Inhibition of NOD1 Attenuates Neonatal Hypoxia-Ischemia Induced Long-Term Cognitive Impairments in Mice Through Modulation of Autophagy-Related Proteins

Fang Liu,1 Mingyu Shao,1 Feng Xu,2 Fang Rong3 1Department of Child Health Care, Zibo Central Hospital, Zibo, 255000, Shandong, People’s Republic of China; 2Department of Pediatrics, Zibo Central Hospital, Zibo, 255000, Shandong, People’s Republic of China; 3The Community Clinic of Overseas Chinese T...

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Autores principales:	Liu F, Shao M, Xu F, Rong F
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	neonatal hypoxia-ischemia cognitive impairment nod1 autophagy Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/e446a5cdbf9f4b35acc2846e02aefae9
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spelling	oai:doaj.org-article:e446a5cdbf9f4b35acc2846e02aefae92021-12-02T16:28:08ZInhibition of NOD1 Attenuates Neonatal Hypoxia-Ischemia Induced Long-Term Cognitive Impairments in Mice Through Modulation of Autophagy-Related Proteins1178-2021https://doaj.org/article/e446a5cdbf9f4b35acc2846e02aefae92021-08-01T00:00:00Zhttps://www.dovepress.com/inhibition-of-nod1-attenuates-neonatal-hypoxia-ischemia-induced-long-t-peer-reviewed-fulltext-article-NDThttps://doaj.org/toc/1178-2021Fang Liu,1 Mingyu Shao,1 Feng Xu,2 Fang Rong3 1Department of Child Health Care, Zibo Central Hospital, Zibo, 255000, Shandong, People’s Republic of China; 2Department of Pediatrics, Zibo Central Hospital, Zibo, 255000, Shandong, People’s Republic of China; 3The Community Clinic of Overseas Chinese Town, Zibo Central Hospital, North Gate of Zhongrun Overseas Chinese Town, Zibo, 255000, Shandong, People’s Republic of ChinaCorrespondence: Fang RongThe Community Clinic of Overseas Chinese Town, Zibo Central Hospital, North Gate of Zhongrun Overseas Chinese Town, Zhangdian District, Zibo, 255000, Shandong, People’s Republic of ChinaTel +86-18678186178Email rongfang0817@163.comBackground: Autophagy is implicated in neonatal hypoxia-ischemia (HI) induced cognitive impairment. The nucleotide-oligomerizing domain-1 (NOD1), a protein involved in inflammatory responses, has been shown to activate autophagy to promote progression of other diseases. We aimed to investigate whether and how NOD1 is involved in HI-induced brain injury using an HI mouse model.Methods: We induced HI in neonatal mice and examined levels of NOD1 and genes associated with autophagy. We then inhibited NOD1 by intracerebroventricular injection of si-NOD1 following HI induction and tested the effects on autophagy, inflammatory responses and long-term behavioral outcomes through Morris water maze and open field tests.Results: We found that HI induction significantly elevated mRNA levels of NOD1 (3.54 folds change) and autophagy-related genes including Atg5 (3.89 folds change) and Beclin-1 (3.34 folds change). NOD1 inhibition following HI induction suppressed autophagy signaling as well as HI induced proinflammatory cytokine production. Importantly, NOD1 inhibition after HI improved long-term cognitive function, without impacting exploratory and locomotor activities.Conclusion: We show here that NOD1 is involved in the pathogenesis of HI-induced brain injury through modulation of autophagy-related proteins and inflammatory responses. Our findings suggest that NOD1 may be a potent target for developing therapeutic strategies for treating HI-induced brain injury.Keywords: neonatal, hypoxia-ischemia, cognitive impairment, NOD1, autophagyLiu FShao MXu FRong FDove Medical Pressarticleneonatalhypoxia-ischemiacognitive impairmentnod1autophagyNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 17, Pp 2659-2669 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	neonatal hypoxia-ischemia cognitive impairment nod1 autophagy Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	neonatal hypoxia-ischemia cognitive impairment nod1 autophagy Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Liu F Shao M Xu F Rong F Inhibition of NOD1 Attenuates Neonatal Hypoxia-Ischemia Induced Long-Term Cognitive Impairments in Mice Through Modulation of Autophagy-Related Proteins
description	Fang Liu,1 Mingyu Shao,1 Feng Xu,2 Fang Rong3 1Department of Child Health Care, Zibo Central Hospital, Zibo, 255000, Shandong, People’s Republic of China; 2Department of Pediatrics, Zibo Central Hospital, Zibo, 255000, Shandong, People’s Republic of China; 3The Community Clinic of Overseas Chinese Town, Zibo Central Hospital, North Gate of Zhongrun Overseas Chinese Town, Zibo, 255000, Shandong, People’s Republic of ChinaCorrespondence: Fang RongThe Community Clinic of Overseas Chinese Town, Zibo Central Hospital, North Gate of Zhongrun Overseas Chinese Town, Zhangdian District, Zibo, 255000, Shandong, People’s Republic of ChinaTel +86-18678186178Email rongfang0817@163.comBackground: Autophagy is implicated in neonatal hypoxia-ischemia (HI) induced cognitive impairment. The nucleotide-oligomerizing domain-1 (NOD1), a protein involved in inflammatory responses, has been shown to activate autophagy to promote progression of other diseases. We aimed to investigate whether and how NOD1 is involved in HI-induced brain injury using an HI mouse model.Methods: We induced HI in neonatal mice and examined levels of NOD1 and genes associated with autophagy. We then inhibited NOD1 by intracerebroventricular injection of si-NOD1 following HI induction and tested the effects on autophagy, inflammatory responses and long-term behavioral outcomes through Morris water maze and open field tests.Results: We found that HI induction significantly elevated mRNA levels of NOD1 (3.54 folds change) and autophagy-related genes including Atg5 (3.89 folds change) and Beclin-1 (3.34 folds change). NOD1 inhibition following HI induction suppressed autophagy signaling as well as HI induced proinflammatory cytokine production. Importantly, NOD1 inhibition after HI improved long-term cognitive function, without impacting exploratory and locomotor activities.Conclusion: We show here that NOD1 is involved in the pathogenesis of HI-induced brain injury through modulation of autophagy-related proteins and inflammatory responses. Our findings suggest that NOD1 may be a potent target for developing therapeutic strategies for treating HI-induced brain injury.Keywords: neonatal, hypoxia-ischemia, cognitive impairment, NOD1, autophagy
format	article
author	Liu F Shao M Xu F Rong F
author_facet	Liu F Shao M Xu F Rong F
author_sort	Liu F
title	Inhibition of NOD1 Attenuates Neonatal Hypoxia-Ischemia Induced Long-Term Cognitive Impairments in Mice Through Modulation of Autophagy-Related Proteins
title_short	Inhibition of NOD1 Attenuates Neonatal Hypoxia-Ischemia Induced Long-Term Cognitive Impairments in Mice Through Modulation of Autophagy-Related Proteins
title_full	Inhibition of NOD1 Attenuates Neonatal Hypoxia-Ischemia Induced Long-Term Cognitive Impairments in Mice Through Modulation of Autophagy-Related Proteins
title_fullStr	Inhibition of NOD1 Attenuates Neonatal Hypoxia-Ischemia Induced Long-Term Cognitive Impairments in Mice Through Modulation of Autophagy-Related Proteins
title_full_unstemmed	Inhibition of NOD1 Attenuates Neonatal Hypoxia-Ischemia Induced Long-Term Cognitive Impairments in Mice Through Modulation of Autophagy-Related Proteins
title_sort	inhibition of nod1 attenuates neonatal hypoxia-ischemia induced long-term cognitive impairments in mice through modulation of autophagy-related proteins
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/e446a5cdbf9f4b35acc2846e02aefae9
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Inhibition of NOD1 Attenuates Neonatal Hypoxia-Ischemia Induced Long-Term Cognitive Impairments in Mice Through Modulation of Autophagy-Related Proteins

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