17
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Anxiolytic Effects of 8-O-Acetyl Shanzhiside Methylester on Acute and Chronic Anxiety via Inflammatory Response Inhibition and Excitatory/Inhibitory Transmission Imbalance

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Anxiety leads to a global decline in quality of life and increase in social burden. However, treatments are limited, because the molecular mechanisms underlying complex emotional disorders are poorly understood. We explored the anxiolytic effects of 8-O-acetyl shanzhiside methylester (8-OaS), an active component in Lamiophlomis rotata ( L. rotata; Benth.) or Kudo, a traditional herb that has been shown to be effective in the clinical treatment of chronic pain syndromes in China. Two mouse anxiety models were used: forced swimming stress (FSS)–induced anxiety and complete Freund’s adjuvant (CFA)–induced chronic inflammatory pain. All animal behaviors were analyzed on the elevated plus maze and in the open-field test. 8-OaS significantly ameliorated anxiety-like behaviors in both anxiety models and inhibited the translation enhancement of GluN2A, GluN2B, and PSD95. Moreover, a reduction in GABA receptors disrupted the excitatory/inhibitory (E/I) balance in the basolateral amygdala (BLA), indicated by increased excitatory and decreased inhibitory presynaptic release. 8-OaS also blocked microglia activation and reduced the phosphorylation of p38, c-Jun N-terminal kinase (JNK), NF-κB p65, and tumor necrosis factor alpha (TNF-α) in the BLA of anxiety mice. 8-OaS exhibits obvious anxiolytic effects by regulating the excitatory/inhibitory (E/I) synaptic transmission and attenuating inflammatory responses in the BLA.

          Related collections

          Most cited references46

          • Record: found
          • Abstract: found
          • Article: not found

          Stress and disorders of the stress system.

          All organisms must maintain a complex dynamic equilibrium, or homeostasis, which is constantly challenged by internal or external adverse forces termed stressors. Stress occurs when homeostasis is threatened or perceived to be so; homeostasis is re-established by various physiological and behavioral adaptive responses. Neuroendocrine hormones have major roles in the regulation of both basal homeostasis and responses to threats, and are involved in the pathogenesis of diseases characterized by dyshomeostasis or cacostasis. The stress response is mediated by the stress system, partly located in the central nervous system and partly in peripheral organs. The central, greatly interconnected effectors of this system include the hypothalamic hormones arginine vasopressin, corticotropin-releasing hormone and pro-opiomelanocortin-derived peptides, and the locus ceruleus and autonomic norepinephrine centers in the brainstem. Targets of these effectors include the executive and/or cognitive, reward and fear systems, the wake-sleep centers of the brain, the growth, reproductive and thyroid hormone axes, and the gastrointestinal, cardiorespiratory, metabolic, and immune systems. Optimal basal activity and responsiveness of the stress system is essential for a sense of well-being, successful performance of tasks, and appropriate social interactions. By contrast, excessive or inadequate basal activity and responsiveness of this system might impair development, growth and body composition, and lead to a host of behavioral and somatic pathological conditions.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Control of synaptic strength by glial TNFalpha.

            Activity-dependent modulation of synaptic efficacy in the brain contributes to neural circuit development and experience-dependent plasticity. Although glia are affected by activity and ensheathe synapses, their influence on synaptic strength has largely been ignored. Here, we show that a protein produced by glia, tumor necrosis factor alpha (TNFalpha), enhances synaptic efficacy by increasing surface expression of AMPA receptors. Preventing the actions of endogenous TNFalpha has the opposite effects. Thus, the continual presence of TNFalpha is required for preservation of synaptic strength at excitatory synapses. Through its effects on AMPA receptor trafficking, TNFalpha may play roles in synaptic plasticity and modulating responses to neural injury.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Differential regulation of AMPA receptor and GABA receptor trafficking by tumor necrosis factor-alpha.

              The proinflammatory cytokine tumor necrosis factor-alpha (TNFalpha) causes a rapid exocytosis of AMPA receptors in hippocampal pyramidal cells and is constitutively required for the maintenance of normal surface expression of AMPA receptors. Here we demonstrate that TNFalpha acts on neuronal TNFR1 receptors to preferentially exocytose glutamate receptor 2-lacking AMPA receptors through a phosphatidylinositol 3 kinase-dependent process. This increases excitatory synaptic strength while changing the molecular stoichiometry of synaptic AMPA receptors. Conversely, TNFalpha causes an endocytosis of GABA(A) receptors, resulting in fewer surface GABA(A) receptors and a decrease in inhibitory synaptic strength. These results suggest that TNFalpha can regulate neuronal circuit homeostasis in a manner that may exacerbate excitotoxic damage resulting from neuronal insults.
                Bookmark

                Author and article information

                Contributors
                minggao@fmmu.edu.cn
                yangqifmmu@126.com
                Journal
                Neurotox Res
                Neurotox Res
                Neurotoxicity Research
                Springer US (New York )
                1029-8428
                1476-3524
                4 May 2020
                4 May 2020
                2020
                : 38
                : 4
                : 979-991
                Affiliations
                [1 ]GRID grid.233520.5, ISNI 0000 0004 1761 4404, Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, , the Fourth Military Medical University, ; Xi’an, 710038 Shaanxi Province People’s Republic of China
                [2 ]GRID grid.233520.5, ISNI 0000 0004 1761 4404, Department of Chemistry, School of Pharmacy, , the Fourth Military Medical University, ; Xi’an, 710032 China
                [3 ]GRID grid.233520.5, ISNI 0000 0004 1761 4404, Student Brigade, , the Fourth Military Medical University, ; Xi’an, 710032 China
                [4 ]GRID grid.233520.5, ISNI 0000 0004 1761 4404, Department of Pharmacy, Xijing Hospital, , the Fourth Military Medical University, ; Xi’an, 710032 China
                Article
                203
                10.1007/s12640-020-00203-2
                7591445
                32367473
                f9d97a01-d00e-4973-ac41-b30e36432191
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 2 February 2020
                : 24 March 2020
                : 7 April 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81801079
                Award ID: 81870893
                Award Recipient :
                Funded by: National Postdoctoral Program for Innovative Talents
                Award ID: BX20160025
                Award Recipient :
                Categories
                Original Article
                Custom metadata
                © Springer Science+Business Media, LLC, part of Springer Nature 2020

                Neurosciences
                anxiety,8-o-acetyl shanzhiside methylester,excitatory/inhibitory balance,basolateral amygdala,inflammatory response

                Comments

                Comment on this article