Trimethyltin chloride (TMT) is a by-product in the synthesis of organotin, a plastic stabilizer. With the rapid development of industry, the occupational hazards caused by TMT cannot be ignored. TMT is a typical neurotoxicant, which mainly damages the limbic system and brainstem of the nervous system. Previous studies have demonstrated that the neurotoxicity induced by TMT is linked to the inhibition of energy metabolism, but the underlying mechanism remains elusive. In order to investigate the mechanism of TMT-induced inhibition of energy metabolism, C57BL/6 male mice were administered by IP injection in different TMT doses (0 mg/kg, 1.00 mg/kg, 2.15 mg/kg and 4.64 mg/kg) and times (1d, 3d and 6d), and then the changes of superoxide dismutase (SOD) activity, malondialdehyde (MDA) level and Na+-K+-ATPase activity in cerebral cortex, cerebellum, hippocampus, pons, medulla oblongata of mice, the expressions of Na+-K+-ATPase protein, AMP-activated protein kinase (AMPK), phosphorylated AMP-activated protein kinase(p-AMPK)and peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α) in hippocampus and medulla oblongata were measured; the effects of TMT on the viability, the activity of SOD, glutathione (GSH) and Na+-K+-ATPase, MDA level, and the expression of PGC-1α and Na+-K+-ATPase protein in N2a cells were measured by different TMT doses and times, in order to verify the experiments in vivo. Our results found that most of the mice showed depression, tremor, epilepsy, spasm and other symptoms after TMT exposure. Moreover, with the increase of TMT dose, the activity of Na+-K+-ATPase and the expressions of AMPK protein in the hippocampus and medulla oblongata of mice decreased, and the expressions of p-AMPK protein increased. Peroxidative damage was evident in hippocampus, medulla oblongata of mice and N2a cells, and the expression of PGC-1α and Na+-K+-ATPase protein was significantly down-regulated. Therefore, it is reasonable to believe that TMT-induced neurotoxic symptoms and inhibition of energy metabolism may be related to p-AMPK and down-regulation of PGC-1α in the hippocampus and medulla oblongata.

Trimethyltin chloride (TMT) is a stabilizer by-product in the process of manufacturing plastic, which is a kind of very strong toxic substance, and has acute, cumulative and chronic toxicity. TMT may cause bradycardia in patients with occupational poisoning, the mechanism of which has not been reported. This study explored the mechanism of TMT resulting in bradycardia of C57BL/6 mice. TMT was administered to mice to measure heart rate, serum succinate dehydrogenase (SDH) level, and myocardial Na+/K+-ATPase activity and expression. The effects of TMT on myocardial apoptosis were observed by changing the expressions of caspase-3, Bax and Bcl-2 in myocardium. It was found that the heart rate and SDH activity in serum of mice gradually decreased with the increase of TMT dose compared with the control group. The activity and the expression of Na+/K+-ATPase in the heart tissue of mice exposed to TMT was measured and gradually decreased with the increase of dose and time. We measured the expression of Bcl-2, Bax, caspase-3 and cleaved caspase-3 in the heart tissues of TMT exposed mice and found that the expressions of Bax, caspase-3 and cleaved caspase-3 increased and the expressions of Bcl-2 decreased in the heart tissues of the TMT-exposed mice at different doses. With the extension of TMT exposure time, the expression of Bax and caspase-3 increased and the expression of Bcl-2 decreased in the heart tissues of TMT exposed mice. Our findings suggest the mechanisms of TMT resulting in bradycardia may be associated with the inhibited activity and decreased content of Na+/K+-ATPase, thus further leading to the changes of Bcl-2, Bax, caspase-3 and cleaved caspase-3 in the mice\'s ventricular tissues.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.