Subchronic exposure to acrylamide caused behaviour disorders and related pathological and molecular changes in rat...

Acrylamide (ACR) is a neurotoxin with moderate acute toxicity. Significant level of ACR exists in diet and drinking water. Occupational exposure causes motor function impairment, but the underlying mechanisms remain poorly defined. This study aims to explore whether microtubule-associated protein tau phosphorylation, excessive activation of protein kinase RNA-like endoplasmic reticulum kinase (PERK) signaling pathway and BDNF decline are involved in cerebellar neuron lesions and motor dysfunction after subchronic ACR exposure. The present results displayed that ACR caused gait abnormality and hind foot splay in rats. The HE and Nissl staining results revealed that ACR exposure aggravated cerebellar neuron lesions especially in purkinje cell layer. ACR markedly increased tau phosphorylation at Ser262 and Ser396/404 and inhibited the level of phosphorylation of glycogen synthase kinase 3β (P-GSK3β) at Ser9. The PERK-eukaryotic initiation factor-2α (eIF2α)-activating transcription factor 4 (ATF4) pathway was activated to promote CHOP expression and then to accelerate neuron lesions. Furthermore, ACR significantly decreased P-CREB at Ser133 and BDNF expression, which might be related to the inhibition of upstream signals from extracellular signal-related kinase (ERK) and protein kinase B (Akt). This work helps to elucidate the underlying mechanisms of ACR-induced neurotoxicity and present a potential target for prevention against the neurotoxicity.