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      Dietary supplementation of soy germ phytoestrogens or estradiol improves spatial memory performance and increases gene expression of BDNF, TrkB receptor and synaptic factors in ovariectomized rats

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      1 , 3 , , 2 , 3 , 3 ,
      Nutrition & Metabolism
      BioMed Central

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          Abstract

          Background

          Estrogen or phytoestrogens treatment has been suggested to improve cognitive function of the brain in postmenopausal women. However, there is lack of information on the mechanism of such treatment on the central nervous system. The present study aimed to determine the effects of estradiol and soy germ phytoestrogens on spatial memory performance in ovariectomized rats and to explore the underlying mechanisms affecting the central nervous system.

          Methods

          Ovariectomized Sprague-Dawley rats were fed a basic diet supplemented with soy germ phytoestrogens (0.4 g/kg or 1.6 g/kg) or 17β-estradiol (0.15 g/kg) for 12 weeks. At the end of the experiment, animals were evaluated for their spatial learning and memory performance by the Morris Water Maze task. The expressions of brain-derived neurotrophic factor (BDNF) and synaptic formation proteins in the hippocampal tissue were estimated using RT-PCR and ELISA.

          Results

          It was found that rats supplemented with soy germ phytoestrogens or estradiol performed significantly better in spatial memory acquisition and retention when compared to the rats fed on the control diet. Estradiol or the high dose of phytoestrogens treatment significantly increased BDNF concentration and the mRNA levels for BDNF and its TrkB receptors as well as the synaptic formation proteins, synaptophysin, spinophilin, synapsin 1 and PSD-95, in the hippocampal tissue of the experimental animals. It was also found that phytoestrogens, in contrast to estradiol, did not show any significant effect on the vaginal and uteri.

          Conclusion

          Soy germ phytoestrogens, which may be a substitute of estradiol, improved spatial memory performance in ovariectomized rats without significant side-effects on the vaginal and uteri. The memory enhancement effect may relate to the increase in BDNF and the synaptic formation proteins expression in the hippocampus of the brain.

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          Most cited references28

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          Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus.

          Recent studies suggest that stress-induced atrophy and loss of hippocampal neurons may contribute to the pathophysiology of depression. The aim of this study was to investigate the effect of antidepressants on hippocampal neurogenesis in the adult rat, using the thymidine analog bromodeoxyuridine (BrdU) as a marker for dividing cells. Our studies demonstrate that chronic antidepressant treatment significantly increases the number of BrdU-labeled cells in the dentate gyrus and hilus of the hippocampus. Administration of several different classes of antidepressant, but not non-antidepressant, agents was found to increase BrdU-labeled cell number, indicating that this is a common and selective action of antidepressants. In addition, upregulation of the number of BrdU-labeled cells is observed after chronic, but not acute, treatment, consistent with the time course for the therapeutic action of antidepressants. Additional studies demonstrated that antidepressant treatment increases the proliferation of hippocampal cells and that these new cells mature and become neurons, as determined by triple labeling for BrdU and neuronal- or glial-specific markers. These findings raise the possibility that increased cell proliferation and increased neuronal number may be a mechanism by which antidepressant treatment overcomes the stress-induced atrophy and loss of hippocampal neurons and may contribute to the therapeutic actions of antidepressant treatment.
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            A molecular and cellular theory of depression.

            Recent studies have begun to characterize the actions of stress and antidepressant treatments beyond the neurotransmitter and receptor level. This work has demonstrated that long-term antidepressant treatments result in the sustained activation of the cyclic adenosine 3',5'-monophosphate system in specific brain regions, including the increased function and expression of the transcription factor cyclic adenosine monophosphate response element-binding protein. The activated cyclic adenosine 3',5'-monophosphate system leads to the regulation of specific target genes, including the increased expression of brain-derived neurotrophic factor in certain populations of neurons in the hippocampus and cerebral cortex. The importance of these changes is highlighted by the discovery that stress can decrease the expression of brain-derived neurotrophic factor and lead to atrophy of these same populations of stress-vulnerable hippocampal neurons. The possibility that the decreased size and impaired function of these neurons may be involved in depression is supported by recent clinical imaging studies, which demonstrate a decreased volume of certain brain structures. These findings constitute the framework for an updated molecular and cellular hypothesis of depression, which posits that stress-induced vulnerability and the therapeutic action of antidepressant treatments occur via intracellular mechanisms that decrease or increase, respectively, neurotrophic factors necessary for the survival and function of particular neurons. This hypothesis also explains how stress and other types of neuronal insult can lead to depression in vulnerable individuals and it outlines novel targets for the rational design of fundamentally new therapeutic agents.
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              Loss of the presynaptic vesicle protein synaptophysin in hippocampus correlates with cognitive decline in Alzheimer disease.

              We tested the hypothesis that synaptic defects in the hippocampus of individuals with Alzheimer disease (AD) correlate with the severity of cognitive impairment. Three postmortem groups were studied: controls with normal and stable cognition; cognitively intact subjects with senile plaque densities diagnostic for possible AD (p-AD) and neurofibrillary changes characteristic of early AD (Braak stage III); and individuals with definite AD and neurofibrillary changes typical of incipient to severe AD (Braak stage III, V, or VI). Synaptophysin (a presynaptic vesicle protein) levels were quantified by immunoblotting of synaptic membrane fractions isolated from hippocampus, entorhinal cortex, caudate nucleus, and occipital cortex. Average synaptophysin levels were reduced in hippocampus when comparing definite AD to controls (55%, p < 0.0001), p-AD to control (25%, p < 0.005), and definite AD to p-AD (30%, p < 0.05), but levels in entorhinal cortex, occipital cortex, and caudate nucleus were either unchanged or less significantly altered than in hippocampus. By univariate analysis, hippocampal synaptophysin levels correlated with neuropsychological measurements, including Mini-mental state examination scores (r = 0.83, p < 0.0001) and Blessed scores (r = 0.74, P < 0.001), and with senile plaque densities (r = 0.89, p < 0.0001). We conclude that synaptic abnormalities in the hippocampus correlate with the severity of neuropathology and memory deficit in individuals with AD, and that this defect may predate neuropsychological evidence for cognitive impairment early in AD.
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                Author and article information

                Journal
                Nutr Metab (Lond)
                Nutrition & Metabolism
                BioMed Central
                1743-7075
                2010
                15 September 2010
                : 7
                : 75
                Affiliations
                [1 ]Dept. of Nutrition, Guangdong Academy of Medical Sciences, Guangdong General Hospital, No.106, Zhongshan Er Road, Guangzhou 510080, China
                [2 ]Food Safety Section, Wuhan Centres for Disease Prevention and Control, No.24 JiangHan Bei Road, Wuhan 430022, China
                [3 ]School of Biological Sciences, The University of Hong Kong, Hong Kong SAR, China
                Article
                1743-7075-7-75
                10.1186/1743-7075-7-75
                2949863
                20843342
                dafe02a2-889d-4ddd-84a9-16b357e7d274
                Copyright ©2010 Pan et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 7 July 2010
                : 15 September 2010
                Categories
                Research

                Nutrition & Dietetics
                Nutrition & Dietetics

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