釘田 雅則

High salt (HS) intake is known as a risk factor for hypertension and dementia. Prostaglandin E2 (PGE2) has various effects on vascular function and central nervous system via four types of PGE2 receptors (EP1-EP4). However, an involvement of PGE2/EP1 signaling in the HS intake-induced hypertension and emotional and cognitive dysfunctions is still unclear. In this study, we confirmed the effect of HS intake on the blood pressure and emotional and cognitive functions in mice. Mice showed hypertension and impairments of social behavior in social interaction test and object recognition memory in novel object recognition test 12 weeks after HS intake. HS intake increased phosphorylation of tau, but decreased phosphorylation of Ca2+ / calmodulin-dependent protein kinase II and expression of PSD95 in the prefrontal cortex. HS intake increased expressions of mRNA of EP1 receptor in the kidney and prefrontal cortex. The HS intake-induced hypertension, abnormal behaviors and increased phosphorylation of tau were not observed in the EP1 heterozygous knockout mice. These findings suggest that PGE2/EP1-tau phosphorylation signaling is involved in the HS intake-induced hypertension and emotional and cognitive dysfunctions.

High salt (HS) intake is known as a risk factor for hypertension and dementia. However, an involvement of the brain-peripheral interaction in the HS-induced hypertension and cognitive dysfunction is still unclear. In this study, we confirmed the effect of HS intake on the blood pressure and cognitive and emotional functions in mice. Mice showed hypertension and impairments of object recognition memory in novel object recognition test and social behavior in social interaction test 12 weeks after HS intake. We investigated the mechanism of HS intake-induced hypertension and abnormal behaviors. HS intake increased phosphorylation of tau and decreased phosphorylation of Ca2+ / calmodulin-dependent protein kinase II (CaMKII) and expression of PSD95 in the prefrontal cortex and hippocampus, suggesting HS intake induces neuronal dysfunction. On the other hand, HS intake increased mRNA levels of inducible nitric oxide synthase (iNOS) and serum amyloid A (SAA) in the small intestine and picolinic acid levels in the serum, suggesting HS intake induces peripheral inflammatory response. The present findings suggest that HS intake induces hypertension and abnormal behaviors with peripheral inflammatory response.