Affiliation:
1. Department of Physiology Shiraz University of Medical Sciences Shiraz Iran
2. Histomorphometry and Stereology Research Centre Shiraz University of Medical Sciences Shiraz Iran
3. Clinical Neurology Research Centre Shiraz University of Medical Sciences Shiraz Iran
4. Stem Cells Technology Research Center Shiraz University of Medical Sciences Shiraz Iran
5. Shiraz Institute of Stem Cell and Regenerative Medicine Shiraz University of Medical Sciences Shiraz Iran
6. Shiraz Nephro‐Urology Research Center Shiraz University of Medical Sciences Shiraz Iran
Abstract
AbstractIntroductionVascular 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.Material and methodsThe 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.ResultsThe 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.ConclusionThe 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.