Abstract
BackgroundChronic 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.ObjectiveTo determine whether chronic treatment with H. triquetrifolium protects against stress-associated memory deficits and to investigate a possible mechanism.MethodsThe 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.ResultsNeither 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.ConclusionH. triquetrifolium extract can oppose stress-associated hippocampus-dependent memory deficits in a mechanism that may involve BDNF in the hippocampus.
Highlights
In biological terms, stress can be defined as any condition that interrupts the equilibrium between an organism and its living environment and causes the release of stress mediators, including glucocorticoid hormones.[1,2] Stress triggers a sequence of events in the brain and peripheral nervous system to help the organism cope with and adapt to challenging situations.[3]
When the Hypericum and sts/Hypericum groups were each compared to the control group, there was a significant main effect of day (F4161 = 29.05, p < 0.001) but not group (F1161 = 3.197; p =0.076), with no group × day interaction (F4161 = 0.730; p > 0.05). These results indicate that chronic stress may have impaired learning process, and that this effect was prevented by chronic H. triquetrifolium administration
We examined the influence of chronic stress on hippocampus-dependent spatial learning and memory, and investigated whether the effects could be prevented by chronic administration of a methanolic extract of H. triquetrifolium Turra
Summary
Stress can be defined as any condition that interrupts the equilibrium between an organism and its living environment and causes the release of stress mediators, including glucocorticoid hormones.[1,2] Stress triggers a sequence of events in the brain and peripheral nervous system to help the organism cope with and adapt to challenging situations.[3]. Most studies agreed that prolonged stress negatively affects brain functions and impacts nearly every brain region.[9] Chronic stress impairs cognition in several aspects such as memory acquisition, consolidation and recall.[10] Most studies have focused on the relationship between prolonged stress and spatial ability. Decades of research have identified the hippocampus as an essential part for spatial ability, and showed that chronic stress influences hippocampal function, affecting spatial learning and memory.[11] The structure of the hippocampus was found to be sensitive to stress because of its high density of glucocorticoid receptors.[1] Under situa tions of prolonged stress, the hippocampus undergoes dis turbances in neurogenesis,[12] as well as neuronal atrophy,[13,14] leading to a corresponding reduction in the total number of neurons and their ramifications.[15,16].
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