Artículo
Combined effects of aquaporin-4 and hypoxia produce age-related hydrocephalus
Autor/es | Trillo Contreras, José Luis
Ramírez Lorca, Reposo Hiraldo González, Laura Sánchez Gomar, Ismael Galán-Cobo, Ana Suárez-Luna, Nela Sánchez de Rojas de Pedro, Eva Toledo Aral, Juan José Villadiego Luque, Francisco Javier Echevarría Irusta, Miriam |
Departamento | Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica |
Fecha de publicación | 2018 |
Fecha de depósito | 2024-01-18 |
Publicado en |
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Resumen | Aquaporin-4, present in ependymal cells, in glia limiting and abundantly in pericapillary astrocyte foot pro cesses, and aquaporin-1, expressed in choroid plexus epithelial cells, play an important role in cerebrospinal
fluid ... Aquaporin-4, present in ependymal cells, in glia limiting and abundantly in pericapillary astrocyte foot pro cesses, and aquaporin-1, expressed in choroid plexus epithelial cells, play an important role in cerebrospinal fluid production and may be involved in the pathophysiology of age-dependent hydrocephalus. The finding that brain aquaporins expression is regulated by low oxygen tension led us to investigate how hypoxia and elevated levels of cerebral aquaporins may result in an increase in cerebrospinal fluid production that could be associated with a hydrocephalic condition. Here we have explored, in young and aged mice exposed to hypoxia, whether aquaporin-4 and aquaporin-1 participate in the development of age-related hydrocephalus. Choroid plexus, striatum, cortex and ependymal tissue were analyzed separately both for mRNA and protein levels of aquaporins. Furthermore, parameters such as total ventricular volume, intraventricular pressure, cerebrospinal fluid outflow rate, ventricular compliance and cognitive function were studied in wild type, aquaporin-1 and aquaporin-4 knock-out animals subjected to hypoxia or normoxia. Our data demonstrate that hypoxia is involved in the development of age-related hydrocephalus by a process that depends on aquaporin-4 channels as a main route for cerebrospinal fluid movement. Significant increases in aquaporin-4 expression that occur over the course of animal aging, together with a reduced cerebrospinal fluid outflow rate and ventricular compliance, contribute to produce more severe hydrocephalus related to hypoxic events in aged mice, with a notable impairment in cognitive function. These results indicate that physiological events and/or pathological conditions presenting with cerebral hypoxia/ischemia contribute to the development of chronic adult hydrocephalus. |
Cita | Trillo Contreras, J.L., Ramírez Lorca, R., Hiraldo González, L., Sánchez Gomar, I., Galán-Cobo, A., Suárez-Luna, N.,...,Echevarría Irusta, M. (2018). Combined effects of aquaporin-4 and hypoxia produce age-related hydrocephalus. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1864 (10), 3515-3526. https://doi.org/10.1016/j.bbadis.2018.08.006. |
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