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      Evaluation of the Effect of Hypericum triquetrifolium Turra on Memory Impairment Induced by Chronic Psychosocial Stress in Rats: Role of BDNF

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          Abstract

          Background

          Chronic psychosocial stress impairs memory function and leads to a depression-like phenotype induced by a persistent status of oxidative stress. Hypericum perforatum L. (St. John’s wort) is widely used to relieve symptoms of anxiety and depression; however, its long-term use is associated with adverse effects. Hypericum triquetrifolium Turra is closely related to H. perforatum. Both plants belong to Hypericaceae family and share many biologically active compounds. Previous work by our group showed that methanolic extracts of H. triquetrifolium have potent antioxidant activity as well as high hypericin content, a component that proved to have stress-relieving and antidepressant effects by other studies. Therefore, we hypothesized that H. triquetrifolium would reduce stress-induced cognitive impairment in a rat model of chronic stress.

          Objective

          To determine whether chronic treatment with H. triquetrifolium protects against stress-associated memory deficits and to investigate a possible mechanism.

          Methods

          The radial arm water maze (RAWM) was used to test learning and memory in rats exposed to daily stress using the resident–intruder paradigm. Stressed and unstressed rats received chronic H. triquetrifolium or vehicle. We also measured levels of brain-derived neurotrophic factor (BDNF) in the hippocampus, cortex and cerebellum.

          Results

          Neither chronic stress nor chronic H. triquetrifolium administration affected performance during acquisition. However, memory tests in the RAWM showed that chronic stress impaired different post-encoding memory stages. H. triquetrifolium prevented this impairment. Furthermore, hippocampal BDNF levels were markedly lower in stressed animals than in unstressed animals, and chronic administration of H triquetrifolium chronic administration protected against this reduction. No significant difference was observed in the effects of chronic stress and/or H. triquetrifolium treatment on BDNF levels in the cerebellum and cortex.

          Conclusion

          H. triquetrifolium extract can oppose stress-associated hippocampus-dependent memory deficits in a mechanism that may involve BDNF in the hippocampus.

          Most cited references120

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          A neurotrophic model for stress-related mood disorders.

          There is a growing body of evidence demonstrating that stress decreases the expression of brain-derived neurotrophic factor (BDNF) in limbic structures that control mood and that antidepressant treatment reverses or blocks the effects of stress. Decreased levels of BDNF, as well as other neurotrophic factors, could contribute to the atrophy of certain limbic structures, including the hippocampus and prefrontal cortex that has been observed in depressed subjects. Conversely, the neurotrophic actions of antidepressants could reverse neuronal atrophy and cell loss and thereby contribute to the therapeutic actions of these treatments. This review provides a critical examination of the neurotrophic hypothesis of depression that has evolved from this work, including analysis of preclinical cellular (adult neurogenesis) and behavioral models of depression and antidepressant actions, as well as clinical neuroimaging and postmortem studies. Although there are some limitations, the results of these studies are consistent with the hypothesis that decreased expression of BDNF and possibly other growth factors contributes to depression and that upregulation of BDNF plays a role in the actions of antidepressant treatment.
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            Place navigation impaired in rats with hippocampal lesions

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              The memory function of sleep.

              Sleep has been identified as a state that optimizes the consolidation of newly acquired information in memory, depending on the specific conditions of learning and the timing of sleep. Consolidation during sleep promotes both quantitative and qualitative changes of memory representations. Through specific patterns of neuromodulatory activity and electric field potential oscillations, slow-wave sleep (SWS) and rapid eye movement (REM) sleep support system consolidation and synaptic consolidation, respectively. During SWS, slow oscillations, spindles and ripples - at minimum cholinergic activity - coordinate the re-activation and redistribution of hippocampus-dependent memories to neocortical sites, whereas during REM sleep, local increases in plasticity-related immediate-early gene activity - at high cholinergic and theta activity - might favour the subsequent synaptic consolidation of memories in the cortex.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                dddt
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                01 December 2020
                2020
                : 14
                : 5299-5314
                Affiliations
                [1 ]Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology , Irbid 22110, Jordan
                [2 ]Institute of Anatomy II, Medical Faculty, Heinrich Heine Universität , Düsseldorf, Germany
                [3 ]Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology , Irbid 22110, Jordan
                [4 ]Department of Medical Laboratory Sciences, Jordan University of Science and Technology , Irbid 22110, Jordan
                [5 ]Integrative Life Sciences Doctoral Program, Department of Pathology, Virginia Commonwealth University , Richmond, VA, USA
                [6 ]College of Pharmacy, QU Health, Qatar University , Doha Qatar
                [7 ]Biomedical and Pharmaceutical Research Unit, QU Health, Qatar University , Doha, Qatar
                Author notes
                Correspondence: Feras Q Alali College of Pharmacy, Qatar University , Doha2713, Qatar Email Feras.alali@qu.edu.qa
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0002-2808-5099
                http://orcid.org/0000-0002-3006-3104
                http://orcid.org/0000-0002-9246-4974
                Article
                278153
                10.2147/DDDT.S278153
                7720289
                a276a22c-22ee-4eb4-87eb-ab0e178389d5
                © 2020 Alzoubi et al.

                This work is published by Dove Medical Press Limited, and licensed under a Creative Commons Attribution License. The full terms of the License are available at http://creativecommons.org/licenses/by/4.0/. The license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 21 August 2020
                : 14 November 2020
                Page count
                Figures: 5, References: 120, Pages: 16
                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine
                hypericum triquetrifolium,methanolic extract,stress,learning,memory,hippocampus,bdnf

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