Affiliations: Department of Pathophysiology, Key Laboratory of Chinese Ministry of Education for Neurological Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
Correspondence:
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Correspondence to: Gong-Ping Liu, Department of Pathophysiology, Key Laboratory of Neurological Diseases of Education Committee of China, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, 430030 Wuhan, PR China. Tel.: +86 27 83692625; Fax: +86 02783692625; E-mail: liugp111@mail.hust.edu.cn.
Note: [1] These authors contributed equally.
Abstract: Pesticides are widely used in agriculture, and epidemiological studies suggest that pesticide exposure is a risk factor for Alzheimer's disease (AD), but the mechanisms are elusive. Here, we studied the effects of pesticide exposure on the cognitive ability and the underlying mechanisms in rats. Deltamethrin and carbofuran were administered respectively into the rats once a day for 28 days by gavage. We found that pesticide exposure induced spatial learning and memory deficits with a simultaneous decrease of N-methyl-D-aspartate receptor 1, synaptophysin, and synapsin I, all of which are memory-related synaptic proteins. Pesticide exposure also induced tau hyperphosphorylation at multiple AD-related phosphorylation sites with activation of glycogen synthase kinase-3β and inhibition of protein phosphatase-2A. Additionally, neuron loss in the hippocampus and cortex was observed upon administration of the pesticides. These results indicate that the pesticides exposure could induce AD-like pathology and cognitive abnormality in rats.
Keywords: Alzheimer's disease, glycogen synthase kinase-3β, pesticides, protein phosphatase-2A, tau
