1- Department of Anatomy, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran.
2- Department of Anatomy, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
3- Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
4- Department of Tissue Engineering, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
5- Neurophysiology Research Center, Department of Anatomy, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
6- Cellular and Molecular Research Center, Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Abstract:
Introduction: Trimethyltin Chloride (TMT) is a neurotoxin that can kill neurons in the nervous system and activate astrocytes. This neurotoxin mainly damages the hippocampal neurons. After TMT injection, behavioral changes such as aggression and hyperactivity have been reported in animals along with impaired spatial and learning memory. Hence, TMT is a suitable tool for an experimental model of neurodegeneration. The present study aims to determine the palliative effects of Bone Marrow-derived Mesenchymal Stem Cells (BM-MSCs) on the hippocampi of rats damaged from TMT exposure.
Methods: We assigned 28 male Wistar rats to the following groups: control, model, vehicle, and treatment. The groups received Intraperitoneal (IP) injections of 8 mg/kg TMT. After one week, stem cells were stereotactically injected into the CA1 of the right rats’ hippocampi. Spatial memory was determined by the Morris Water Maze (MWM) test 6 weeks after cell transplantation. Finally, the rats’ brains were perfused and stained by cresyl violet to determine the numbers of cells in the Cornus Ammonis (CA1) section of the hippocampus. We assessed the expressions of Glial Fibrillary Acidic Protein (GFAP) and Neuronal-specific Nuclear (NeuN) proteins in the right hippocampus by Western blot.
Results: The MWM test showed that the treatment group had significantly higher traveled distances in the target quarter compared with the model and vehicle groups (P<0.05). Based on the result of cell count (Nissl staining), the number of cells increased in the treatment group compared with the model and vehicle groups (P<0.05). Western blot results showed up-regulation of GFAP and NeuN proteins in the model, vehicle, and treatment groups compared with the control group.
Conclusion: Injection of BM-MSCs may lead to a behavioral and histological improvement in TMT-induced neurotoxicity by increasing the number of pyramidal neurons and improving memory.
Full-Text [PDF 1395 kb]
| |
Full-Text (HTML)
●The transplantation of Bone Marrow-derived Mesenchymal Stem Cells (BM-MSCs) increased the number of pyramidal neurons in the damaged hippocampus.
●The BM-MSCs transplantation alleviated impaired memory caused by trimethyltin chloride exposure.
●The transplantation of BM-MSCs increased neuronal specific nuclear protein expression and decreased the expression of the glial fibrillary acidic protein.
Plain Language Summary
The hippocampus is a key area in the cortex of the brain. It is associated with memory and learning and has a vital role in the formation of new memory, spatial analysis, as well as integration and transfer of information from short-term to long-term memory. Despite the vital role of the hippocampus in memory and spatial learning, this organ is unprotected and very sensitive and vulnerable to injuries. The hippocampus gets injured by hypoxia, encephalitis, infection, Alzheimer disease, stroke, ischemia, and especially brain trauma. In the case of brain infections, in the limbic, amygdala, and hippocampal systems, the behavioral changes are observed due to short-term memory and spatial recognition impairment. Studies have shown that the mammalian hippocampus has neurogenesis ability throughout life. However, it cannot overcome hippocampus damages. Considering the high sensitivity of the hippocampal tissue and its essential role in memory and learning, it is very important to find a way to reduce its damage and treat it after injuries. Trimethyltin chloride (TMT) is a neurotoxin that can kill neurons in the nervous system. This neurotoxin mainly damages the hippocampal neurons. Hence, TMT is a suitable tool for an experimental model of neurodegeneration. Today, stem cells are a suitable treatment method for the improvement of nervous system disease. So that following transplantation of stem cells, neuron regeneration occurs in damaged regions. The present study showed that using bone marrow mesenchymal stem cells decreases hippocampal lesions by increasing the number of pyramidal neurons, improving behavioral performance and memory, and reducing cognitive deficits.
Type of Study:
Original |
Subject:
Behavioral Neuroscience Received: 2018/04/29 | Accepted: 2019/01/8 | Published: 2019/11/1