Neurotoxicity of acrylamide in wild type and TNF-α knockout mice

抄録

Background Neurotoxicity of environmental electrophile acrylamide (ACR) has been reported in human and experimental animals. Neuroinflammation is considered as one possible mechanism of ACR neurotoxicity, and increased expression of pro-inflammatory cytokines such as TNF-α has been reported after exposure to ACR. However, the underlying role of TNF-α has not been fully understood. Methods In this study, wild type and TNF-α knockout mice were exposed to ACR at 0, 12.5, or 25mg/kg body weight (bw) by gavage for 4-weeks. Results The result showed that after exposure in both WT and TNF-KO mice the body weight and brain weight significantly decreased. For Functional Observational Battery (FOB) test, the results showed that landing foot spread (LFS) significantly increased in both WT and TNF-KO mice after exposure to ACR, although at 25mg/kg bw exposure, KO mice showed a mild alleviation of LFS increase compared to WT mice. Grip strength of all-limbs and forelimbs significantly decreased after exposure to ACR in both WT and TNF-KO mice. IHC staining showed noradrenergic axon degeneration was alleviated in TNF-KO mice, especially at 12.5mg/kg bw. Real-time PCR showed increased expression of IL-6, SOD-1, CAT, NQO-1, KEAP-1, GCLC, GCLM in both WT and TNF-KO mice; expression of TGF-b, HO-1, MT-1 increased in wild type; expression of GR increased in TNF-KO mice. Conclusion The above results suggest that genetic ablation of pro-inflammatory cytokine TNF-α alleviates neurotoxicity induced by exposure to ACR, especially at 12.5mg/kg exposure. Our findings provide new insight for understanding the role of cytokines in neurodegeneration.