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慢性疼痛介导的认知障碍对青少年大鼠大脑葡萄糖代谢的影响。

Influence of Cerebral Glucose Metabolism by Chronic Pain-Mediated Cognitive Impairment in Adolescent Rats.

机构信息

Department of Anaesthesiology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, 430071, People's Republic of China.

Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences-Wuhan National Laboratory for Optoelectronics, Wuhan, Hubei, 430071, People's Republic of China.

出版信息

Mol Neurobiol. 2022 Jun;59(6):3635-3648. doi: 10.1007/s12035-022-02816-4. Epub 2022 Mar 31.

DOI:10.1007/s12035-022-02816-4
PMID:35355195
Abstract

Chronic pain during adolescence can lead to mental health disorders in adulthood, but the underlying mechanism is still unclear. Furthermore, the homeostasis of cerebral glucose metabolism and neurotransmitter metabolic kinetics are closely associated with cognitive development and pain progression. The present study investigated changes in cognitive function and glucose metabolism in adult rats, which had experienced chronic pain during their adolescence. Here, spared nerve injury (SNI) surgery was conducted in 4-week-old male rats. Mechanical nociceptive reflex thresholds were analyzed, and SNI chronic pain (SNI-CP) animals were screened. Based on animal behavioral tests (open field, three-chambered social, novel object recognition and the Y maze), the SNI-CP animals showed learning and memory impairment and anxiety-like behaviors, compared to SNI no chronic pain (SNI-NCP) animals. The cerebral glucose metabolism in the prefrontal cortex and hippocampus of adult SNI-CP animals was decreased with positron emission tomography/computed tomography. GABA and Glu levels in the metabolic kinetics study were significantly decreased in the hippocampus, frontal cortex, and temporal cortex, and the expression of GLUT3 and GLUT4 was also significantly downregulated in the prefrontal cortex and hippocampus of adult rats in the SNI-CP group. These findings suggest that the rats which suffered chronic pain during adolescence have lower cerebral glucose metabolism in the cortex and hippocampus, which could be related to cognitive function during the development of the central nervous system.

摘要

青少年时期的慢性疼痛会导致成年后患精神健康障碍,但潜在的机制仍不清楚。此外,大脑葡萄糖代谢和神经递质代谢动力学的内稳态与认知发展和疼痛进展密切相关。本研究探讨了经历青春期慢性疼痛的成年大鼠认知功能和葡萄糖代谢的变化。在这里,对 4 周龄雄性大鼠进行了 spared nerve injury(SNI)手术。分析机械性伤害感受反射阈值,并筛选出 SNI 慢性疼痛(SNI-CP)动物。基于动物行为测试(旷场、三箱社交、新物体识别和 Y 迷宫),与 SNI 无慢性疼痛(SNI-NCP)动物相比,SNI-CP 动物表现出学习和记忆障碍以及焦虑样行为。正电子发射断层扫描/计算机断层扫描显示,成年 SNI-CP 动物的前额叶皮质和海马体中的大脑葡萄糖代谢降低。代谢动力学研究中,海马体、额叶皮质和颞叶皮质中的 GABA 和 Glu 水平显著降低,成年大鼠 SNI-CP 组的前额叶皮质和海马体中 GLUT3 和 GLUT4 的表达也显著下调。这些发现表明,在青春期经历慢性疼痛的大鼠皮质和海马体的大脑葡萄糖代谢降低,这可能与中枢神经系统发育过程中的认知功能有关。

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