Effect of long-term exposure to acrylamide on endoplasmic reticulum stress and autophagy in rat cerebellum.

Abstract

Acrylamide (ACR) is a widely used chemical compound that has neurotoxicity in human, but whether ACR could impair the cerebellum and the related mechanism were still unknown. This study aimed to observe the changes in behavioral performance and cerebellar morphology caused by chronic ACR exposure, and to evaluate its influence on apoptosis, endoplasmic reticulum stress (ERS) and autophagy. Rats were treated with 0, 0.5 and 5\xa0mg/kg ACR by drinking water for 12 months. Results showed that 5\xa0mg/kg ACR treatment damaged the gait, balance ability, hindlimb muscle strength and motor coordination ability of rats. The results of hematoxylin and eosin and Nissl staining indicated that ACR impaired the structures of all three layers of the cerebellum, especially the Purkinje cell layer, showing abnormal morphology with nucleus condensation and pyknosis. Accumulation of autophagosomes, dilated endoplasmic reticulum and swollen mitochondria were observed in neurons under transmission electron microscopy. The enhanced apoptotic rates and the increased Bax expression indicated the elevated level of apoptosis. The results of Western blot showed that ACR treatment elevated protein levels of Beclin1, LC3-II/LC3-I, p-PERK/t-PERK, ATF4 and CHOP, indicating the initiation of autophagy, the activation of PERK pathway in ERS. This work helps to demonstrate the ACR neurotoxicity on cerebellum under chronic treatment and its underlying mechanism.