Direct stimulation of angiotensin II type 2 receptor enhances spatial memory

Fei Jing, Masaki Mogi, Akiko Sakata, Jun Iwanami, Kana Tsukuda, Kousei Ohshima, Li-Juan Min, Ulrike Muscha Steckelings, Thomas Unger, Björn Dahlöf, Masatsugu Horiuchi

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

We examined the possibility that direct stimulation of the angiotensin II type 2 (AT(2)) receptor by a newly generated direct AT(2) receptor agonist, Compound 21 (C21), enhances cognitive function. Treatment with C21 intraperitoneal injection for 2 weeks significantly enhanced cognitive function evaluated by the Morris water maze test in C57BL6 mice, but this effect was not observed in AT(2) receptor-deficient mice. However, C21-induced cognitive enhancement in C57BL6 mice was attenuated by coadministration of icatibant, a bradykinin B(2) receptor antagonist. Administration of C21 dose dependently increased cerebral blood flow assessed by laser speckle flowmetry and hippocampal field-excitatory postsynaptic potential (f-EPSP) determined by electrophysiological techniques in C57BL6 mice. Furthermore, activation of the AT(2) receptor by C21 promoted neurite outgrowth of cultured hippocampal neurons prepared from fetal transgenic mice expressing green fluorescent protein. Finally, we investigated the pathologic relevance of C21 for spatial learning using an Alzheimer's disease mouse model with intracerebroventricular injection of amyloid-β (1 to 40). We observed that treatment with C21 prevented cognitive decline in this model. These results suggest that a direct AT(2) receptor agonist, C21, enhances cognitive function at least owing to an increase in CBF, enhancement of f-EPSP, and neurite outgrowth in hippocampal neurons.
OriginalsprogEngelsk
TidsskriftJournal of Cerebral Blood Flow and Metabolism
Vol/bind32
Udgave nummer2
Sider (fra-til)248-255
ISSN0271-678X
DOI
StatusUdgivet - 2012

Fingeraftryk

Angiotensin Type 2 Receptor
Cognition
Excitatory Postsynaptic Potentials
Neurons
Rheology
Green Fluorescent Proteins
Intraperitoneal Injections
Alzheimer Disease
Spatial Memory

Citer dette

Jing, F., Mogi, M., Sakata, A., Iwanami, J., Tsukuda, K., Ohshima, K., ... Horiuchi, M. (2012). Direct stimulation of angiotensin II type 2 receptor enhances spatial memory. Journal of Cerebral Blood Flow and Metabolism, 32(2), 248-255. https://doi.org/10.1038/jcbfm.2011.133
Jing, Fei ; Mogi, Masaki ; Sakata, Akiko ; Iwanami, Jun ; Tsukuda, Kana ; Ohshima, Kousei ; Min, Li-Juan ; Steckelings, Ulrike Muscha ; Unger, Thomas ; Dahlöf, Björn ; Horiuchi, Masatsugu. / Direct stimulation of angiotensin II type 2 receptor enhances spatial memory. I: Journal of Cerebral Blood Flow and Metabolism. 2012 ; Bind 32, Nr. 2. s. 248-255.
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title = "Direct stimulation of angiotensin II type 2 receptor enhances spatial memory",
abstract = "We examined the possibility that direct stimulation of the angiotensin II type 2 (AT(2)) receptor by a newly generated direct AT(2) receptor agonist, Compound 21 (C21), enhances cognitive function. Treatment with C21 intraperitoneal injection for 2 weeks significantly enhanced cognitive function evaluated by the Morris water maze test in C57BL6 mice, but this effect was not observed in AT(2) receptor-deficient mice. However, C21-induced cognitive enhancement in C57BL6 mice was attenuated by coadministration of icatibant, a bradykinin B(2) receptor antagonist. Administration of C21 dose dependently increased cerebral blood flow assessed by laser speckle flowmetry and hippocampal field-excitatory postsynaptic potential (f-EPSP) determined by electrophysiological techniques in C57BL6 mice. Furthermore, activation of the AT(2) receptor by C21 promoted neurite outgrowth of cultured hippocampal neurons prepared from fetal transgenic mice expressing green fluorescent protein. Finally, we investigated the pathologic relevance of C21 for spatial learning using an Alzheimer's disease mouse model with intracerebroventricular injection of amyloid-β (1 to 40). We observed that treatment with C21 prevented cognitive decline in this model. These results suggest that a direct AT(2) receptor agonist, C21, enhances cognitive function at least owing to an increase in CBF, enhancement of f-EPSP, and neurite outgrowth in hippocampal neurons.",
author = "Fei Jing and Masaki Mogi and Akiko Sakata and Jun Iwanami and Kana Tsukuda and Kousei Ohshima and Li-Juan Min and Steckelings, {Ulrike Muscha} and Thomas Unger and Bj{\"o}rn Dahl{\"o}f and Masatsugu Horiuchi",
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Jing, F, Mogi, M, Sakata, A, Iwanami, J, Tsukuda, K, Ohshima, K, Min, L-J, Steckelings, UM, Unger, T, Dahlöf, B & Horiuchi, M 2012, 'Direct stimulation of angiotensin II type 2 receptor enhances spatial memory', Journal of Cerebral Blood Flow and Metabolism, bind 32, nr. 2, s. 248-255. https://doi.org/10.1038/jcbfm.2011.133

Direct stimulation of angiotensin II type 2 receptor enhances spatial memory. / Jing, Fei; Mogi, Masaki; Sakata, Akiko; Iwanami, Jun; Tsukuda, Kana; Ohshima, Kousei; Min, Li-Juan; Steckelings, Ulrike Muscha; Unger, Thomas; Dahlöf, Björn; Horiuchi, Masatsugu.

I: Journal of Cerebral Blood Flow and Metabolism, Bind 32, Nr. 2, 2012, s. 248-255.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Direct stimulation of angiotensin II type 2 receptor enhances spatial memory

AU - Jing, Fei

AU - Mogi, Masaki

AU - Sakata, Akiko

AU - Iwanami, Jun

AU - Tsukuda, Kana

AU - Ohshima, Kousei

AU - Min, Li-Juan

AU - Steckelings, Ulrike Muscha

AU - Unger, Thomas

AU - Dahlöf, Björn

AU - Horiuchi, Masatsugu

PY - 2012

Y1 - 2012

N2 - We examined the possibility that direct stimulation of the angiotensin II type 2 (AT(2)) receptor by a newly generated direct AT(2) receptor agonist, Compound 21 (C21), enhances cognitive function. Treatment with C21 intraperitoneal injection for 2 weeks significantly enhanced cognitive function evaluated by the Morris water maze test in C57BL6 mice, but this effect was not observed in AT(2) receptor-deficient mice. However, C21-induced cognitive enhancement in C57BL6 mice was attenuated by coadministration of icatibant, a bradykinin B(2) receptor antagonist. Administration of C21 dose dependently increased cerebral blood flow assessed by laser speckle flowmetry and hippocampal field-excitatory postsynaptic potential (f-EPSP) determined by electrophysiological techniques in C57BL6 mice. Furthermore, activation of the AT(2) receptor by C21 promoted neurite outgrowth of cultured hippocampal neurons prepared from fetal transgenic mice expressing green fluorescent protein. Finally, we investigated the pathologic relevance of C21 for spatial learning using an Alzheimer's disease mouse model with intracerebroventricular injection of amyloid-β (1 to 40). We observed that treatment with C21 prevented cognitive decline in this model. These results suggest that a direct AT(2) receptor agonist, C21, enhances cognitive function at least owing to an increase in CBF, enhancement of f-EPSP, and neurite outgrowth in hippocampal neurons.

AB - We examined the possibility that direct stimulation of the angiotensin II type 2 (AT(2)) receptor by a newly generated direct AT(2) receptor agonist, Compound 21 (C21), enhances cognitive function. Treatment with C21 intraperitoneal injection for 2 weeks significantly enhanced cognitive function evaluated by the Morris water maze test in C57BL6 mice, but this effect was not observed in AT(2) receptor-deficient mice. However, C21-induced cognitive enhancement in C57BL6 mice was attenuated by coadministration of icatibant, a bradykinin B(2) receptor antagonist. Administration of C21 dose dependently increased cerebral blood flow assessed by laser speckle flowmetry and hippocampal field-excitatory postsynaptic potential (f-EPSP) determined by electrophysiological techniques in C57BL6 mice. Furthermore, activation of the AT(2) receptor by C21 promoted neurite outgrowth of cultured hippocampal neurons prepared from fetal transgenic mice expressing green fluorescent protein. Finally, we investigated the pathologic relevance of C21 for spatial learning using an Alzheimer's disease mouse model with intracerebroventricular injection of amyloid-β (1 to 40). We observed that treatment with C21 prevented cognitive decline in this model. These results suggest that a direct AT(2) receptor agonist, C21, enhances cognitive function at least owing to an increase in CBF, enhancement of f-EPSP, and neurite outgrowth in hippocampal neurons.

U2 - 10.1038/jcbfm.2011.133

DO - 10.1038/jcbfm.2011.133

M3 - Journal article

VL - 32

SP - 248

EP - 255

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 2

ER -