Login Register Cart 0
Generic placeholder image

Current Neurovascular Research

Editor-in-Chief

ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

A Non-Peptidic MAS1 Agonist AVE0991 Alleviates Hippocampal Synaptic Degeneration in Rats with Chronic Cerebral Hypoperfusion

Author(s): Xiao Xue, Rui Duan, Qiao-Quan Zhang, Si-Yu Wang, Peng-Yu Gong, Yan E, Ying-Dong Zhang* and Teng Jiang*

Volume 18, Issue 3, 2021

Published on: 11 October, 2021

Page: [343 - 350] Pages: 8

DOI: 10.2174/1567202618666211012095210

Price: $65

Abstract

Background: Chronic cerebral hypoperfusion (CCH) is a contributing factor for neurodegenerative diseases. As a recently identified heptapeptide of the brain renin-angiotensin system, angiotensin-(1-7) has been revealed to activate its receptor MAS1 and thus ameliorated cognitive impairments in rats with CCH. Since hippocampal synaptic degeneration represents an important pathological basis of cognitive deficits, we hypothesize that activating MAS1-mediated signaling may alleviate CCH-induced synaptic degeneration in the hippocampus.

Methods: In this study, we tested this hypothesis and uncovered the underlying mechanisms in a rat model of CCH induced by bilateral common carotid artery ligation surgery. At one week after the surgery, rats received a daily intraperitoneal vehicle injection or a non-peptidic MAS1 agonist AVE0991 for 8 weeks. During this procedure, Cerebral Blood Flow (CBF) was recorded. The levels of MAS1, amyloid-β (Aβ), neuroinflammatory cytokines, glial cell markers, and synaptophysin in the hippocampus were assessed at the end of the treatment period.

Results: We showed that AVE0991 significantly alleviated hippocampal synaptic degeneration in rats with CCH. This protection might be achieved by facilitating CBF recovery, reducing hippocampal Aβ levels, and suppressing neuroinflammatory responses.

Conclusion: These findings indicate that MAS1-mediated signaling may represent a novel therapeutic target for CCH-related neurodegenerative diseases.

Keywords: Renin-angiotensin System, chronic cerebral hypoperfusion, synaptic degeneration, Ang-(1-7), AVE0991, neuroinflammation.

« Previous Next »
[1]
de la Torre JC. Cerebral hemodynamics and vascular risk factors: setting the stage for Alzheimer’s disease. J Alzheimers Dis 2012; 32(3): 553-67.
[http://dx.doi.org/10.3233/JAD-2012-120793] [PMID: 22842871]
[2]
Duncombe J, Kitamura A, Hase Y, Ihara M, Kalaria RN, Horsburgh K. Chronic cerebral hypoperfusion: A key mechanism leading to vascular cognitive impairment and dementia. Closing the translational gap between rodent models and human vascular cognitive impairment and dementia. Clin Sci (Lond) 2017; 131(19): 2451-68.
[http://dx.doi.org/10.1042/CS20160727] [PMID: 28963120]
[3]
Park JH, Hong JH, Lee SW, et al. The effect of chronic cerebral hypoperfusion on the pathology of Alzheimer’s disease: A positron emission tomography study in rats. Sci Rep 2019; 9(1): 14102.
[http://dx.doi.org/10.1038/s41598-019-50681-4] [PMID: 31575996]
[4]
Shang J, Yamashita T, Zhai Y, et al. Acceleration of NLRP3 inflammasome by chronic cerebral hypoperfusion in Alzheimer’s disease model mouse. Neurosci Res 2019; 143: 61-70.
[http://dx.doi.org/10.1016/j.neures.2018.06.002] [PMID: 29885344]
[5]
Matsuyama H, Shindo A, Shimada T, et al. Chronic cerebral hypoperfusion activates AIM2 and NLRP3 inflammasome. Brain Res 2020; 1736: 146779.
[http://dx.doi.org/10.1016/j.brainres.2020.146779] [PMID: 32171704]
[6]
Ren L, Lu X, Danser AHJ. Revisiting the brain renin-angiotensin system-focus on novel therapies. Curr Hypertens Rep 2019; 21(4): 28.
[http://dx.doi.org/10.1007/s11906-019-0937-8] [PMID: 30949864]
[7]
Kuipers A, Moll GN, Levy A, Krakovsky M, Franklin R. Cyclic angiotensin-(1-7) contributes to rehabilitation of animal performance in a rat model of cerebral stroke. Peptides 2020; 123: 170193.
[http://dx.doi.org/10.1016/j.peptides.2019.170193] [PMID: 31704212]
[8]
Tao MX, Xue X, Gao L, et al. Involvement of angiotensin-(1-7) in the neuroprotection of captopril against focal cerebral ischemia. Neurosci Lett 2018; 687: 16-21.
[http://dx.doi.org/10.1016/j.neulet.2018.09.024] [PMID: 30219484]
[9]
Cao C, Hasegawa Y, Hayashi K, Takemoto Y, Kim-Mitsuyama S. Chronic angiotensin 1-7 infusion prevents angiotensin-II-induced cognitive dysfunction and skeletal muscle injury in a mouse model of Alzheimer’s disease. J Alzheimers Dis 2019; 69(1): 297-309.
[http://dx.doi.org/10.3233/JAD-181000] [PMID: 30958350]
[10]
Kamel AS, Abdelkader NF, Abd El-Rahman SS, Emara M, Zaki HF, Khattab MM. Stimulation of ACE2/ANG(1-7)/mas axis by diminazene ameliorates Alzheimer’s disease in the D-galactose-ovariectomized rat model: Role of PI3K/Akt pathway. Mol Neurobiol 2018; 55(10): 8188-202.
[http://dx.doi.org/10.1007/s12035-018-0966-3] [PMID: 29516284]
[11]
Chen JL, Zhang DL, Sun Y, et al. Angiotensin-(1-7) administration attenuates Alzheimer’s disease-like neuropathology in rats with streptozotocin-induced diabetes via Mas receptor activation. Neuroscience 2017; 346: 267-77.
[http://dx.doi.org/10.1016/j.neuroscience.2017.01.027] [PMID: 28147245]
[12]
Zhou Y, Li M, Zhu DL, et al. Neuroprotective effect of angiotensin-(1-7) against rotenone-induced oxidative damage in CATH. a neurons. Toxicology in vitro: An international journal published in association with BIBRA 2018; 50: 373-82.
[13]
Rabie MA, Abd El Fattah MA, Nassar NN, El-Abhar HS, Abdallah DM. Angiotensin 1-7 ameliorates 6-hydroxydopamine lesions in hemiparkinsonian rats through activation of MAS receptor/PI3K/Akt/BDNF pathway and inhibition of angiotensin II type-1 receptor/NF-κB axis. Biochem Pharmacol 2018; 151: 126-34.
[http://dx.doi.org/10.1016/j.bcp.2018.01.047] [PMID: 29428223]
[14]
Kobiec T, Otero-Losada M, Chevalier G, et al. The renin-angiotensin system modulates dopaminergic neurotransmission: A new player on the scene. Front Synaptic Neurosci 2021; 13: 638519.
[http://dx.doi.org/10.3389/fnsyn.2021.638519] [PMID: 33967734]
[15]
Xie W, Zhu D, Ji L, Tian M, Xu C, Shi J. Angiotensin-(1-7) improves cognitive function in rats with chronic cerebral hypoperfusion. Brain Res 2014; 1573: 44-53.
[http://dx.doi.org/10.1016/j.brainres.2014.05.019] [PMID: 24854124]
[16]
Pini L, Pievani M, Bocchetta M, et al. Brain atrophy in Alzheimer’s Disease and aging. Ageing Res Rev 2016; 30: 25-48.
[http://dx.doi.org/10.1016/j.arr.2016.01.002] [PMID: 26827786]
[17]
Vickers C, Hales P, Kaushik V, et al. Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. J Biol Chem 2002; 277(17): 14838-43.
[http://dx.doi.org/10.1074/jbc.M200581200] [PMID: 11815627]
[18]
Wiemer G, Dobrucki LW, Louka FR, Malinski T, Heitsch H. AVE 0991, a nonpeptide mimic of the effects of angiotensin-(1-7) on the endothelium. Hypertension 2002; 40(6): 847-52.
[http://dx.doi.org/10.1161/01.HYP.0000037979.53963.8F] [PMID: 12468568]
[19]
Wang QG, Xue X, Yang Y, Gong PY, Jiang T, Zhang YD. Angiotensin IV suppresses inflammation in the brains of rats with chronic cerebral hypoperfusion. J Renin Angiotensin Aldosterone Syst 2018; 19(3): 1470320318799587.
[http://dx.doi.org/10.1177/1470320318799587] [PMID: 30223703]
[20]
Santos RA, Ferreira AJ. Pharmacological effects of AVE 0991, a nonpeptide angiotensin-(1-7) receptor agonist. Cardiovasc Drug Rev 2006; 24(3-4): 239-46.
[http://dx.doi.org/10.1111/j.1527-3466.2006.00239.x] [PMID: 17214600]
[21]
Jiang T, Gao L, Shi J, Lu J, Wang Y, Zhang Y. Angiotensin-(1-7) modulates renin-angiotensin system associated with reducing oxidative stress and attenuating neuronal apoptosis in the brain of hypertensive rats. Pharmacol Res 2013; 67(1): 84-93.
[22]
Jiang T, Yu JT, Zhu XC, et al. Angiotensin-(1-7) induces cerebral ischaemic tolerance by promoting brain angiogenesis in a Mas/eNOS-dependent pathway. Br J Pharmacol 2014; 171(18): 4222-32.
[http://dx.doi.org/10.1111/bph.12770] [PMID: 24824997]
[23]
Zhang J, Liu Y, Zheng Y, et al. TREM-2-p38 MAPK signaling regulates neuroinflammation during chronic cerebral hypoperfusion combined with diabetes mellitus. J Neuroinflammation 2020; 17(1): 2.
[http://dx.doi.org/10.1186/s12974-019-1688-9] [PMID: 31900229]
[24]
Duan R, Xue X, Zhang QQ, et al. ACE2 activator diminazene aceturate ameliorates Alzheimer’s disease-like neuropathology and rescues cognitive impairment in SAMP8 mice. Aging (Albany NY) 2020; 12(14): 14819-29.
[http://dx.doi.org/10.18632/aging.103544] [PMID: 32701063]
[25]
Jiang T, Zhang YD, Gao Q, et al. TREM1 facilitates microglial phagocytosis of amyloid beta. Acta Neuropathol 2016; 132(5): 667-83.
[http://dx.doi.org/10.1007/s00401-016-1622-5] [PMID: 27670763]
[26]
Santos RAS, Sampaio WO, Alzamora AC, et al. The ACE2/Angiotensin-(1-7)/MAS Axis of the Renin-Angiotensin System: Focus on Angiotensin-(1-7). Physiol Rev 2018; 98(1): 505-53.
[http://dx.doi.org/10.1152/physrev.00023.2016] [PMID: 29351514]
[27]
Derdeyn CP, Videen TO, Fritsch SM, Carpenter DA, Grubb RL Jr, Powers WJ. Compensatory mechanisms for chronic cerebral hypoperfusion in patients with carotid occlusion. Stroke 1999; 30(5): 1019-24.
[http://dx.doi.org/10.1161/01.STR.30.5.1019] [PMID: 10229738]
[28]
Busch HJ, Schirmer SH, Jost M, et al. Leptin augments cerebral hemodynamic reserve after three-vessel occlusion: distinct effects on cerebrovascular tone and proliferation in a nonlethal model of hypoperfused rat brain. J Cereb Blood Flow Metab 2011; 31(4): 1085-92.
[http://dx.doi.org/10.1038/jcbfm.2010.192] [PMID: 20978518]
[29]
Raffai G, Lombard JH. Angiotensin-(1-7) selectively induces relaxation and modulates endothelium-dependent dilation in mesenteric arteries of salt-fed rats. J Vasc Res 2016; 53(1-2): 105-18.
[http://dx.doi.org/10.1159/000448714] [PMID: 27676088]
[30]
Yousif MHM, Benter IF, Diz DI, Chappell MC. Angiotensin-(1-7)-dependent vasorelaxation of the renal artery exhibits unique angiotensin and bradykinin receptor selectivity. Peptides 2017; 90: 10-6.
[http://dx.doi.org/10.1016/j.peptides.2017.02.001] [PMID: 28192151]
[31]
Zhang F, Xu Y, Pan Y, et al. Effects of angiotensin-(1-7) and angiotensin II on acetylcholine-induced vascular relaxation in spontaneously hypertensive rats. Oxid Med Cell Longev 2019; 2019: 6512485.
[http://dx.doi.org/10.1155/2019/6512485] [PMID: 31827689]
[32]
Wang L, Du Y, Wang K, Xu G, Luo S, He G. Chronic cerebral hypoperfusion induces memory deficits and facilitates Abeta generation in C57BL/6J mice. Experimental neurology 2016; 283(Pt A): 353-64.
[33]
Cai Z, Liu Z, Xiao M, Wang C, Tian F. Chronic cerebral hypoperfusion promotes amyloid-beta pathogenesis via activating β/γ-secretases. Neurochem Res 2017; 42(12): 3446-55.
[http://dx.doi.org/10.1007/s11064-017-2391-9] [PMID: 28836062]
[34]
Wilkins HM, Swerdlow RH. Amyloid precursor protein processing and bioenergetics. Brain Res Bull 2017; 133: 71-9.
[http://dx.doi.org/10.1016/j.brainresbull.2016.08.009] [PMID: 27545490]
[35]
Yang H, Wang W, Jia L, et al. The effect of chronic cerebral hypoperfusion on blood-brain barrier permeability in a transgenic Alzheimer’s disease mouse model (PS1V97L). J Alzheimers Dis 2020; 74(1): 261-75.
[http://dx.doi.org/10.3233/JAD-191045] [PMID: 32007956]
[36]
Ashok A, Rai NK, Raza W, Pandey R, Bandyopadhyay S. Chronic cerebral hypoperfusion-induced impairment of Aβ clearance requires HB-EGF-dependent sequential activation of HIF1α and MMP9. Neurobiol Dis 2016; 95: 179-93.
[http://dx.doi.org/10.1016/j.nbd.2016.07.013] [PMID: 27431094]
[37]
Yin C, Deng Y, Liu Y, Gao J, Yan L, Gong Q. Icariside II ameliorates cognitive impairments induced by chronic cerebral hypoperfusion by inhibiting the amyloidogenic pathway: Involvement of BDNF/TrkB/CREB signaling and up-regulation of PPARα and PPARγ in rats. Front Pharmacol 2018; 9: 1211.
[http://dx.doi.org/10.3389/fphar.2018.01211] [PMID: 30405422]
[38]
Wang J, Zhang HY, Tang XC. Huperzine a improves chronic inflammation and cognitive decline in rats with cerebral hypoperfusion. J Neurosci Res 2010; 88(4): 807-15.
[PMID: 19795377]
[39]
Ransohoff RM. How neuroinflammation contributes to neurodegeneration. Science 2016; 353(6301): 777-83.
[http://dx.doi.org/10.1126/science.aag2590] [PMID: 27540165]
[40]
Townsend KP, Obregon D, Quadros A, et al. Proinflammatory and vasoactive effects of Abeta in the cerebrovasculature. Ann N Y Acad Sci 2002; 977: 65-76.
[http://dx.doi.org/10.1111/j.1749-6632.2002.tb04799.x] [PMID: 12480734]
[41]
Zhai Y, Yamashita T, Nakano Y, et al. Chronic cerebral hypoperfusion accelerates Alzheimer’s disease pathology with cerebrovascular remodeling in a novel mouse model. J Alzheimers Dis 2016; 53(3): 893-905.
[http://dx.doi.org/10.3233/JAD-160345] [PMID: 27314529]
[42]
Liu M, Shi P, Sumners C. Direct anti-inflammatory effects of angiotensin-(1-7) on microglia. J Neurochem 2016; 136(1): 163-71.
[http://dx.doi.org/10.1111/jnc.13386] [PMID: 26448556]
[43]
Jiang T, Xue LJ, Yang Y, et al. AVE0991, a nonpeptide analogue of Ang-(1-7), attenuates aging-related neuroinflammation. Aging (Albany NY) 2018; 10(4): 645-57.
[http://dx.doi.org/10.18632/aging.101419] [PMID: 29667931]
[44]
Moore ED, Kooshki M, Metheny-Barlow LJ, Gallagher PE, Robbins ME. Angiotensin-(1-7) prevents radiation-induced inflammation in rat primary astrocytes through regulation of MAP kinase signaling. Free Radic Biol Med 2013; 65: 1060-8.
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.08.183] [PMID: 24012919]
[45]
Chang RL, Lin JW, Kuo WW, et al. Angiotensin-(1-7) attenuated long-term hypoxia-stimulated cardiomyocyte apoptosis by inhibiting HIF-1α nuclear translocation via Mas receptor regulation. Growth Factors 2016; 34(1-2): 11-8.
[http://dx.doi.org/10.3109/08977194.2016.1155150] [PMID: 27055565]
[46]
Jarajapu YP, Bhatwadekar AD, Caballero S, et al. Activation of the ACE2/angiotensin-(1-7)/Mas receptor axis enhances the reparative function of dysfunctional diabetic endothelial progenitors. Diabetes 2013; 62(4): 1258-69.
[http://dx.doi.org/10.2337/db12-0808] [PMID: 23230080]

Rights & Permissions Print Cite
Article Metrics
43
1
© 2024 Bentham Science Publishers | Privacy Policy