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

Exp Gerontol. 2018 Nov:113:209-217. doi: 10.1016/j.exger.2018.10.005. Epub 2018 Oct 7.

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.

Keywords: Aging; DNA damage; Histone deacetylases; Sodium butyrate; d-galactose.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / drug effects*
  • Animals
  • Brain / drug effects
  • Butyric Acid / pharmacology*
  • DNA Damage / drug effects
  • Disease Models, Animal
  • Galactose / pharmacology*
  • Histone Deacetylase Inhibitors / pharmacology*
  • Male
  • Maze Learning / drug effects
  • Memory / drug effects*
  • Rats
  • Rats, Wistar

Substances

  • Histone Deacetylase Inhibitors
  • Butyric Acid
  • Galactose