Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/4403
Title: Aquaporin-4 Mediates Permanent Brain Alterations in a Mouse Model of Hypoxia-Aged Hydrocephalus
Authors: Trillo-Contreras, José Luis
Toledo-Aral, Juan José
Villadiego, Javier
Echevarría, Miriam
metadata.dc.contributor.authoraffiliation: [Trillo-Contreras,JL; Toledo-Aral,JJ; Villadiego,J; Echevarría,M] Institute of Biomedicine of Seville-IBiS, University Hospital Virgen del Rocío, CSIC, University of Seville, Seville, Spain. [Trillo-Contreras,JL; Toledo-Aral,JJ; Villadiego,J; Echevarría,M] Department of Medical Physiology and Biophysics, University of Seville, Seville, Spain. [Toledo-Aral,JJ; Villadiego,J] Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain
Keywords: AQP4;Astrocytes;Hypoxia;Hydrocephalus;Cerebrospinal fluid;Cerebral ventricles;Homeostasis;Drainage;Acuaporina 4;Astrocitos;Hipoxia;Hidrocefalia;Líquido cefalorraquídeo;Ventrículos cerebrales;Drenaje
metadata.dc.subject.mesh: Medical Subject Headings::Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Age Factors
Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteins::Membrane Transport Proteins::Ion Channels::Porins::Aquaporins::Aquaporin 4
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Biological Markers::Biomarkers, Pharmacological
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain
Medical Subject Headings::Diseases::Animal Diseases::Disease Models, Animal
Medical Subject Headings::Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Hydrocephalus
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Histocytochemistry::Immunohistochemistry
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Magnetic Resonance Imaging
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Phenotype
Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility
Medical Subject Headings::Anatomy::Nervous System::Neuroglia::Astrocytes
Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Physiological Processes::Homeostasis
Medical Subject Headings::Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Intracranial Hypertension
Medical Subject Headings::Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Cognition
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drainage
Issue Date: 9-Sep-2021
Publisher: MDPI
Citation: Trillo-Contreras JL, Toledo-Aral JJ, Villadiego J, Echevarría M. Aquaporin-4 Mediates Permanent Brain Alterations in a Mouse Model of Hypoxia-Aged Hydrocephalus. Int J Mol Sci. 2021 Sep 9;22(18):9745
Abstract: Aquaporin-4 (AQP4) is the principal water channel in the brain being expressed in astrocytes and ependymal cells. AQP4 plays an important role in cerebrospinal fluid (CSF) homeostasis, and alterations in its expression have been associated with hydrocephalus. AQP4 contributes to the development of hydrocephalus by hypoxia in aged mice, reproducing such principal characteristics of the disease. Here, we explore whether these alterations associated with the hydrocephalic state are permanent or can be reverted by reexposure to normoxia. Alterations such as ventriculomegaly, elevated intracranial pressure, and cognitive deficits were reversed, whereas deficits in CSF outflow and ventricular distensibility were not recovered, remaining impaired even one month after reestablishment of normoxia. Interestingly, in AQP4-/- mice, the impairment in CSF drainage and ventricular distensibility was completely reverted by re-normoxia, indicating that AQP4 has a structural role in the chronification of those alterations. Finally, we show that aged mice subjected to two hypoxic episodes experience permanent ventriculomegaly. These data reveal that repetitive hypoxic events in aged cerebral tissue promote the permanent alterations involved in hydrocephalic pathophysiology, which are dependent on AQP4 expression.
URI: http://hdl.handle.net/10668/4403
metadata.dc.relation.publisherversion: https://www.mdpi.com/1422-0067/22/18/9745/htm
metadata.dc.identifier.doi: 10.3390/ijms22189745
ISSN: 1422-0067 (Online)
Appears in Collections:01- Artículos - Hospital Virgen del Rocío
01- Artículos - IBIS. Instituto de Biomedicina de Sevilla

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