State Key Laboratory of Medical Neurobiology & Institutes of Brain Science, Fudan University, Shanghai, China.
State Key Laboratory of Medical Neurobiology & Institutes of Brain Science, Fudan University, Shanghai, China.
Biochem Biophys Res Commun. 2020 Apr 9;524(3):525-532. doi: 10.1016/j.bbrc.2020.01.071. Epub 2020 Feb 1.
Diabetes mellitus (DM) is currently a major global health problem, which is associated with the development of cognitive dysfunction. However, although numerous clinical drugs for hyperglycemia have been used at present, safer and more effective therapeutic intervention strategies for diabetic cognitive impairments are still a huge challenge. Recently, several studies have indicated that a novel class of branched palmitic acid esters of hydroxyl stearic acids (PAHSAs) may have anti-diabetes and anti-inflammatory effects in insulin-resistant mice. Herein, whether the 9-PAHSA that one of the PAHSAs can attenuates DM-associated cognitive impairment in a mouse model of type 2 diabetes has been investigated. Our results showed that 9-PAHSA mildly prevented deficits of spatial working memory in Y-maze test while reversed the preference bias toward novel mice in Social choice test. Furthermore, the effect of REST on cognitive impairment of diabetes was explored for the first time. It was found that the expression of REST in diabetic mice increased, and the expression of target protein BDNF (Brain-derived neurotrophic factor) was decreased. After administration of 9-PAHSA, the situation was reversed. In summary, we conclude that exogenous supplement of 9-PAHSA can improve DM-related cognitive impairment to some extent, and the protective effect may be associated with decreased REST/NRSF (repressor element-1 silencing transcription factor/neuron-restrictive silence factor) and upregulated BDNF expression in frontal cortex.
糖尿病（DM）目前是一个主要的全球健康问题，与认知功能障碍的发展有关。然而，尽管目前已经有许多用于高血糖的临床药物，但对于糖尿病性认知障碍，更安全、更有效的治疗干预策略仍然是一个巨大的挑战。最近，有几项研究表明，一类新型的支链羟基硬脂酸棕榈酸酯（PAHSAs）可能对胰岛素抵抗的小鼠具有抗糖尿病和抗炎作用。在此，研究了其中一种 PAHSA-9-PAHSA 是否可以减轻 2 型糖尿病小鼠模型中与糖尿病相关的认知障碍。我们的结果表明，9-PAHSA 轻度预防了 Y 迷宫测试中空间工作记忆的缺陷，同时逆转了社交选择测试中对新老鼠的偏好偏向。此外，首次探索了 REST 对糖尿病认知障碍的影响。结果发现，糖尿病小鼠中 REST 的表达增加，而靶蛋白 BDNF（脑源性神经营养因子）的表达减少。给予 9-PAHSA 后，情况得到逆转。综上所述，我们得出结论，外源性补充 9-PAHSA 可以在一定程度上改善与糖尿病相关的认知障碍，其保护作用可能与额叶中 REST/NRSF（沉默转录因子/神经元限制沉默因子）减少和 BDNF 表达上调有关。
