats had cognition impairment in the Morris water maze test, accompanied by the higher expression of Aβ in the hippocampus. Western blot analysis showed that diabetic rats exhibited significantly decreased levels of GHSR-1a and protein phosphatase 1 (PP1) in the hippocampus and increased activation of the IKK/NF-κB/BACE1 pathway. Chronic ghrelin administration upregulated hippocampal PP1 expression, suppressed IKK/NF-κB/BACE1 mediated Aβ production, and improved cognition in STZ-induced diabetic rats. These effects were reversed by DG. Then, primary rat hippocampal neurons were isolated and treated with high glucose, followed by Ghrelin and DG, PP1 or IKK. Similar to the in vivo results, high glucose suppressed the expression levels of GHSR-1a and PP1, activated the IKK/NF-κB/BACE1 pathway, increased Aβ production. Ghrelin suppressed IKK/NF-κB/BACE1 induced Aβ production. This improvement was reversed by DG and a PP1 antagonist and was enhanced by the IKK antagonist. Our findings indicated that chronic ghrelin administration can suppress IKK/NF-κB/BACE1 mediated Aβ production in primary neurons with high glucose treatment and improve the cognition via PP1 upregulation in diabetic rats.

中文翻译：

---

慢性生长激素释放肽的给药可抑制STZ糖尿病大鼠中IKK /NF-κB/ BACE1介导的原代神经元Aβ产生，并通过上调PP1改善认知功能。

糖尿病大鼠显示出认知障碍，伴随着NF-κB信号的激活和Aβ表达的增加。Ghrelin已被建议改善糖尿病大鼠的认知。在这项研究中，我们调查了生长素释放肽对糖尿病大鼠认知和NF-κB介导的Aβ产生的作用。通过链脲佐菌素（STZ）注射建立糖尿病大鼠模型，并向脑室内施用生长激素释放肽或（D-lys3）-GHRP-6（DG）的糖尿病大鼠。我们的结果表明，糖尿病大鼠在莫里斯水迷宫测试中存在认知障碍，并伴有海马中Aβ的高表达。蛋白质印迹分析表明，糖尿病大鼠海马中GHSR-1a和蛋白磷酸酶1（PP1）的水平显着降低，并且IKK /NF-κB/ BACE1途径的激活增加。慢性生长激素释放肽给药可上调海马PP1的表达，抑制IKK /NF-κB/ BACE1介导的Aβ产生，并改善STZ诱导的糖尿病大鼠的认知。DG扭转了这些影响。然后，分离大鼠原代海马神经元并用高葡萄糖处理，然后用Ghrelin和DG，PP1或IKK处理。与体内结果相似，高葡萄糖抑制了GHSR-1a和PP1的表达水平，激活了IKK /NF-κB/ BACE1途径，增加了Aβ的产生。Ghrelin抑制了IKK /NF-κB/ BACE1诱导的Aβ产生。DG和PP1拮抗剂逆转了这种改善，而IKK拮抗剂则增强了这种改善。