Lactate supplementation after hypoglycemia alleviates cognitive dysfunction induced by recurrent non-severe hypoglycemia in diabetic mice

IF 4.6 2区医学 Q1 NEUROSCIENCES

Experimental Neurology Pub Date : 2024-10-29 DOI:10.1016/j.expneurol.2024.115037

Yubin Wu , Ruonan Gao , Qintao Huang , Cuihua Huang , Lijing Wang , Lu Lin , Guanlian He , Kejun Wu , Xiaoying Liu , Xiaohong Liu , Libin Liu

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引用次数: 0

Abstract

Recurrent non-severe hypoglycemia (RH) in diabetes is an independent risk factor for cognitive dysfunction. However, the mechanisms and potential therapeutic strategies remain poorly understood. In this study, we aimed to elucidate the mechanisms underlying RH-induced diabetic cognitive impairment. We investigated the effects of RH on lactate metabolism and cognitive function in male C57BL/6 J diabetic mice. After RH, diabetic mice showed decreased brain lactate and adenosine triphosphate levels, decreased expression of lactate transporter proteins MCT1 and MCT4, increased neuroapoptosis, and decreased astrocyte glycolysis in vitro. This was accompanied by increased neuronal mitochondrial reactive oxygen species levels, decreased mitochondrial COX IV activity, impaired mitochondrial morphology and function, impaired synaptic morphology, and decreased expression of synaptic plasticity proteins. Intraperitoneal lactic acid injection improved lactate transport restored neuronal mitochondrial morphology and function, upregulated synaptic plasticity proteins brain-derived neurotrophic factor and early growth response 1, enhanced synaptic ultrastructure, and ultimately improved cognitive dysfunction following RH in diabetic mice. These findings provide insights into the prevention and treatment of cognitive dysfunction in patients with diabetes mellitus caused by RH.

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低血糖后补充乳酸可减轻糖尿病小鼠因反复发生非严重低血糖而导致的认知功能障碍。

糖尿病患者反复出现的非严重低血糖（RH）是导致认知功能障碍的一个独立风险因素。然而，人们对其机制和潜在的治疗策略仍然知之甚少。本研究旨在阐明 RH 诱导糖尿病认知障碍的机制。我们研究了 RH 对雄性 C57BL/6 J 型糖尿病小鼠乳酸代谢和认知功能的影响。RH后，糖尿病小鼠的脑乳酸和三磷酸腺苷水平下降，乳酸转运蛋白MCT1和MCT4表达减少，神经凋亡增加，体外星形胶质细胞糖酵解减少。与此同时，神经元线粒体活性氧水平升高，线粒体 COX IV 活性降低，线粒体形态和功能受损，突触形态受损，突触可塑性蛋白表达减少。腹腔注射乳酸改善了乳酸转运，恢复了神经元线粒体的形态和功能，上调了突触可塑性蛋白脑源性神经营养因子和早期生长反应 1，增强了突触超微结构，最终改善了糖尿病小鼠 RH 后的认知功能障碍。这些发现为预防和治疗 RH 引起的糖尿病患者认知功能障碍提供了启示。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental Neurology 医学-神经科学

CiteScore

10.10

自引率

3.80%

发文量

258

审稿时长

42 days

期刊介绍： Experimental Neurology, a Journal of Neuroscience Research, publishes original research in neuroscience with a particular emphasis on novel findings in neural development, regeneration, plasticity and transplantation. The journal has focused on research concerning basic mechanisms underlying neurological disorders.