Altered expression of glial markers, chemokines, and opioid receptors in the spinal cord of type 2 diabetic monkeys.
Altered expression of glial markers, chemokines, and opioid receptors in the spinal cord of type 2 diabetic monkeys.
复制标题
2型糖尿病猴的脊髓中神经胶质标记，趋化因子和阿片受体的表达改变。
DOI：
10.1016/j.bbadis.2016.10.007
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发表时间：
2017-01
影响因子：
6.2
通讯作者：
Ko, Mei-Chuan
中科院分区：
文献类型：
--
作者：
Kiguchi, Norikazu;Ding, Huiping;Peters, Christopher M.;Kock, Nancy D.;Kishioka, Shiroh;Cline, J. Mark;Wagner, Janice D.;Ko, Mei-Chuan
关键词：
神经炎症是糖尿病的病理基础，影响感觉处理。鉴于糖尿病患者疼痛的高患病率以及趋化因子和阿片类药物之间的串扰，了解糖尿病灵长类动物中枢神经系统中神经炎症相关介质是否失调是关键。因此，本研究的目的是研究与年龄匹配的非糖尿病猴（n=6）相比，自然发生的2型糖尿病猴（n=7）的脊髓和丘脑中胶质细胞标志物、趋化因子和阿片受体的mRNA表达水平是否发生改变。通过RT-qPCR方法，我们发现糖尿病猴脊髓背角（SDH）GFAP和IBA 1 mRNA表达水平较非糖尿病猴显著上调。在所有趋化因子中，三种趋化因子配体-受体系统，即，CCL 2-CCR 2、CCL 3-CCR 1/5和CCL 4-CCR 5在糖尿病猴的SDH中上调。此外，在SDH中，七种额外的趋化因子受体，即，CCR 4、CCR 6、CCR 8、CCR 10、CXCR 3、CXCR 5和CXCR 6也在糖尿病猴中上调。与此相反，MOP，KOP和DOP的表达水平，但不是NOP受体，在SDH的糖尿病猴下调，和丘脑的胶质细胞标记物，趋化因子和阿片类药物的变化较少。这些发现表明，神经炎症，表现为神经胶质细胞活化和同时上调多种趋化因子配体和受体，似乎是永久性的2型糖尿病猴。由于趋化因子和阿片类药物是重要的疼痛调节剂，这项首次在灵长类动物中进行的研究为确定靶向其信号级联的脊髓药物的功能功效提供了一个翻译桥梁。
Neuroinflammation is a pathological condition that underlies diabetes and affects sensory processing. Given the high prevalence of pain in diabetic patients and crosstalk between chemokines and opioids, it is pivotal to know whether neuroinflammation-associated mediators are dysregulated in the central nervous system of diabetic primates. Therefore, the aim of this study was to investigate whether mRNA expression levels of glial markers, chemokines, and opioid receptors are altered in the spinal cord and thalamus of naturally occurring type 2 diabetic monkeys (n=7) compared with age-matched non-diabetic monkeys (n=6). By using RT-qPCR, we found that mRNA expression levels of both GFAP and IBA1 were up-regulated in the spinal dorsal horn (SDH) of diabetic monkeys compared with non-diabetic monkeys. Among all chemokines, expression levels of three chemokine ligand-receptor systems, i.e., CCL2-CCR2, CCL3-CCR1/5, and CCL4-CCR5, were up-regulated in the SDH of diabetic monkeys. Moreover, in the SDH, seven additional chemokine receptors, i.e., CCR4, CCR6, CCR8, CCR10, CXCR3, CXCR5, and CXCR6, were also up-regulated in diabetic monkeys. In contrast, expression levels of MOP, KOP, and DOP, but not NOP receptors, were down-regulated in the SDH of diabetic monkeys, and the thalamus had fewer changes in the glial markers, chemokines and opioids. These findings indicate that neuroinflammation, manifested as glial activation and simultaneous up-regulation of multiple chemokine ligands and receptors, seems to be permanent in type 2 diabetic monkeys. As chemokines and opioids are important pain modulators, this first-in-primate study provides a translational bridge for determining the functional efficacy of spinal drugs targeting their signaling cascades.
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影响因子：
7.4
作者：
ARNER, S;MEYERSON, BA
通讯作者：
MEYERSON, BA
影响因子：
7.7
作者：
CORNBLATH, DR;HILLMAN, MA;HANSEN, BC
通讯作者：
HANSEN, BC
影响因子：
--
作者：
Kamenov, Zdravko Asenov;Parapunova, Rumyana Atanasova;Georgieva, Rumyana Taneva
通讯作者：
Georgieva, Rumyana Taneva
神经炎症驱动的慢性疼痛的新兴目标。
影响因子：
120.1
作者：
Ji, Ru-Rong;Xu, Zhen-Zhong;Gao, Yong-Jing
通讯作者：
Gao, Yong-Jing
影响因子：
10.9
作者：
Cai, Dongsheng
通讯作者：
Cai, Dongsheng