Liu Zhuo, Zhao Hongqing, Liu Jian, Han Yuanshan, Wang Yuhong
Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha, Hunan, China.
Hunan University of Chinese Medicine, Science and Technology Innovation Center, Changsha, Hunan, China.
Evid Based Complement Alternat Med. 2022 Aug 29;2022:8980627. doi: 10.1155/2022/8980627. eCollection 2022.
To investigate the mechanism via which FKN/CX3CR1 signaling abnormalities mediate N-methyl-D-aspartic acid receptor (NMDA) overexcitation-induced hippocampal neuronal injury in diabetic rats complicated with depression (DD).
Sixty rats were randomly divided into 5 groups. The depression-like behaviors of the rats were evaluated by open field test and Morris water maze. The pathological changes of hippocampus in DD rats were observed by HE staining. The blood levels of inflammatory factors (IL-1, TNF-, and IL-6) and neurotransmitters (D-serine and glutamic acid) were determined by enzyme-linked immunosorbent assay (ELISA). The expressions of BDNF, A1 receptor (A1R), A2 receptor (A2R), A3 receptor (A3R), calmodulin dependent kinase II (CaMKII), CX3CR1, CX3CL1 (FKN), NR2A, and NR2B proteins were detected by immunohistochemistry and Western-blotting.
Compared with the normal control group, blood glucose level increased significantly and body weight decreased in T2DM group and T2DMC group. In addition, the number of spontaneous activities significantly decreased and the capability of learning and memory was attenuated in T2DMC group and Chronic Stress group. The blood levels of IL-1, TNF-, IL-6, glutamate (Glu), and D-serine significantly increased in each model group. After intervention with CX3CR1 antibody, the expressions of BDNF, CaMK II, A1R, and A3R increased and those of A2R, CX3CR1, FKN, NR2A, and NR2B decreased.
In the diabetic state, the binding of FKN to CX3CR1 increases, which regulates a variety of adenosine receptors. When it exerts its effect on neurons, the overactivation of NR results in neuronal injury and causes depression.
探讨FKN/CX3CR1信号异常介导N-甲基-D-天冬氨酸受体（NMDA）过度兴奋诱导糖尿病合并抑郁症（DD）大鼠海马神经元损伤的机制。
将60只大鼠随机分为5组。通过旷场试验和莫里斯水迷宫评估大鼠的抑郁样行为。采用HE染色观察DD大鼠海马的病理变化。用酶联免疫吸附测定法（ELISA）测定炎症因子（IL-1、TNF-α和IL-6）和神经递质（D-丝氨酸和谷氨酸）的血药浓度。通过免疫组织化学和蛋白质印迹法检测脑源性神经营养因子（BDNF）、A1受体（A1R）、A2受体（A2R）、A3受体（A3R）、钙调蛋白依赖性激酶II（CaMKII）、CX3CR1、CX3CL1（FKN）、NR2A和NR2B蛋白的表达。
与正常对照组相比，T2DM组和T2DMC组血糖水平显著升高，体重下降。此外，T2DMC组和慢性应激组的自发活动次数显著减少，学习记忆能力减弱。各模型组IL-1、TNF-α、IL-6、谷氨酸（Glu）和D-丝氨酸的血药浓度显著升高。用CX3CR1抗体干预后，BDNF、CaMK II、A1R和A3R的表达增加，A2R、CX3CR1、FKN、NR2A和NR2B的表达降低。
在糖尿病状态下，FKN与CX3CR1的结合增加，调节多种腺苷受体。当它作用于神经元时，NR的过度激活导致神经元损伤并引起抑郁。
