Short reportEstradiol and soy extract increase the production of new cells in the dentate gyrus of old rats
Introduction
In agreement with animals studies, estrogen replacement therapy (ERT) has been shown to increase memory and cognitive function in healthy postmenopausal women (Wise, 2003). However, the Women's Health Initiative (WHI) randomized trial, suggests an increased risk of dementia as a result of long-lasting hormonal treatment with conjugated equine estrogen plus medroxyprogesterone acetate (Shumaker et al., 2003, Yaffe, 2003). The results of the WHI study emphasize the need for a better understanding on the effects of sex hormones in the aged brain and after a long period of gonadal hormonal deprivation. Furthermore, dietary phytoestrogens, compounds with weak estrogenic or antiestrogenic activity such as the isoflavones contained in soy extracts (Dixon, 2004), have been proposed as alternatives of HRT (Huntley and Ernst, 2004). Neuroprotective properties of soy extracts and phytoestrogens have been documented in animal and cellular models (Wang et al., 2001, Gelinas and Martinoli, 2002, Linford and Dorsa, 2002, Zhao et al., 2002, Zeng et al., 2004). However, it is unknown whether the aged brain is still responsive to the actions of these compounds. In this study, we have assessed cell proliferation in the dentate gyrus of the hippocampus of old rats after estradiol or soy extract treatments. This parameter was selected, since estradiol regulates cell proliferation in this brain area in young female rodents (Tanapat et al., 1999, Banasr et al., 2001, Ormerod and Galea, 2001). The dentate gyrus is one of the brain areas where neurogenesis is maintained through adult life in rodents. However, cell proliferation in the dentate gyrus dramatically decreases in old age (Kuhn et al., 1996) and it is unknown whether estrogens may affect this aging-associated process.
Section snippets
Material and methods
Wistar albino female rats from our in house colony (Complutense University) were raised and maintained on 12:12 h light:dark cycle. The animals were fed a normal rat chow (A.04; Panlab, Barcelona, Spain) and had free access to tap water. All procedures used in these experiments followed the European Union normative (86/609/EEC) and were approved by the Institutional Animal Care Committee of the Complutense University.
To reduce circulating sex steroid levels, animals were bilaterally
Results
Cells incorporating BrdU were found in the dentate gyrus of all studied animals (Fig. 1). BrdU-positive nuclei were found in the hilus, in the subgranular zone (SGZ) and in the inner part of the granule cell layer (GCL). BrdU cells in the SGZ/GCL were in most cases present in clusters and were always located at the border between the GCL and the hilus. BrdU-immunoreactive nuclei in this location were of bigger size than BrdU-immunoreactive nuclei in the hilus, which probably correspond to glial
Discussion
Our findings, showing a strong decrease in the number of BrdU-labeled cells in the GCL/SGZ of the dentate gyrus of Wistar rats between 18 and 22 months of age, are in agreement with previous studies reporting a decline with advancing age in hippocampal neurogenesis in rodents (Kuhn et al., 1996). Estrogen is known to promote hippocampal neurogenesis in young female rats (Tanapat et al., 1999, Banasr et al., 2001, Ormerod and Galea, 2001). Our present findings indicate that the hormone also
Acknowledgements
This study has been carried out with financial support from Comunidad de Madrid (CAM 08.5/0062/2001; 08.5/0002.2/2003), IMSERSO, MTAS 2002, Ministerio de Ciencia y Tecnología (SAF 2002-00652) and the Commission of the European Communities, specific RTD programme ‘Quality of Life and Management of Living Resources’ (QLK6-CT-2000-00179).
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