Preconditioning in hypoxic-ischemic neonate mice triggers Na+-Ca2+ exchanger-dependent neurogenesis

Abstract To identify alternative interventions in neonatal hypoxic-ischemic encephalopathy, researchers’ attention has been focused to the study of endogenous neuroprotective strategies. Based on the preconditioning concept that a subthreshold insult may protect from a subsequent harmful event, we a...

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Main Authors: P. Brancaccio, S. Anzilotti, O. Cuomo, A. Vinciguerra, M. Campanile, A. Herchuelz, S. Amoroso, L. Annunziato, G. Pignataro
Format: Article
Language:English
Published: Nature Publishing Group 2022-07-01
Series:Cell Death Discovery
Online Access:https://doi.org/10.1038/s41420-022-01089-z
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author P. Brancaccio
S. Anzilotti
O. Cuomo
A. Vinciguerra
M. Campanile
A. Herchuelz
S. Amoroso
L. Annunziato
G. Pignataro
author_facet P. Brancaccio
S. Anzilotti
O. Cuomo
A. Vinciguerra
M. Campanile
A. Herchuelz
S. Amoroso
L. Annunziato
G. Pignataro
author_sort P. Brancaccio
collection DOAJ
description Abstract To identify alternative interventions in neonatal hypoxic-ischemic encephalopathy, researchers’ attention has been focused to the study of endogenous neuroprotective strategies. Based on the preconditioning concept that a subthreshold insult may protect from a subsequent harmful event, we aimed at identifying a new preconditioning protocol able to enhance Ca2+-dependent neurogenesis in a mouse model of neonatal hypoxia ischemia (HI). To this purpose, we also investigated the role of the preconditioning-linked protein controlling ionic homeostasis, Na+/Ca2+ exchanger (NCX). Hypoxic Preconditioning (HPC) was reproduced by exposing P7 mice to 20’ hypoxia. HI was induced by isolating and cutting the right common carotid artery. A significant reduction in ischemic damage was observed in mice subjected to 20’ hypoxia followed,3 days later, by 60’ HI, thus suggesting that 20’ hypoxia functions as preconditioning stimulus. HPC promoted neuroblasts proliferation in the dentate gyrus mirrored by an increase of NCX1 and NCX3-positive cells and an improvement of behavioral motor performances in HI mice. An attenuation of HPC neuroprotection as well as a reduction in the expression of neurogenesis markers, including p57 and NeuroD1, was observed in preconditioned mice lacking NCX1 or NCX3. In summary, PC in neonatal mice triggers a neurogenic process linked to ionic homeostasis maintenance, regulated by NCX1 and NCX3.
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spelling doaj.art-9338721e5fd94e80bbeb195015bc2db32022-12-22T03:01:07ZengNature Publishing GroupCell Death Discovery2058-77162022-07-018111110.1038/s41420-022-01089-zPreconditioning in hypoxic-ischemic neonate mice triggers Na+-Ca2+ exchanger-dependent neurogenesisP. Brancaccio0S. Anzilotti1O. Cuomo2A. Vinciguerra3M. Campanile4A. Herchuelz5S. Amoroso6L. Annunziato7G. Pignataro8Division of Pharmacology, Department of Neuroscience, School of Medicine, University of Naples “Federico II”Department of Science and Technology, University of SannioDivision of Pharmacology, Department of Neuroscience, School of Medicine, University of Naples “Federico II”Department of Biomedical Sciences and Public Health, School of Medicine, University “Politecnica delle Marche”Division of Pharmacology, Department of Neuroscience, School of Medicine, University of Naples “Federico II”Laboratoire de Pharmacodynamie et de Therapeutique—Faculté de Médecine Université Libre de BruxellesDepartment of Biomedical Sciences and Public Health, School of Medicine, University “Politecnica delle Marche”IRCCS Synlab SDN S.p.A, via Gianturco 113Division of Pharmacology, Department of Neuroscience, School of Medicine, University of Naples “Federico II”Abstract To identify alternative interventions in neonatal hypoxic-ischemic encephalopathy, researchers’ attention has been focused to the study of endogenous neuroprotective strategies. Based on the preconditioning concept that a subthreshold insult may protect from a subsequent harmful event, we aimed at identifying a new preconditioning protocol able to enhance Ca2+-dependent neurogenesis in a mouse model of neonatal hypoxia ischemia (HI). To this purpose, we also investigated the role of the preconditioning-linked protein controlling ionic homeostasis, Na+/Ca2+ exchanger (NCX). Hypoxic Preconditioning (HPC) was reproduced by exposing P7 mice to 20’ hypoxia. HI was induced by isolating and cutting the right common carotid artery. A significant reduction in ischemic damage was observed in mice subjected to 20’ hypoxia followed,3 days later, by 60’ HI, thus suggesting that 20’ hypoxia functions as preconditioning stimulus. HPC promoted neuroblasts proliferation in the dentate gyrus mirrored by an increase of NCX1 and NCX3-positive cells and an improvement of behavioral motor performances in HI mice. An attenuation of HPC neuroprotection as well as a reduction in the expression of neurogenesis markers, including p57 and NeuroD1, was observed in preconditioned mice lacking NCX1 or NCX3. In summary, PC in neonatal mice triggers a neurogenic process linked to ionic homeostasis maintenance, regulated by NCX1 and NCX3.https://doi.org/10.1038/s41420-022-01089-z
spellingShingle P. Brancaccio
S. Anzilotti
O. Cuomo
A. Vinciguerra
M. Campanile
A. Herchuelz
S. Amoroso
L. Annunziato
G. Pignataro
Preconditioning in hypoxic-ischemic neonate mice triggers Na+-Ca2+ exchanger-dependent neurogenesis
Cell Death Discovery
title Preconditioning in hypoxic-ischemic neonate mice triggers Na+-Ca2+ exchanger-dependent neurogenesis
title_full Preconditioning in hypoxic-ischemic neonate mice triggers Na+-Ca2+ exchanger-dependent neurogenesis
title_fullStr Preconditioning in hypoxic-ischemic neonate mice triggers Na+-Ca2+ exchanger-dependent neurogenesis
title_full_unstemmed Preconditioning in hypoxic-ischemic neonate mice triggers Na+-Ca2+ exchanger-dependent neurogenesis
title_short Preconditioning in hypoxic-ischemic neonate mice triggers Na+-Ca2+ exchanger-dependent neurogenesis
title_sort preconditioning in hypoxic ischemic neonate mice triggers na ca2 exchanger dependent neurogenesis
url https://doi.org/10.1038/s41420-022-01089-z
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