High salt induces cognitive impairment via the interaction of the angiotensin II-AT 1 and prostaglandin E2-EP 1 systems.

Autor: Kubota H; Department of Regulatory Science for Evaluation & Development of Pharmaceuticals & Devices, Fujita Health University Graduate School of Health Science, Toyoake, Aichi, Japan., Kunisawa K; Department of Regulatory Science for Evaluation & Development of Pharmaceuticals & Devices, Fujita Health University Graduate School of Health Science, Toyoake, Aichi, Japan., Wulaer B; Laboratory of Health and Medical Science Innovation (HMSI), Fujita Health University Graduate School of Health Science, Toyoake, Aichi, Japan., Hasegawa M; Department of Regulatory Science for Evaluation & Development of Pharmaceuticals & Devices, Fujita Health University Graduate School of Health Science, Toyoake, Aichi, Japan., Kurahashi H; Department of Regulatory Science for Evaluation & Development of Pharmaceuticals & Devices, Fujita Health University Graduate School of Health Science, Toyoake, Aichi, Japan., Sakata T; Department of Regulatory Science for Evaluation & Development of Pharmaceuticals & Devices, Fujita Health University Graduate School of Health Science, Toyoake, Aichi, Japan., Tezuka H; Department of Cellular Function Analysis, Research Promotion and Support Headquarters, Fujita Health University, Toyoake, Aichi, Japan., Kugita M; Education and Research Facility of Animal Models for Human Diseases, Center for Research Promotion and Support, Fujita Health University, Toyoake, Aichi, Japan., Nagao S; Education and Research Facility of Animal Models for Human Diseases, Center for Research Promotion and Support, Fujita Health University, Toyoake, Aichi, Japan., Nagai T; Division of Behavioral Neuropharmacology International Center for Brain Science (ICBS), Fujita Health University, Toyoake, Aichi, Japan., Furuyashiki T; Division of Pharmacology, Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan., Narumiya S; Department of Drug Discovery Medicine, Kyoto University Graduate School of Medicine, Kyoto, Kyoto, Japan., Saito K; Laboratory of Health and Medical Science Innovation (HMSI), Fujita Health University Graduate School of Health Science, Toyoake, Aichi, Japan.; Department of Disease Control and Prevention, Fujita Health University Graduate School of Health Science, Toyoake, Aichi, Japan.; Japanese Drug Organization of Appropriate Use and Research, Nagoya, Aichi, Japan., Nabeshima T; Laboratory of Health and Medical Science Innovation (HMSI), Fujita Health University Graduate School of Health Science, Toyoake, Aichi, Japan.; Japanese Drug Organization of Appropriate Use and Research, Nagoya, Aichi, Japan., Mouri A; Department of Regulatory Science for Evaluation & Development of Pharmaceuticals & Devices, Fujita Health University Graduate School of Health Science, Toyoake, Aichi, Japan.; Japanese Drug Organization of Appropriate Use and Research, Nagoya, Aichi, Japan.
Jazyk: angličtina
Zdroj: British journal of pharmacology [Br J Pharmacol] 2023 Sep; Vol. 180 (18), pp. 2393-2411. Date of Electronic Publication: 2023 May 17.
DOI: 10.1111/bph.16093
Abstrakt: 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)-AT 1 receptor and prostaglandin E2 (PGE2)-EP 1 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-AT 1 and PGE2-EP 1 systems in HS-induced hypertension and neuronal and behavioural impairments was examined by treatment with losartan, an AT 1 receptor blocker (ARB), or EP 1 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 Ca 2+ /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 EP 1 receptor gene knockout.
Conclusions and Implications: Our findings suggest that the interaction of Ang II-AT 1 receptor and PGE2-EP 1 receptor systems could be novel therapeutic targets for hypertension-induced cognitive impairment.
(© 2023 British Pharmacological Society.)
Databáze: MEDLINE
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