Although increasing evidences suggest a relationship between hypertension and brain function for years, it is still unclear whether hypertension constitutes a risk factor for cognitive decline and its underlying mechanism. In the present study, an experimental animal model of hypertension simply by feeding rats with high salt diet was employed. We found that long-term high salt intake caused a marked increase of systolic blood pressure linked to a declined regional cerebral blood flow. Fear conditioning and morris water maze behavioral test revealed that high salt diet induced hippocampal dependent spatial reference memory deficits, while a decreased synaptogenesis without neuronal loss in hippocampus was observed in high salt treated rats. Furthermore, we found that high salt induced a decrease of intracellular calcium, which inactivated CaMK II and resulted in dephosphorylation of CREB at Ser133. These findings suggest a novel etiopathogenic mechanism of cognitive deficit induced by hypertension, which is initiated by high salt diet.
Keywords: cerebral blood flow; cognitive defects; high salt diet; hypertension; synaptogenesis.