High salt induces cognitive impairment via the angiotensin II-AT1 and prostaglandin E2-EP1 systems
High salt induces cognitive impairment via the angiotensin II-AT1 and prostaglandin E2-EP1 systems
Abstract High salt (HS) intake is a known risk factor for hypertension and dementia. Clinical studies have shown that antihypertensive drugs can decrease the incidence of dementia. Accordingly, a strong relationship can be suggested between hypertension and cognitive impairment. It is well-known that angiotensin II (Ang II)-AT1 and prostaglandin E2 (PGE2)-EP1 systems are involved in hypertension and neurotoxicity. However, the involvement of these systems in HS-mediated hypertension and emotional and cognitive impairments remains unclear. Herein, we demonstrated that hypertension and impaired social behavior and object recognition memory following HS intake could be associated with tau hyperphosphorylation, decreased phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII), and postsynaptic density protein 95 (PSD95) expression in the prefrontal cortex and hippocampus of mice. These changes were blocked by pharmacological treatment with losartan, an Ang II receptor blocker (ARB), or EP1 gene knockout. Our findings suggest that Ang II-AT1 and PGE2-EP1 systems could be novel therapeutic targets for hypertension-induced dementia.
Nagai Taku、Kurahashi Hitomi、Saito Kuniaki、Mouri Akihiro、Kunisawa Kazuo、Hasegawa Masaya、Tezuka Hiroyuki、Nagao Shizuko、Furuyashiki Tomoyuki、Narumiya Shuh、Kugita Masanori、Sakata Takatoshi、Kubota Hisayoshi、Wulaer Bolati、Nabeshima Toshitaka
Division of Behavioral Neuropharmacology International Center for Brain Science (ICBS), Fujita Health UniversityDepartment of Regulatory Science for Evaluation & Development of Pharmaceuticals & Devices, Fujita Health University Graduate School of Health ScienceDepartment of Disease Control and Prevention, Fujita Health University Graduate School of Health Science||Laboratory of Health and Medical Science Innovation (HMSI) and International Center for Brain Science (ICBS), Fujita Health University Graduate School of Health Science||Japanese Drug Organization of Appropriate Use and ResearchDepartment of Regulatory Science for Evaluation & Development of Pharmaceuticals & Devices, Fujita Health University Graduate School of Health Science||Japanese Drug Organization of Appropriate Use and ResearchDepartment of Regulatory Science for Evaluation & Development of Pharmaceuticals & Devices, Fujita Health University Graduate School of Health ScienceDepartment of Regulatory Science for Evaluation & Development of Pharmaceuticals & Devices, Fujita Health University Graduate School of Health ScienceDepartment of Cellular Function Analysis, Research Promotion and Support Headquarters, Fujita Health UniversityEducation and Research Facility of Animal Models for Human Diseases, Center for Research Promotion and Support, Fujita Health UniversityDivision of Pharmacology, Graduate School of Medicine, Kobe UniversityDepartment of Drug Discovery Medicine, Kyoto University Graduate School of MedicineEducation and Research Facility of Animal Models for Human Diseases, Center for Research Promotion and Support, Fujita Health UniversityDepartment of Regulatory Science for Evaluation & Development of Pharmaceuticals & Devices, Fujita Health University Graduate School of Health ScienceDepartment of Regulatory Science for Evaluation & Development of Pharmaceuticals & Devices, Fujita Health University Graduate School of Health ScienceLaboratory of Health and Medical Science Innovation (HMSI) and International Center for Brain Science (ICBS), Fujita Health University Graduate School of Health ScienceLaboratory of Health and Medical Science Innovation (HMSI) and International Center for Brain Science (ICBS), Fujita Health University Graduate School of Health Science||Japanese Drug Organization of Appropriate Use and Research
神经病学、精神病学基础医学内科学
angiotensin IIdementiahypertensionprostaglandin E2tau hyperphosphorylation
Nagai Taku,Kurahashi Hitomi,Saito Kuniaki,Mouri Akihiro,Kunisawa Kazuo,Hasegawa Masaya,Tezuka Hiroyuki,Nagao Shizuko,Furuyashiki Tomoyuki,Narumiya Shuh,Kugita Masanori,Sakata Takatoshi,Kubota Hisayoshi,Wulaer Bolati,Nabeshima Toshitaka.High salt induces cognitive impairment via the angiotensin II-AT1 and prostaglandin E2-EP1 systems[EB/OL].(2025-03-28)[2025-04-28].https://www.biorxiv.org/content/10.1101/2022.06.06.495007.点此复制
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