Madadi Soheila, Katebi Majid, Eftekharzadeh Mina, Mehdipour Ahmad, Pourheydar Bagher, Mehdizadeh Mehdi
Department of Anatomy, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran.
Department of Anatomy, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Basic Clin Neurosci. 2019 Nov-Dec;10(6):567-577. doi: 10.32598/BCN.9.10.90. Epub 2019 Nov 1.
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.
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.
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.
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.
三甲基氯化锡（TMT）是一种神经毒素，可杀死神经系统中的神经元并激活星形胶质细胞。这种神经毒素主要损害海马神经元。注射TMT后，动物会出现攻击和多动等行为变化，同时空间和学习记忆受损。因此，TMT是神经退行性变实验模型的合适工具。本研究旨在确定骨髓间充质干细胞（BM-MSCs）对TMT暴露损伤的大鼠海马的缓解作用。
我们将28只雄性Wistar大鼠分为以下几组：对照组、模型组、溶剂组和治疗组。这些组腹腔注射8mg/kg的TMT。一周后，将干细胞立体定向注射到右侧大鼠海马的CA1区。细胞移植6周后，通过莫里斯水迷宫（MWM）试验测定空间记忆。最后，对大鼠的大脑进行灌注并用甲酚紫染色，以确定海马角回（CA1）区的细胞数量。我们通过蛋白质印迹法评估右侧海马中胶质纤维酸性蛋白（GFAP）和神经元特异性核蛋白（NeuN）的表达。
MWM试验表明，与模型组和溶剂组相比，治疗组在目标象限的游动距离显著更长（P<0.05）。基于细胞计数（尼氏染色）结果，与模型组和溶剂组相比，治疗组的细胞数量增加（P<0.05）。蛋白质印迹结果显示，与对照组相比，模型组、溶剂组和治疗组中GFAP和NeuN蛋白上调。
注射BM-MSCs可能通过增加锥体细胞数量和改善记忆，导致TMT诱导的神经毒性在行为和组织学上得到改善。
