Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy.
URT "Genomic of Diabetes", Institute of Experimental Endocrinology and Oncology, National Research Council, 80131 Naples, Italy.
Int J Mol Sci. 2021 Nov 16;22(22):12366. doi: 10.3390/ijms222212366.
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia, responsible for the onset of several long-term complications. Recent evidence suggests that cognitive dysfunction represents an emerging complication of DM, but the underlying molecular mechanisms are still obscure. Dopamine (DA), a neurotransmitter essentially known for its relevance in the regulation of behavior and movement, modulates cognitive function, too. Interestingly, alterations of the dopaminergic system have been observed in DM. This review aims to offer a comprehensive overview of the most relevant experimental results assessing DA's role in cognitive function, highlighting the presence of dopaminergic dysfunction in DM and supporting a role for glucotoxicity in DM-associated dopaminergic dysfunction and cognitive impairment. Several studies confirm a role for DA in cognition both in animal models and in humans. Similarly, significant alterations of the dopaminergic system have been observed in animal models of experimental diabetes and in diabetic patients, too. Evidence is accumulating that advanced glycation end products (AGEs) and their precursor methylglyoxal (MGO) are associated with cognitive impairment and alterations of the dopaminergic system. Further research is needed to clarify the molecular mechanisms linking DM-associated dopaminergic dysfunction and cognitive impairment and to assess the deleterious impact of glucotoxicity.
糖尿病（DM）是一种以高血糖为特征的慢性代谢性疾病，导致多种长期并发症的发生。最近的证据表明，认知功能障碍是 DM 的一种新出现的并发症，但潜在的分子机制仍不清楚。多巴胺（DA）作为一种主要参与行为和运动调节的神经递质，也调节认知功能。有趣的是，在 DM 中观察到了多巴胺能系统的改变。这篇综述旨在全面概述评估 DA 在认知功能中的作用的最相关实验结果，强调 DM 中存在多巴胺能功能障碍，并支持糖毒性在 DM 相关的多巴胺能功能障碍和认知障碍中的作用。几项研究证实了 DA 在动物模型和人类中的认知功能中的作用。同样，在实验性糖尿病的动物模型和糖尿病患者中也观察到了多巴胺能系统的显著改变。越来越多的证据表明，晚期糖基化终产物（AGEs）及其前体甲基乙二醛（MGO）与认知障碍和多巴胺能系统的改变有关。需要进一步的研究来阐明与 DM 相关的多巴胺能功能障碍和认知障碍相关的分子机制，并评估糖毒性的有害影响。
