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

• Published in: Brain and behavior 2024-01, Vol.14 (1), p.e3351-n/a
• Main Authors: Ghobadi, Mojtaba, Akbari, Somayeh, Bayat, Mahnaz, Moosavi, Seyed Mostafa Shid, Salehi, Mohammad Saied, Pandamooz, Sareh, Azarpira, Negar, Afshari, Afsoon, Hooshmandi, Etrat, Haghani, Masoud
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Animal cognition; Animals; Cardiovascular disease; Catenins - metabolism; Catenins - pharmacology; Cognition; Cognitive ability; conditioned medium; Culture Media, Conditioned - metabolism; Culture Media, Conditioned - pharmacology; Dementia; Dementia, Vascular; Disks Large Homolog 4 Protein; Glycogen Synthase Kinase 3 beta - metabolism; Growth factors; Hippocampus - metabolism; Insulin-Like Growth Factor I - metabolism; Insulin-Like Growth Factor I - pharmacology; Kinases; long‐term potentiation; Maze Learning; Memory; Original; Proteins; Rats; Rats, Sprague-Dawley; Stem cell transplantation; Stem Cells - metabolism; Surgery; Synaptic Transmission; Transforming Growth Factor beta - metabolism; vascular dementia
• ISSN: 2162-3279; 2162-3279
• DOI: 10.1002/brb3.3351

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. Vascular dementia (VaD) is a common type of dementia that occurs when there is damage to the blood vessels in the brain. While there is no cure for VaD, treatment focuses on managing underlying conditions and controlling risk factors. In recent years, there has been an increasing interest in the use of conditioned medium (CM) for the treatment of degenerative diseases. Thus, this study aimed to investigate the cellular and molecular mechanism of CM administration in VaD Our data indicated that treatment with CM led to the recovery of basal synaptic transmission and cognitive performance in VaD rats which is probably caused by the improvement of gene expression.