Environmental enrichment improves pain sensitivity, depression-like phenotype, and memory deficit in mice with neuropathic pain: role of NPAS4
Environmental enrichment improves pain sensitivity, depression-like phenotype, and memory deficit in mice with neuropathic pain: role of NPAS4
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环境丰富可改善神经性疼痛小鼠的疼痛敏感性、抑郁样表型和记忆缺陷：NPAS4 的作用
DOI：
10.1007/s00213-019-5187-6
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发表时间：
2019-02
影响因子：
3.4
通讯作者：
Zhi-qiang Zhou
中科院分区：
文献类型：
--
作者：
Xing-ming Wang;Zhi-qiang Zhou
患有神经性疼痛的患者具有更高的抑郁和认知能力下降的发生率。虽然环境丰富（EE）可能是有效的治疗神经性疼痛，其作用的确切机制仍然确定。该研究的目的是检查EE对神经性疼痛小鼠有益作用的分子机制。EE减弱了慢性压迫性损伤（CCI）后小鼠的痛阈降低、抑郁样表型和记忆缺陷。此外，EE减弱CCI后神经病理性疼痛小鼠海马神经发生减少和炎症增加。此外，替莫唑胺对成年海马神经发生的抑制拮抗了EE对神经病理性疼痛小鼠抑郁样表型和认知缺陷的有益作用。此外，脂多糖诱导的海马中肿瘤坏死因子-α（TNF-α）的增加拮抗EE对神经性疼痛小鼠这些行为异常的有益作用。通过靶向NPAS 4的慢病毒敲低海马中的NPAS 4（神经元PAS结构域蛋白4），阻断了EE在神经性疼痛小鼠中的这些有益作用。所有这些发现表明，海马NPAS 4在EE对神经病理性疼痛小鼠的疼痛敏感性、抑郁样表型和记忆缺陷的有益作用中起关键作用。因此，NPAS 4很可能成为慢性疼痛患者感知、情感和认知维度的新治疗靶点。
Patients suffering from neuropathic pain have a higher incidence of depression and cognitive decline. Although environment enrichment (EE) may be effective in the treatment of neuropathic pain, the precise mechanisms underlying its actions remain determined. The aim of the study was to examine the molecular mechanisms underlying the EE’s beneficial effects in mice with neuropathic pain. EE attenuated the pain threshold reduction, depression-like phenotype, and memory deficit in mice after chronic constriction injury (CCI). Furthermore, EE attenuated decreased neurogenesis and increased inflammation in the hippocampus of mice with neuropathic pain after CCI. Moreover, the suppression of adult hippocampal neurogenesis by temozolomide antagonized the beneficial effects of EE on depression-like phenotype and cognitive deficit in the mice with neuropathic pain. In addition, lipopolysaccharide-induced increase in tumor necrosis factor-α (TNF-α) in the hippocampus antagonized the beneficial effects of EE for these behavioral abnormalities in mice with neuropathic pain. Knock-down of NPAS4 (neuronal PAS domain protein 4) in the hippocampus by lentivirus targeting NPAS4 blocked these beneficial effects of EE in the mice with neuropathic pain. These all findings suggest that hippocampal NPAS4 plays a key role in the beneficial effects of EE on the pain sensitivity, depression-like phenotype, and memory deficit in mice with neuropathic pain. Therefore, it is likely that NPAS4 would be a new therapeutic target for perceptional, affective, and cognitive dimensions in patients with chronic pain.
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影响因子：
7.4
作者：
Bushnell MC;Case LK;Ceko M;Cotton VA;Gracely JL;Low LA;Pitcher MH;Villemure C
通讯作者：
Villemure C
DOI：
10.1523/jneurosci.5110-13.2014
发表时间：
2014-08
期刊：
The Journal of Neuroscience
影响因子：
--
作者：
Junfang Wu;Zaorui Zhao;B. Sabirzhanov;B. Stoica;Alok Kumar;Tao Luo;Jacob W. Skovira;A. Faden
通讯作者：
Junfang Wu;Zaorui Zhao;B. Sabirzhanov;B. Stoica;Alok Kumar;Tao Luo;Jacob W. Skovira;A. Faden
影响因子：
10.6
作者：
Alba-Delgado, Cristina;Llorca-Torralba, Meritxell;Berrocoso, Esther
通讯作者：
Berrocoso, Esther
影响因子：
6.1
作者：
R. Shepard;Kelsey A. Heslin;L. Coutellier
通讯作者：
R. Shepard;Kelsey A. Heslin;L. Coutellier
影响因子：
6.3
作者：
Choy, Fong Chan;Klaric, Thomas S.;Lewis, Martin D.
通讯作者：
Lewis, Martin D.