The effects of a single intraperitoneal injection of a non-metabolizable glucose analog 2-deoxyglucose (2-DG, 500 mg/kg) on the levels of b-APP expression, and phosphorylated and unphosphorylated tau protein in the rat cerebral cortex were investigated. The effects of 2-DG on the ultrastructure of cortical neurons with particular emphasis on the morphology of the Golgi apparatus, and on brain bioenergetics assessed by in vivo 31P-MRS technique were also evaluated. Seven and a half hours after injection of 2-deoxyglucose a significant increase in brain cortex b-APP expression, increased tau phosphorylation, and a marked relative expansion of the trans- part of the Golgi intracellular secretory pathway in cortical neurons has been found. The changes of b-APP expression and tau phosphorylation appeared within 1 h after 2-DG application and continued for at least 24 h. However, brain 31P resonance spectra remained unchanged for up to 7.5 h after 2-DG. It is suggested that the increase of b-APP expression represents a response of brain tissues to 2-DG-evoked biochemical stress, while tau hyperphosphorylation and the change in Golgi morphology may be secondary phenomena.