Habibi Parisa, Shahidi Siamak, Khajvand-Abedini Maryam, Shahabi Zahra, Ahmadiasl Nasser, Alipour Mohammad Reza, Ramezani Mahdi, Komaki Alireza
Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan 651783873, Iran.
Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran 1461884513, Iran.
Brain Sci. 2024 Jun 28;14(7):656. doi: 10.3390/brainsci14070656.
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 ( 0.001), up-regulated miR-134a ( 0.001), down-regulated SIRT-1, CREB, and BDNF protein expression ( 0.001), and decreased antioxidant marker levels ( 0.001) compared to the sham group. YPT significantly restored miR-134a ( 0.001), SIRT-1 ( 0.001), CREB ( 0.001), and BDNF ( 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 ( 0.001). YPT significantly improved histological alteration compared to the OVX + AD group ( 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.
绝经可能会增加患阿尔茨海默病(AD)性痴呆的风险。本研究旨在采用年轻血浆疗法(YPT)改善老年去卵巢大鼠由AD引起的痴呆。将雌性Wistar大鼠分为以下几组:(a)年轻组(CY)(180 - 200克,2 - 3个月,n = 10)和(b)老年组(250 - 350克,22 - 24个月,n = 60)。老年大鼠被随机分为六个亚组:(1)对照组,(2)假手术组,(3)去卵巢组(OVX),(4)去卵巢 + 阿尔茨海默病组(OVX + AD),(5)去卵巢 + AD + 17β - 雌二醇组(OVX + AD + E),以及(6)去卵巢 + AD + 年轻血浆组(OVX + AD + YP)。使用新颖物体识别测试(NOR)、 Morris水迷宫测试(MWM)和平台交替测试(PAL)评估认知行为。分别使用实时聚合酶链反应(PCR)和蛋白质免疫印迹法测量miR - 134a、沉默调节蛋白1(SIRT - 1)、环磷腺苷效应元件结合蛋白(CREB)和脑源性神经营养因子(BDNF)的表达。使用酶联免疫吸附测定试剂盒(ELISA)检测海马组织中的氧化应激。与假手术组相比,去卵巢和AD导致显著的认知障碍(P < 0.001),miR - 134a上调(P < 0.001),SIRT - 1、CREB和BDNF蛋白表达下调(P < 0.001),抗氧化标志物水平降低(P < 0.001)。YPT显著恢复了OVX + AD大鼠中miR - 134a(P < 0.001)、SIRT - 1(P < 0.001)、CREB(P < 0.001)和BDNF(P < 0.001)的蛋白表达。YPT在改善氧化应激、下调miR - 134a表达以及上调OVX + AD大鼠中SIRT - 1、CREB和BDNF蛋白方面,与雌激素替代疗法(ERT)相当或更优(P < 0.001)。与OVX + AD组相比,YPT显著改善了组织学改变(P < 0.001)。作为一种非药物治疗方法,YPT在改善miR - 134a和SIRT - 1、CREB及BDNF蛋白表达方面与雌激素疗法相当或更优,可改善老年去卵巢大鼠中AD诱导的痴呆。