Shi Jing, Ma Yuxin, Zheng Meige, Ruan Zhigang, Liu Jing, Tian Sumin, Zhang Dexing, He Xinhong, Li Guoying
Department of Anatomy, Histology and Embryology, Basic Medical College, Guangdong Pharmaceutical University, Guangzhou, China.
Toxicol Ind Health. 2012 Feb;28(1):10-20. doi: 10.1177/0748233711401264. Epub 2011 Mar 28.
Occupational exposure and experimental intoxication of acrylamide (ACR) can produce skeletal muscle weakness and ataxia. In this study, we tested whether ACR would affect cerebellar function through the regulation of gamma-aminobutyric acid (GABA) and glial fibrillary acidic protein (GFAP) expression in cerebellum. Weaning male Sprague-Dawley rats were gavaged with ACR (5, 15, 30 mg/kg, 5 days per week) or saline for 4 weeks. Effects of ACR on the cerebellum were observed. For the 5 mg/kg group, no obvious change was observed, whereas moderate and severe ataxia were observed in the 15 mg/kg and 30 mg/kg groups, respectively. For the 15 mg/kg and 30 mg/kg groups, cerebellum concentrations of glutamate and GABA were dose-dependently decreased and increased, respectively. Moreover, the expression of GABA, the GABAergic presynaptic marker glutamate acid decarboxylase-65 (GAD65) and GFAP were significantly increased in those 2 groups. The results suggested that weaning rats were sensitive to ACR and that the toxic effects of ACR on the cerebellum may be associated with the increased expression of GABA and reactive astrocytes hypertrophy.
职业性接触丙烯酰胺（ACR）以及对其进行实验性中毒会导致骨骼肌无力和共济失调。在本研究中，我们测试了ACR是否会通过调节小脑γ-氨基丁酸（GABA）和胶质纤维酸性蛋白（GFAP）的表达来影响小脑功能。将断乳雄性斯普拉格-道利大鼠用ACR（5、15、30毫克/千克，每周5天）或生理盐水灌胃4周。观察ACR对小脑的影响。对于5毫克/千克组，未观察到明显变化，而在15毫克/千克和30毫克/千克组中分别观察到中度和重度共济失调。对于15毫克/千克和30毫克/千克组，小脑谷氨酸和GABA浓度分别呈剂量依赖性降低和升高。此外，这两组中GABA、GABA能突触前标志物谷氨酸脱羧酶-65（GAD65）和GFAP的表达均显著增加。结果表明，断乳大鼠对ACR敏感，ACR对小脑的毒性作用可能与GABA表达增加和反应性星形胶质细胞肥大有关。
