Taurine attenuates acrylamide-induced axonal and myelinated damage through the Akt/GSK3β-dependent pathway

Abstract

Acrylamide (ACR), formed during the Maillard reaction induced by high temperature in food processing, is one of the main causes of neurodegenerative diseases. Taurine, a free intracellular β-amino acid, is characterized by many functions, including antioxidation, anti-inflammatory, and neuroprotective properties. This promotes its application in the treatment of neurodegenerative diseases. In this study, the neuroprotective effects of taurine against ACR-induced neurotoxicity and the potential underlying mechanisms were explored. Rats were intoxicated with ACR and injected with taurine in different groups for totally 2 weeks between January and July 2017. Electron microscopic analysis was used to observe the changes in tissues of the rats. Meanwhile, the levels of proteins including p-Akt, p-GSK3β, SIM312, and MBP were detected by Western blot. Furthermore, the GSK3β phosphorylation in taurine-treated dorsal root ganglion (DRG) with ACR was examined in the presence of the Akt inhibitor, MK-2206. The analysis of behavioral performances and electron micrographs indicated that taurine treatment significantly attenuated the toxic manifestations induced by ACR and stimulated the growth of axons and the medullary sheath, which was associated with the activation of the Akt/GSK3β signaling pathway. Mechanistically, it was found that taurine activated GSK3β, leading to significant recovery of the damage in ACR-induced sciatic nerves. Furthermore, MK-2206, an inhibitor of Akt, was applied in DRG cells, suggesting that taurine-induced GSK3β phosphorylation was Akt dependent. Our findings demonstrated that taurine attenuated ACR-induced neuropathy in vivo, in an Akt/GSK3β-dependent manner. This confirmed the treatment with taurine to be a novel strategy against ACR-induced neurotoxicity.

Keywords: Akt/GSK3β-dependent pathway; acrylamide; axonal and myelinated damage; taurine.

Figure 1.

(a) Group assignments were drawn as a time sequence diagram. (b) Clinical performance of each group on day 14. Control group: rats received normal feeding; ACR group: rats were received ACR (50 mg/kg/day i.p.); ACR + TAU group: rats were pretreated with ACR (50 mg/kg/day i.p.) for 14 days and then administered TAU (250 mg/kg/day i.g.) for 14 days; TAU group: rats were treated with TAU (250 mg/kg/day i.g.) for 14 days. (c) A gait score was assigned in the range from 1 to 4, where 1—a normal, unaffected gait, 2—a slightly affected gait (tip-toe walking, slight ataxia, and hindlimb weakness), 3—a moderately affected gait (obvious movement abnormalities characterized by dropped hocks and tail dragging), and 4—a severely affected gait (frank hindlimb weakness and inability to rear). ^aP < 0.05, compared with the ACR group.

Figure 2.

Taurine attenuates the damage to axons and the medullary sheath induced by ACR in vivo and in vitro. (a) Electron microscopic analysis was performed in the spinal cord of rats and the representative images were shown. DRG was treated with ACR (0.1 mM) or saline for 24 h and then with taurine (5 mM) in the presence or absence of MK-2206 1 h pretreatment for additional 24 h. Expression of SIM312 (b) and MBP (c) were detected with Western blot. ^aP < 0.05, compared with the control group; ^bP < 0.05, compared with the ACR group; ^cP < 0.05, compared with the TAU + ACR group.

Figure 3.

Effect of taurine on ACR-induced Akt activation in vivo and in vitro. (a) In the in vivo experiment, Akt and p-Akt levels were detected with Western blot. (b) The effects of TAU on the levels of Akt and p-Akt in the spinal cord of ACR-intoxicated rats were detected with Western blot and the density of blots was quantified. DRG was treated with ACR (0.1 mM) or saline for 24 h and then with or without taurine (5 mM). ^aP < 0.05, compared with the control group; ^bP < 0.05, compared with the ACR group.

Figure 4.

Taurine enhanced the p-GSK3β level decreased by ACR in an Akt-dependent manner. (a) The effects of TAU on the levels of p-GSK3β in the spinal cord of ACR-intoxicated rats were detected with Western blot and the density of blots was quantified. (b) DRG was treated with ACR (0.1 mM) or saline for 24 h and then with taurine (5 mM) in the presence or absence of MK-2206 1 h pretreatment for additional 24 h. The p-GSK3β levels were detected with Western blot. GSK3β and p-GSK3β levels were detected with Western blot in (a) (the in vivo experiment) and (b) (the in vitro experiment). In (a), ^aP < 0.05, compared with the control group; ^bP < 0.05, compared with the ACR group; ^cP < 0.05, compared with the ACR + TAU group. In (b), ^aP < 0.05, compared with the control group; ^bP < 0.05, compared with the TAU group; ^cP < 0.05, compared with the TAU + MK-2206 group; ^dP < 0.05, compared with the ACR group; ^eP < 0.05, compared with the ACR + MK-2206 group; ^fP < 0.05, compared with the ACR + TAU group.