Laboratory of Experimental Neurology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.
Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.
Exp Gerontol. 2018 Nov;113:209-217. doi: 10.1016/j.exger.2018.10.005. Epub 2018 Oct 7.
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.
衰老是一个复杂的生物学过程。表观遗传改变与衰老和记忆衰退都有关。其中包括组蛋白乙酰化，它可能在衰老中起关键作用。因此，本研究的目的是标准化 D-半乳糖（D-gal）的动物模型，并评估丁酸钠（SB）作为组蛋白去乙酰化酶抑制剂对记忆、组蛋白去乙酰化酶（HDACs）的调节以及 2、6 或 16 个月大的 Wistar 大鼠的 DNA 损伤的影响，这些大鼠接受 D-gal 的给药。为了帮助选择诱导衰老模型的最佳 D-gal 剂量，我们进行了剂量反应曲线（100、200 或 300mg/kg）。D-gal 以口服方式给予 2 个月大的大鼠，持续 30 天。之后，D-gal（200mg/kg）或水给予 2、6 或 16 个月大的大鼠，持续 30 天。在第 24 天，开始用 SB（600mg/kg）腹膜内给药，持续 7 天。SB 能够逆转 D-gal 对 2 个月和 6 个月大的大鼠习惯记忆损伤，但不能逆转 16 个月大的动物的损伤。此外，SB 能够逆转 16 个月大的动物的自然衰老引起的损伤。在抑制性回避任务中，SB 改善了 D-gal 对 2、6 和 16 个月大的动物的损伤，对 16 个月大的大鼠的自然衰老的影响也有相同的结果。此外，D-gal 导致 16 个月大的动物的 HDACs 活性水平升高，而 SB 能够逆转前额叶皮层和海马中的这种作用。16 个月大的动物外周血中 DNA 损伤的频率增加，而 SB 能够减少这种损伤。此外，D-gal 导致 2 个月和 6 个月大的动物的 DNA 损伤指数和频率增加，而 SB 的治疗能够预防这种损伤。因此，本研究显示了 SB 对大鼠自然衰老和 D-gal 诱导衰老的记忆的保护作用。因此，本研究为 SB 在衰老中的应用提供了新的发现。
