Blood RNA-sequencing analysis in acrylamide-induced neurotoxicity and depressive symptoms in rats

Acrylamide (ACR) is a by-product of the Maillard reaction, which occurs when food reacts at high temperatures. Occupational exposure is a risk factor for chronic ACR toxicity. ACR may cause neurotoxicity and depressive symptoms with high concentration in the blood; however, the underlying mechanism remains unknown. We showed the rats developed neurotoxic symptoms after being fed with ACR for 28 days, such as reduced activity and hind limb muscle weakness. We investigated whether ACR exposure causes gene expression differences by blood RNA sequencing and analyzed the differential expression of depressive symptoms-associated genes. The result indicated that IFN-γ the key regulator of neurotoxicity and depressive symptoms was induced by ACR. ACR induced the ubiquitin-mediated proteolysis pathway and JAK/STAT pathways gene expression. ACR upregulated the expression of IFN-γ, inducing neuroinflammation and neurotoxicity. ACR also upregulated the expression of JAK2, STAT1, PI3K, AKT, IκBα, UBE2D4, NF-κB, TNF-α, and iNOS in rat brain tissues and Neuro-2a cells. Thus, IFN-γ induction by ACR may induce depressive symptoms, and the ubiquitin-mediated proteolysis pathway and JAK/STAT pathways may involve in ACR neurotoxicity and depressive symptoms.