AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway

The renin-angiotensin system (RAS) is a paracrine RAS within the central nervous system (CNS) and is closely related to Alzheimer’s disease (AD). The endogenous hexapeptide angiotensin IV (Ang IV), an important component of the brain RAS, was found to rescue cognitive impairment and recover memory i...

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Autores principales:	Xiaojin Sun, Yang Deng, Xinxin Fu, Siyu Wang, Rui Duan, Yingdong Zhang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Alzheimer’s disease Dihexa cognitive PI3K/AKT Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/fa0b1a5489b741a98e156e1bda147186
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spelling	oai:doaj.org-article:fa0b1a5489b741a98e156e1bda1471862021-11-25T16:58:20ZAngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway10.3390/brainsci111114872076-3425https://doaj.org/article/fa0b1a5489b741a98e156e1bda1471862021-11-01T00:00:00Zhttps://www.mdpi.com/2076-3425/11/11/1487https://doaj.org/toc/2076-3425The renin-angiotensin system (RAS) is a paracrine RAS within the central nervous system (CNS) and is closely related to Alzheimer’s disease (AD). The endogenous hexapeptide angiotensin IV (Ang IV), an important component of the brain RAS, was found to rescue cognitive impairment and recover memory in previous studies. In our study, we used different doses of Dihexa, which can be orally administered and cross the BBB in APP/PS1 mice. We found that the amount of AngIV in mouse tissue increased after the administration of Dihexa compared to that in the WT group. Meanwhile, Dihexa restored spatial learning and cognitive functions in the Morris water maze test. Dihexa increased the neuronal cells and the expression of SYP protein in APP/PS1 mice in Nissl staining. Furthermore, Dihexa decreased the activation of astrocytes and microglia, markedly reduced levels of the pro-inflammatory cytokines IL-1β and TNF-α and increased the levels of the anti-inflammatory cytokine IL-10. Dihexa activated the PI3K/AKT signaling pathway, while PI3K inhibitor wortmannin significantly reversed the anti-inflammatory and anti-apoptotic effects of APP/PS1 mice. These findings highlight the brain AngIV/PI3K/AKT axis as a potential target for the treatment of AD.Xiaojin SunYang DengXinxin FuSiyu WangRui DuanYingdong ZhangMDPI AGarticleAlzheimer’s diseaseDihexacognitivePI3K/AKTNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENBrain Sciences, Vol 11, Iss 1487, p 1487 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Alzheimer’s disease Dihexa cognitive PI3K/AKT Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Alzheimer’s disease Dihexa cognitive PI3K/AKT Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Xiaojin Sun Yang Deng Xinxin Fu Siyu Wang Rui Duan Yingdong Zhang AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway
description	The renin-angiotensin system (RAS) is a paracrine RAS within the central nervous system (CNS) and is closely related to Alzheimer’s disease (AD). The endogenous hexapeptide angiotensin IV (Ang IV), an important component of the brain RAS, was found to rescue cognitive impairment and recover memory in previous studies. In our study, we used different doses of Dihexa, which can be orally administered and cross the BBB in APP/PS1 mice. We found that the amount of AngIV in mouse tissue increased after the administration of Dihexa compared to that in the WT group. Meanwhile, Dihexa restored spatial learning and cognitive functions in the Morris water maze test. Dihexa increased the neuronal cells and the expression of SYP protein in APP/PS1 mice in Nissl staining. Furthermore, Dihexa decreased the activation of astrocytes and microglia, markedly reduced levels of the pro-inflammatory cytokines IL-1β and TNF-α and increased the levels of the anti-inflammatory cytokine IL-10. Dihexa activated the PI3K/AKT signaling pathway, while PI3K inhibitor wortmannin significantly reversed the anti-inflammatory and anti-apoptotic effects of APP/PS1 mice. These findings highlight the brain AngIV/PI3K/AKT axis as a potential target for the treatment of AD.
format	article
author	Xiaojin Sun Yang Deng Xinxin Fu Siyu Wang Rui Duan Yingdong Zhang
author_facet	Xiaojin Sun Yang Deng Xinxin Fu Siyu Wang Rui Duan Yingdong Zhang
author_sort	Xiaojin Sun
title	AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway
title_short	AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway
title_full	AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway
title_fullStr	AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway
title_full_unstemmed	AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway
title_sort	angiv-analog dihexa rescues cognitive impairment and recovers memory in the app/ps1 mouse via the pi3k/akt signaling pathway
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/fa0b1a5489b741a98e156e1bda147186
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AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway

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