High salt induces cognitive impairment via the interaction of the angiotensin II-AT1 and prostaglandin E2-EP1 systems

Hisayoshi Kubota, Kazuo Kunisawa, Bolati Wulaer, Masaya Hasegawa, Hitomi Kurahashi, Takatoshi Sakata, Hiroyuki Tezuka, Masanori Kugita, Shizuko Nagao, Taku Nagai, Tomoyuki Furuyashiki, Shuh Narumiya, Kuniaki Saito, Toshitaka Nabeshima, Akihiro Mouri

研究成果: ジャーナルへの寄稿学術論文査読

3 被引用数 (Scopus)

抄録

Background and Purpose: High salt (HS) intake has been associated with hypertension and cognitive impairment. It is well known that the angiotensin II (Ang II)-AT1 receptor and prostaglandin E2 (PGE2)-EP1 receptor systems are involved in hypertension and neurotoxicity. However, the involvement of these systems in HS-mediated hypertension and emotional and cognitive impairments remains unclear. Experimental Approach: Mice were loaded with HS solution (2% NaCl drinking water) for 12 weeks, and blood pressure was monitored. Subsequently, effects of HS intake on emotional and cognitive function and tau phosphorylation in the prefrontal cortex (PFC) and hippocampus (HIP) were investigated. The involvement of Ang II-AT1 and PGE2-EP1 systems in HS-induced hypertension and neuronal and behavioural impairments was examined by treatment with losartan, an AT1 receptor blocker (ARB), or EP1 gene knockout. Key Results: We demonstrate that hypertension and impaired social behaviour and object recognition memory following HS intake may be associated with tau hyperphosphorylation, decreased phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII), and postsynaptic density protein 95 (PSD95) expression in the PFC and HIP of mice. These changes were blocked by pharmacological treatment with losartan or EP1 receptor gene knockout. Conclusions and Implications: Our findings suggest that the interaction of Ang II-AT1 receptor and PGE2-EP1 receptor systems could be novel therapeutic targets for hypertension-induced cognitive impairment.

本文言語英語
ページ(範囲)2393-2411
ページ数19
ジャーナルBritish Journal of Pharmacology
180
18
DOI
出版ステータス出版済み - 09-2023

All Science Journal Classification (ASJC) codes

  • 薬理学

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