Sodium butyrate improves memory and modulates the activity of histone deacetylases in aged rats after the administration of d-galactose
Abstract
Aging is a complex biological process. Epigenetic alterations have been related to both aging and memory decline. Included amongst these alterations is histone acetylation, which may play a crucial role in aging. Thus, the aims of the present study were to standardize the animal model of d-galactose (d-gal), and to evaluate the effects caused by sodium butyrate (SB), which is a histone deacetylase inhibitor on memory, the modulation of histone deacetylases (HDACs), and also DNA damage in 2, 6 or 16-month-old Wistar rats which were subjected to administrations of d-gal. To help choose the best dose of d-gal for the induction of the aging model, we performed a dose-response curve (100, 200 or 300 mg/kg). d-Gal was administered orally to the 2-month-old rats for a period of 30 days. After this, d-gal (200 mg/kg) or water were administered to the 2, 6 or 16-month-old rats for a period of 30 days. On the 24th day, treatment was started with SB (600 mg/kg) intraperitoneally, for a period of 7 days. SB was able to reverse the damage to habituation memory caused by d-gal in the 2 and 6-month-old rats, but was unable to reverse the damage in the 16 month-old animals. In addition, SB was able to reverse the damage caused by natural aging in the 16-month-old animals. In the inhibitory avoidance task, SB improved the damage caused by d-gal in the 2, 6 and 16-month-old animals and had the same result against the effects of natural aging in the 16-month-old rats. Moreover, d-gal caused an increase in the level of HDACs activity in the 16-month-old animals, and SB was able to reverse this effect in the frontal cortex and hippocampus. The 16-month-old animals showed an increase in the frequency of DNA damage in peripheral blood, and SB was able to reduce this damage. Moreover, d-gal caused an increase in the index and frequency of DNA damage in the 2 and 6-month-old animals, and treatment with SB was able to prevent this damage. Thus, the present study showed the protective effects of SB on the memory of naturally aged and d-gal induced aging in rats. Therefore, the present study shows new findings for the use of SB in aging.
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HDAC inhibition enhances long-term potentiation and contextual fear memory.
“These studies have reported an enhancement of long-term potentiation (LTP) and contextual fear memory induced by HDAC inhibition (124, 127, 136, 137), pointing out enteric SCFAs as a promising learning and memory modulators.”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [137]
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“Additionally, an excess of galactiol induces overproduction of reactive oxygen species (ROS), leading to damage to cells and tissues (Zhang et al., 2014; Yu et al., 2015; Shen et al., 2017).”
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The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication
Silva, Y. P., Bernardi, A., & Frozza, R. L. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00025 · Cited by 3,043 · see citing works
“Moreover, other studies have shown beneficial effects of butyrate and probiotic treatment on cognition and memory in a D-galactose model of aging, a condition known to correlate with AD occurrence and progression (137, 167).”
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- Authors
- Garcez, M. L., de Carvalho, C. A., Mina, F., Bellettini-Santos, T., Schiavo, G. L., da Silva, S., Campos, A. C. B. F., Varela, R. B., Valvassori, S. S., Damiani, A. P., Longaretti, L. M., de Andrade, V. M., & Budni, J.
- Affiliations
- Universidade do Extremo Sul Catarinense (BR)
- Corresponding author
- Budni, Josiane
- ORCID
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 2018-11
- Volume
- 113
- Pages
- 209-217
- ISSN
- 0531-5565 (ISSN-L)
- OpenAlex
- W2894969128
- Cited by
- 41
- References
- 6
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 7 · 2023: 4 · 2022: 4 · 2021: 5 · 2020: 5 · 2019: 2
- FWCI
- 1.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Gerontology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- CNPq (312184/2016-6)
- FAPESC
- UNESC
- CAPES
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Antioxidants, Aging, Portulaca oleracea
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- sodium butyrate, galactose, aging, memory impairment, histone deacetylase, histone deacetylase inhibition, DNA damage, epigenetic aging, passive avoidance, frontal cortex, hippocampus, age-related memory decline, animal models of aging, Wistar rats, dose-response curves
- MeSH terms
- Aging, Animals, Brain, Disease Models, Animal, DNA Damage, Galactose, Male, Memory, Rats, Wistar, Maze Learning, Butyric Acid, Rats, Histone Deacetylase Inhibitors
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