Sodium butyrate improves memory and modulates the activity of histone deacetylases in aged rats after the administration of d-galactose

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...

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Published in:Experimental gerontology 2018-11, Vol.113, p.209-217
Main Authors: Garcez, Michelle Lima, de Carvalho, Carlos Alberto, Mina, Francielle, Bellettini-Santos, Tatiani, Schiavo, Gustavo Luis, da Silva, Sabrina, Campos, Ana Carolina Brunatto Falchetti, Varela, Roger Bitencourt, Valvassori, Samira S., Damiani, Adriani Paganini, Longaretti, Luiza Martins, de Andrade, Vanessa Moraes, Budni, Josiane
Format: Article
Language:English
Subjects:
Aging
Aging - drug effects
Animals
Brain - drug effects
Butyric Acid - pharmacology
d-galactose
Disease Models, Animal
DNA damage
DNA Damage - drug effects
Galactose - pharmacology
Histone Deacetylase Inhibitors - pharmacology
Histone deacetylases
Male
Maze Learning - drug effects
Memory - drug effects
Rats
Rats, Wistar
Sodium butyrate
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Summary: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. •SB reversed habituation memory damage in the aged and/or in d-gal-induced animals.•SB reversed aversive memory damage in the aged and/or in d-gal-induced animals.•SB reduced HDACs activity increases caused by d-gal.•SB reduced frequency and rate of DNA damage caused by d-gal.
ISSN:0531-5565
1873-6815
DOI:10.1016/j.exger.2018.10.005