Ghobadi Mojtaba, Akbari Somayeh, Bayat Mahnaz, Moosavi Seyed Mostafa Shid, Salehi Mohammad Saied, Pandamooz Sareh, Azarpira Negar, Afshari Afsoon, Hooshmandi Etrat, Haghani Masoud
Department of Physiology, Shiraz University of Medical Sciences, Shiraz, Iran.
Histomorphometry and Stereology Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran.
Brain Behav. 2024 Jan;14(1):e3351. doi: 10.1002/brb3.3351.
Vascular dementia (VaD) is a common type of dementia. The aim of this study was to investigate the cellular and molecular mechanism of conditioned medium (CM) in VaD.
The rats were divided into four groups of control (n = 9), sham-operation (n = 10), VaD with vehicle (n = 9), and VaD with CM (n = 12) that received CM on days 4, 14, and 24 after 2VO. Before sacrificing the rats, cognitive performance was assessed through the open-field (OP), passive-avoidance, and Morris-water maze. The field-potential recording was used to investigate basal synaptic transmission (BST) and long-term potentiation (LTP). Subsequently, the hippocampus was dissected, and real-time PCR was used to quantify the expression levels of β1-catenin, insulin-like growth factor-1 (IGF-1), transforming growth factor-beta (TGF-β), glycogen synthase kinase-3β (GSK-3β), postsynaptic density protein 95 (PSD-95), and NR2B genes.
The results indicated impaired performance in behavioral tests in 2VO rats, coupled with reductions in BST and LTP induction. The expression levels of β1-catenin, IGF-1, PSD-95, and TGF-β genes decreased, whereas NR2B and GSK-3β expression increased. Treatment with CM restores the expression of PSD-95 and GSK-3β as well as fear-memory, spatial learning, and grooming number without a positive effect on memory retrieval, time spent on the periphery and center of OP. The BST recovered upon administration of CM but, the LTP induction was still impaired.
The recovery of BST in VaD rats appears to be the most important outcome of this study which is caused by the improvement of gene expression and leads to the restoration of fear memory.
血管性痴呆(VaD)是一种常见的痴呆类型。本研究的目的是探讨条件培养基(CM)在VaD中的细胞和分子机制。
将大鼠分为四组,即对照组(n = 9)、假手术组(n = 10)、VaD模型+赋形剂组(n = 9)和VaD模型+CM组(n = 12),后者在双侧颈总动脉永久性闭塞(2VO)后第4、14和24天接受CM治疗。在处死大鼠前,通过旷场试验(OP)、被动回避试验和莫里斯水迷宫评估认知能力。采用场电位记录法研究基础突触传递(BST)和长时程增强(LTP)。随后,解剖海马体,采用实时定量聚合酶链反应(PCR)定量β-连环蛋白1(β1-catenin)、胰岛素样生长因子-1(IGF-1)、转化生长因子-β(TGF-β)、糖原合酶激酶-3β(GSK-3β)、突触后致密蛋白95(PSD-95)和NR2B基因的表达水平。
结果表明,2VO大鼠行为学测试表现受损,同时BST和LTP诱导降低。β1-catenin基因、IGF-1基因、PSD-95基因和TGF-β基因表达水平降低,而NR2B基因和GSK-3β基因表达增加。CM治疗可恢复PSD-95基因和GSK-3β基因的表达以及恐惧记忆、空间学习和理毛次数,但对记忆提取、在旷场试验外周和中心停留时间无积极影响。给予CM后BST恢复,但LTP诱导仍受损。
VaD大鼠BST的恢复似乎是本研究的最重要结果,这是由基因表达改善引起的,并导致恐惧记忆的恢复。