Hyperexcitation of the glutamatergic neurons in lateral hypothalamus induced by chronic pain contributes to depression-like behavior and learning and memory impairment in male mice

IF 4.3 2区 医学 Q1 NEUROSCIENCES Neurobiology of Stress Pub Date : 2024-06-01 DOI:10.1016/j.ynstr.2024.100654
Lianghui Meng , Xuefeng Zheng , Keman Xie, Yifei Li, Danlei Liu, Yuanyuan Xu, Jifeng Zhang, Fengming Wu, Guoqing Guo
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Abstract

Chronic pain can induce mood disorders and cognitive dysfunctions, such as anxiety, depression, and learning and memory impairment in humans. However, the specific neural network involved in anxiety- and depression-like behaviors and learning and memory impairment caused by chronic pain remains poorly understood. In this study, behavioral test results showed that chronic pain induced anxiety- and depression-like behaviors, and learning and memory impairment in male mice. c-Fos immunofluorescence and fiber photometry recording showed that glutamatergic neurons in the LH of mice with chronic pain were selectively activated. Next, the glutamatergic neurons of LH in normal mice were activated using optogenetic and chemogenetic methods, which recapitulates some of the depressive-like behaviors, as well as memory impairment, but not anxiety-like behavior. Finally, inhibition of glutamatergic neurons in the LH of mice with chronic pain, effectively relieved anxiety- and depression-like behaviors and learning and memory impairment. Taken together, our findings suggest that hyperexcitation of glutamatergic neurons in the LH is involved in depression-like behavior and learning and memory impairment induced by chronic pain.

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慢性疼痛诱导的下丘脑外侧谷氨酸能神经元过度兴奋导致雄性小鼠出现抑郁样行为以及学习和记忆障碍
慢性疼痛可诱发人类情绪紊乱和认知功能障碍,如焦虑、抑郁以及学习和记忆障碍。然而,人们对慢性疼痛引起的焦虑和抑郁样行为以及学习和记忆障碍所涉及的特定神经网络仍然知之甚少。本研究的行为测试结果表明,慢性疼痛会诱发雄性小鼠的焦虑和抑郁样行为以及学习和记忆障碍。c-Fos免疫荧光和纤维光度记录显示,慢性疼痛小鼠LH中的谷氨酸能神经元被选择性激活。接着,使用光遗传学和化学遗传学方法激活了正常小鼠 LH 的谷氨酸能神经元,结果再现了一些类似抑郁的行为以及记忆损伤,但没有再现类似焦虑的行为。最后,抑制慢性疼痛小鼠 LH 中的谷氨酸能神经元可有效缓解焦虑和抑郁样行为以及学习和记忆障碍。综上所述,我们的研究结果表明,LH 中谷氨酸能神经元的过度兴奋参与了慢性疼痛诱发的抑郁样行为以及学习和记忆损伤。
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来源期刊
Neurobiology of Stress
Neurobiology of Stress Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
9.40
自引率
4.00%
发文量
74
审稿时长
48 days
期刊介绍: Neurobiology of Stress is a multidisciplinary journal for the publication of original research and review articles on basic, translational and clinical research into stress and related disorders. It will focus on the impact of stress on the brain from cellular to behavioral functions and stress-related neuropsychiatric disorders (such as depression, trauma and anxiety). The translation of basic research findings into real-world applications will be a key aim of the journal. Basic, translational and clinical research on the following topics as they relate to stress will be covered: Molecular substrates and cell signaling, Genetics and epigenetics, Stress circuitry, Structural and physiological plasticity, Developmental Aspects, Laboratory models of stress, Neuroinflammation and pathology, Memory and Cognition, Motivational Processes, Fear and Anxiety, Stress-related neuropsychiatric disorders (including depression, PTSD, substance abuse), Neuropsychopharmacology.
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