Thiamine (vitamin B1) deficiency (TD) causes mild and chronic impairment of oxidative metabolism and induces neuronal death in specific brain regions.The mechanisms underlying TD-induced cell death,however,remain unclear.The double-stranded RNA (dsRNA)-activated protein kinase (PKR) has been well known for its anti-viral function.Upon activation by viral infection or dsRNA,PKR phosphorylates its substrate,the α-subunit of eukaryotic translation factor-2 (eIF2α),leading to inhibition of translation.In response to various cellular stresses,PKR can also be stimulated by its protein activators,PACT,or its mouse homologue RAX.We demonstrated that TD in mice induced phosphorylation of PKR at Thr446 and Thr451 and phosphorylation of eIF2α at Ser51 in the cerebellum and the thalamus.