TY - JOUR
T1 - High salt induces cognitive impairment via the interaction of the angiotensin II-AT1 and prostaglandin E2-EP1 systems
AU - Kubota, Hisayoshi
AU - Kunisawa, Kazuo
AU - Wulaer, Bolati
AU - Hasegawa, Masaya
AU - Kurahashi, Hitomi
AU - Sakata, Takatoshi
AU - Tezuka, Hiroyuki
AU - Kugita, Masanori
AU - Nagao, Shizuko
AU - Nagai, Taku
AU - Furuyashiki, Tomoyuki
AU - Narumiya, Shuh
AU - Saito, Kuniaki
AU - Nabeshima, Toshitaka
AU - Mouri, Akihiro
N1 - Publisher Copyright:
© 2023 British Pharmacological Society.
PY - 2023/9
Y1 - 2023/9
N2 - 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.
AB - 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.
KW - angiotensin II
KW - cognitive impairment
KW - hypertension
KW - prostaglandin E2
KW - tau hyperphosphorylation
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U2 - 10.1111/bph.16093
DO - 10.1111/bph.16093
M3 - Article
C2 - 37076133
AN - SCOPUS:85159637146
SN - 0007-1188
VL - 180
SP - 2393
EP - 2411
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 18
ER -