Gens PSD‐95 and GSK‐3β expression improved by hair follicular stem cells‐conditioned medium enhances synaptic transmission and cognitive abilities in the rat model of vascular dementia

Abstract

Abstract Introduction 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. Material and methods 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. Results 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. Conclusion 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.

Keywords

• conditioned medium
• long‐term potentiation
• memory
• synaptic transmission
• vascular dementia