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Cited by 65Phytoestrogen effects and researchNeurogenesis and neuroplasticity mechanismsFlavonoids in Medical Research

Pharmacological administration of the isoflavone daidzein enhances cell proliferation and reduces high fat diet-induced apoptosis and gliosis in the rat hippocampus.

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Rivera, Patricia, Pérez-Martín, Margarita, Pavón, Francisco J., Serrano, Antonia, Crespillo, Ana, Cifuentes, Manuel, López-Ávalos, María-Dolores, Grondona, Jesús M. +4 more·2013·PLoS ONE
DOI 10.1371/journal.pone.0064750PMC PMC3669353
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Abstract

Soy extracts have been claimed to be neuroprotective against brain insults, an effect related to the estrogenic properties of isoflavones. However, the effects of individual isoflavones on obesity-induced disruption of adult neurogenesis have not yet been analyzed. In the present study we explore the effects of pharmacological administration of daidzein, a main soy isoflavone, in cell proliferation, cell apoptosis and gliosis in the adult hippocampus of animals exposed to a very high-fat diet. Rats made obese after 12-week exposure to a standard or high-fat (HFD, 60%) diets were treated with daidzein (50 mg kg(-1)) for 13 days. Then, plasma levels of metabolites and metabolic hormones, cell proliferation in the subgranular zone of the dentate gyrus (SGZ), and immunohistochemical markers of hippocampal cell apoptosis (caspase-3), gliosis (GFAP and Iba-1), food reward factor FosB and estrogen receptor alpha (ERα) were analyzed. Treatment with daidzein reduced food/caloric intake and body weight gain in obese rats. This was associated with glucose tolerance, low levels of HDL-cholesterol, insulin, adiponectin and testosterone, and high levels of leptin and 17β-estradiol. Daidzein increased the number of phospho-histone H3 and 5-bromo-2-deoxyuridine (BrdU)-ir cells detected in the SGZ of standard diet and HFD-fed rats. Daidzein reversed the HFD-associated enhanced immunohistochemical expression of caspase-3, FosB, GFAP, Iba-1 and ERα in the hippocampus, being more prominent in the dentate gyrus. These results suggest that pharmacological treatment with isoflavones regulates metabolic alterations associated with enhancement of cell proliferation and reduction of apoptosis and gliosis in response to high-fat diet.

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  • Previous HFD studies have been associated with increased microglial activity in wild-type mice.

    “Previous HFD studies have been associated with increased microglial activity in wild-type mice (Rivera et al., 2013; Wanrooy et al., 2018).”

    From Plcg2M28L Interacts With High Fat/High Sugar Diet to Accelerate Alzheimer’s Disease-Relevant Phenotypes in Mice (2022) · cites this paper as Rivera et al., 2013

    The Results (Figure 9; page unavailable) report significantly more Iba1-positive microglial cells in the hippocampi of HFD-fed rats, supporting the association with increased microglial activity. The cited study examined rats, not wild-type mice, so it does not support that population-specific part of the claim. (LLM, conf=0.88)

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Cited by

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Authors
Rivera, P., Pérez-Martín, M., Pavón, F. J., Serrano, A., Crespillo, A., Cifuentes, M., López-Ávalos, M.-D., Grondona, J. M., Vida, M., Fernández-Llebrez, P., de Fonseca, F. R., & Suárez, J.
Affiliations
  • Instituto de Salud Carlos III (ES)
  • Universidad de Málaga (ES)
Corresponding author
Suárez, Juan
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-05-31
Volume
8
Issue
5
Pages
e64750
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0064750
PMC
PMC3669353
OpenAlex
W2023889117
Cited by
65
References
4
Citations by year
2026: 2 · 2025: 3 · 2024: 7 · 2023: 3 · 2022: 3 · 2021: 7 · 2020: 7 · 2019: 6 · 2018: 5 · 2017: 6 · 2016: 7 · 2015: 5 · 2014: 3 · 2013: 1
FWCI
4.00
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • Repositorio Institucional de la Universidad de Málaga (University of Málaga) (submittedVersion, other-oa)
  • RISalud Institutional Health Repository of Andalucía (submittedVersion, other-oa)
Funders
  • European Commission (223713)
  • Directorate for Biological Sciences
  • Instituto de Salud Carlos III (CP12/03109)
  • European Regional Development Fund (CTS-433, RD06/0001/0000)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Phytoestrogen effects and research
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Health Sciences › Medicine › Pharmacology › Flavonoids in Medical Research
Keywords
daidzein, isoflavones, soy isoflavones, high-fat diet, obesity, hippocampus, adult neurogenesis, dentate gyrus subgranular zone, cell proliferation, apoptosis, caspase-3, gliosis, estrogen receptor alpha, FosB, food reward, leptin, estradiol, neuroprotection
MeSH terms
Animals, Calcium-Binding Proteins, Energy Intake, Glial Fibrillary Acidic Protein, Gliosis, Isoflavones, Male, Microfilament Proteins, Neuroglia, Neurons, Obesity, Plant Extracts, Glycine max, Gene Expression, Proto-Oncogene Proteins c-fos, Rats, Wistar, Apoptosis, Neuroprotective Agents, Dentate Gyrus, Estrogen Receptor alpha, Cell Proliferation, Rats, Caspase 3, Diet, High-Fat

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