Estrogen and exercise interact to regulate brain‐derived neurotrophic factor mRNA and protein expression in the hippocampus
Abstract
We investigated the possibility that estrogen and exercise interact in the hippocampus and regulate brain‐derived neurotrophic factor (BDNF), a molecule increasingly recognized for its role in plasticity and neuron function. An important aspect of this study is to examine the effect of different time intervals between estrogen loss and estrogen replacement intervention. We demonstrate that in the intact female rat, physical activity increases hippocampal BDNF mRNA and protein levels. However, the exercise effect on BDNF up‐regulation is reduced in the absence of estrogen, in a time‐dependent manner. In addition, voluntary activity itself is stimulated by the presence of estrogen. In exercising animals, estrogen deprivation reduced voluntary activity levels, while estrogen replacement restored activity to normal levels. In sedentary animals, estrogen deprivation (ovariectomy) decreased baseline BDNF mRNA and protein, which were restored by estrogen replacement. Despite reduced activity levels in the ovariectomized condition, exercise increased BDNF mRNA levels in the hippocampus after short‐term (3 weeks) estrogen deprivation. However, long‐term estrogen‐deprivation blunted the exercise effect. After 7 weeks of estrogen deprivation, exercise alone no longer affected either BDNF mRNA or protein levels. However, exercise in combination with long‐term estrogen replacement increased BDNF protein above the effects of estrogen replacement alone. Interestingly, protein levels across all conditions correlated most closely with mRNA levels in the dentate gyrus, suggesting that expression of mRNA in this hippocampal region may be the major contributor to the hippocampal BDNF protein pool. The interaction of estrogen, physical activity and hippocampal BDNF is likely to be an important issue for maintenance of brain health, plasticity and general well‐being, particularly in women.
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Estrogen deprivation reduced BDNF gene expression in sedentary animals.
“estrogen deprivation reduced BDNF gene expression in sedentary animals.”
From Enrichment Effects on Adult Cognitive Development: Can the Functional Capacity of Older Adults Be Preserved and Enhanced? (2008) · cites this paper as Berchtold, Kesslak, Pike, Adlard, and Cotman (2001)
Estradiol administration restored estrogen to presurgical levels and increased voluntary running in ovariectomized rats.
“the administration of estradiol increased estrogen to levels observed prior to surgery, and it increased voluntary running.”
From Enrichment Effects on Adult Cognitive Development: Can the Functional Capacity of Older Adults Be Preserved and Enhanced? (2008) · cites this paper as Berchtold, Kesslak, Pike, Adlard, and Cotman (2001)
Five days of exercise restored BDNF levels to presurgical baseline in animals estrogen-deprived for three weeks.
“5 days of exercise increased BDNF levels to that of presurgical baseline in animals that had been estrogen deprived for 3 weeks.”
From Enrichment Effects on Adult Cognitive Development: Can the Functional Capacity of Older Adults Be Preserved and Enhanced? (2008) · cites this paper as Berchtold, Kesslak, Pike, Adlard, and Cotman (2001)
In ovariectomized adult female rats, voluntary wheel running was lower than in sham-operated controls.
“voluntary wheel running was reduced in the ovariectmized rats but not in the control (sham-operated) rats.”
From Enrichment Effects on Adult Cognitive Development: Can the Functional Capacity of Older Adults Be Preserved and Enhanced? (2008) · cites this paper as Berchtold, Kesslak, Pike, Adlard, and Cotman (2001)
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- Authors
- Berchtold, N. C., Kesslak, J. P., Pike, C. J., Adlard, P. A., & Cotman, C. W.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- Berchtold, Nicole C.
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2001-12
- Volume
- 14
- Issue
- 12
- Pages
- 1992-2002
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2046850163
- Cited by
- 329
- References
- 7
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 10 · 2023: 4 · 2022: 9 · 2021: 12 · 2020: 6 · 2019: 15 · 2018: 7 · 2017: 22 · 2016: 15 · 2015: 16 · 2014: 19 · 2013: 17 · 2012: 25
- FWCI
- 4.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ag013880-03)
- University of California, Irvine
- National Institute on Aging (AG13880, R01 AG 13411-04, AG 15961, R01AG013411)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- estrogen, physical activity, brain-derived neurotrophic factor, hippocampus, ovariectomy, estrogen replacement therapy, voluntary physical activity, dentate gyrus, mRNA-protein correlation, neuroplasticity
- MeSH terms
- Aging, Animals, Enzyme-Linked Immunosorbent Assay, Estrogens, Female, Gene Expression Regulation, Hippocampus, Menopause, Motor Activity, Neurons, Physical Conditioning, Animal, RNA, Messenger, Time Factors, Up-Regulation, Estrogen Replacement Therapy, Rats, Sprague-Dawley, Brain-Derived Neurotrophic Factor, Rats
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