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.
J Alzheimers Dis. 2012;30(3):585-94. doi: 10.3233/JAD-2012-111946.
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.
农药广泛应用于农业，流行病学研究表明，农药暴露是阿尔茨海默病（AD）的一个风险因素，但机制尚不清楚。在这里，我们研究了农药暴露对大鼠认知能力和潜在机制的影响。溴氰菊酯和呋喃丹分别通过灌胃每天给大鼠给药一次，连续 28 天。我们发现，农药暴露诱导空间学习和记忆缺陷，同时减少 N-甲基-D-天冬氨酸受体 1、突触小体和突触素 I，所有这些都是与记忆相关的突触蛋白。农药暴露还诱导 AD 相关磷酸化位点的 tau 过度磷酸化，同时激活糖原合酶激酶-3β和抑制蛋白磷酸酶-2A。此外，在给予这些农药后，观察到海马和皮质中的神经元丢失。这些结果表明，农药暴露可诱导大鼠出现类似 AD 的病理学和认知异常。
