Effect of Young Plasma Therapy on Cognition, Oxidative Stress, miRNA-134, BDNF, CREB, and SIRT-1 Expressions and Neuronal Survey in the Hippocampus of Aged Ovariectomized Rats with Alzheimer’s

Abstract

Menopause may increase the risk of Alzheimer’s disease (AD) dementia. This study aimed to use young plasma therapy (YPT) to improve dementia caused by AD in aged ovariectomized rats. Female Wistar rats were used in the following groups: (a) young (CY) (180–200 g, 2–3 months, n = 10) and (b) old groups (250–350 g, 22–24 months, n = 60). The old rats were randomly assigned to six sub-groups: (1) control, (2) sham, (3) ovariectomized group (OVX), (4) OVX + Alzheimer disease (OVX + AD), (5) OVX + AD+ 17β-Estradiol (OVX + AD + E), and (6) OVX + AD + young plasma (OVX + AD + YP). Cognitive behaviors were evaluated using NOR, MWM, and PAL tests. MiR-134a, SIRT-1, CREB, and BDNF expressions were measured using real-time PCR and western blot, respectively. Oxidative stress in hippocampal tissue was assayed using ELISA kits. OVX and AD caused significant cognitive impairment (p < 0.001), up-regulated miR-134a (p < 0.001), down-regulated SIRT-1, CREB, and BDNF protein expression (p < 0.001), and decreased antioxidant marker levels (p < 0.001) compared to the sham group. YPT significantly restored miR-134a (p < 0.001), SIRT-1 (p < 0.001), CREB (p < 0.001), and BDNF (p < 0.001) protein expression in OVX + AD rats. YPT, as much as or more than estrogen therapy (ERT), significantly improved oxidative stress and down-regulated miR-134a expression and the up-regulation of SIRT-1, CREB, and BDNF proteins in OVX + AD rats (p < 0.001). YPT significantly improved histological alteration compared to the OVX + AD group (p < 0.001). As a non-pharmacological treatment, YPT can improve the expression of miR-134a and SIRT-1, CREB, and BDNF proteins as much as or more than estrogen therapy, ameliorating AD-induced dementia in aged OVX rats.