| Objectves1-Bromopropane (1-BP) was recently introduced as an alternative cleaner to1,1,1-trichloroethane, chlorofluorocarbons and suspected carcinogens such as trichloroethylene, methylene chloride, which have the potential to destroy the ozone layer. The neurotoxic effects of this agent have been described in humans and experimental animals. It affected the function of the central nervous system and caused disorders of peripheral nerves. But its mechanism of neurotoxicity in humans is not well understood. In this study, the rats were treated with different dosage of1-BP by gavage, and the Morris water maze (MWM) test was applied to evaluate the learning-memory function in rats. After the MWM test, rats were sacrificed, the cerebral cortex and hippocampus quickly dissected and homogenized in ice bath. The supernatant of their homogenate was collected to detect the changes of the central cholinergic system and the oxidation and anti-oxidation system respectively. The aim of our study is to illustrate that the dysfunction of the central cholinergic system and the antioxidative system are attributed to the damage of cognitve function.MethodAfter3days acclimation,48Male Wistar rats were randomly divided into four groups with12in each, i.e.1-BP low-dose group (200mg/kg), medium-dose group (400mg/kg), high-dose group (800mg/kg) and control group. Animals in each group were given in accordance with their own dosage for7days, and then the Morris water maze (MWM) test was applied to evaluate the learning-memory function in rats. The escape latency, total distance in the place navigation trial, and the percentages of the time spent in the platform quadrant, the number of platform crossing in set time of spatial probe trial were recorded respectively.After the MWM test, rats were sacrificed, the cerebral cortex and hippocampus quickly dissected and homogenized in ice bath. The supernatant of their homogenate was collected to detect the activity of Acetylcholine esterase (AChE), Choline acetyltransferase (ChAT), Glutathione reductase (GR), Glutathione Peroxidase (GSH-PX) and the content of Glutathione (GSH), Malondialdehyde (MDA), Total Hydrosulfide (-SH) and Acetylcholine (ACh) both in Cortex and the hippocampus. The4-HNE and MDA ptotein adducts were both detected by western blotting.2of rats in each group were fixed in vivo with4%paraformaldehyde solution, and the rats’ brains were dissected. After paraffin embedding, serial sections were done at intervals of5μm. then, tissues sections were stained with hematoxylin-eosin to observe the structure of neuron in cortex and the hippocampus.Results1. The results of the MWMCompared with control group, the latency and total swim distance of rats in medium and high-dose groups were prolonged significantly (p<0.05) in place navigation test, the efficiency of searching strategy was lower (p<0.05) as well. In spatial probe test, the number of crossing the platform of rats in three dose groups decreased evidently (p<0.05,p<0.01). The cortical AChE activity of rats in medium and high-dose group was significantly higher than that of control and low-dose group (p<0.05,p<0.01). The AChE activity in rat hippocampus of high-dose group also increased (p<0.05).The cortical ChAT activity tended to decrease after treating1-BP but there was no statistically difference compared to the control group (p>0.05). In the hippocampus, there was no difference of ChAT activity among the groups (p>0.05). 2. The changes of Biochemical indicatorsIn our study, the cortical AChE and GSH-PX activity of rats in medium and high-dose group was higher than that of control and low-dose group (p<0.05). Also the activity of AChE was increased in the hippocampus (P<0.05), but there was no obvious difference in the four groups about ChAT. The contents of MDA in the cortex increased appearently (P<0.05,P<0.01). In addition, the contents of GSH, Total Hydrosulfide and the activity of GR all reduced significantly (P<0.05,P<0.01)3. Western Blotting resultsCompared to comtrol group, densitometric analysis showed that the express of4-HNE protein adducts in the brain of the three dose-groups increased by42%(p<0.05),44%and77%in the middle and high-group (p<0.01). The content of MDA modified proteins in the brain in the three dose-groups were all increased, but only the high-dose group had a significant change by an increment of86%(p<0.05).Conclusion1.1-BP exposure could significantly damage the learning-memory function in rats.2. The disfunction of the rats’learning and memory might be partly ascribed to the changes of the central cholinergic system induced by1-BP.3. The disturbance of oxidation and antioxidation system in rat’s brain might attribute to the injury of the cognitive function of rat exposure to1-BP. |
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