Журнал болезни Альцгеймера и паркинсонизма

Абстрактный

Docosahexaenoic Acid Protects against 1-Bromopropane Induced Cognitive Deficits in Rats involving in GSK-3β Activation and Oxidative Stress Inhibition

Junlin Yang, Hua Yuan, Lulu Jiang, Ying Guo, Zengjin Wang, Keqin Xie and Xiulan Zhao

A number of organic solvent are known to be neurotoxic substance, which can cause neurotoxicological effects in humans. 1-Bromopropane (1-BP) is an alternative to ozone-depleting solvent that widely used in industrial production. Occupational exposure to 1-BP becomes a major health concern due to its neurotoxicity displayed in animals and humans. Docosahexaenoic acid (DHA), long chain n-3 polyunsaturated fatty acids (PUFA) and the main component of fish oil, is essential for normal neurological development and displays potent neuroprotective capacity. Here we investigate the protective effects and underlying mechanisms of DHA against 1-BP-induced deficits of spatial learning and memory ability in rats. Cognitive performance was assessed by Morris Water Maze test (MWM). Neuronal injury was determined by Nissl staining and TUNEL staining. The apoptosis-related proteins, including cleaved caspase-3, Bcl-2 and Bax, and proteins modified by 4-hydroxy-2-nonenal (4-HNE) or acrolein, in the brain were determined by Western blot. The inactive glycogen synthase kinase-3β (GSK-3β) in the brain of rats was also detected by specific antibody. Exposure to 1-BP resulted in learning deficits and memory loss of rats, neuronal apoptosis in the hippocampus cornu ammonis 3 (CA3) and prefrontal cortex, accompanied with significant GSK-3β inhibition by phosphorylation. Importantly, we found that pre-treatment with DHA significantly improved MWM performances of rats intoxicated with 1-BP, as well as the abrogation of neuron loss, alleviation of redox unbalance and GSK-3β activation in the brain. Our findings suggested that DHA supplementation would be a promising intervention for the central neurotoxicity of 1-BP, which might be correlated with oxidative stress and GSK-3β inhibition.