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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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          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.


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


          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.


          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.


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

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          Most cited references 120

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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 human hippocampus and spatial and episodic memory.

              Finding one's way around an environment and remembering the events that occur within it are crucial cognitive abilities that have been linked to the hippocampus and medial temporal lobes. Our review of neuropsychological, behavioral, and neuroimaging studies of human hippocampal involvement in spatial memory concentrates on three important concepts in this field: spatial frameworks, dimensionality, and orientation and self-motion. We also compare variation in hippocampal structure and function across and within species. We discuss how its spatial role relates to its accepted role in episodic memory. Five related studies use virtual reality to examine these two types of memory in ecologically valid situations. While processing of spatial scenes involves the parahippocampus, the right hippocampus appears particularly involved in memory for locations within an environment, with the left hippocampus more involved in context-dependent episodic or autobiographical memory.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                01 December 2020
                : 14
                : 5299-5314
                [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

                © 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.

                Page count
                Figures: 5, References: 120, Pages: 16
                Original Research


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