RT Journal Article
T1 Combined effects of aquaporin-4 and hypoxia produce age-related hydrocephalus.
A1 Trillo-Contreras, Jose Luis
A1 Ramirez-Lorca, Reposo
A1 Hiraldo-Gonzalez, Laura
A1 Sanchez-Gomar, Ismael
A1 Galan-Cobo, Ana
A1 Suarez-Luna, Nela
A1 Sanchez-de-Rojas-de-Pedro, Eva
A1 Toledo-Aral, Juan Jose
A1 Villadiego, Javier
A1 Echevarria, Miriam
K1 AQP4
K1 Aging
K1 Cerebrospinal fluid
K1 Hydrocephalus
K1 Hypoxia
K1 Mice
AB Aquaporin-4, present in ependymal cells, in glia limiting and abundantly in pericapillary astrocyte foot processes, 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.
PB Eselvier BV
SN 0925-4439
YR 2018
FD 2018-08-08
LK http://hdl.handle.net/10668/13039
UL http://hdl.handle.net/10668/13039
LA en
NO Trillo-Contreras JL, Ramírez-Lorca R, Hiraldo-González L, Sánchez-Gomar I, Galán-Cobo A, Suárez-Luna N, et al. Combined effects of aquaporin-4 and hypoxia produce age-related hydrocephalus. Biochim Biophys Acta Mol Basis Dis. 2018 Oct;1864(10):3515-3526.
NO This study has been supported by grants FIS: PI12/01882 and PI16/00493 from the Spanish Ministry of Economy and Competitiveness, co-financed by the Carlos III Health Institute (ISCIII) and European Regional Development Fund (FEDER). JLTC was partially supported by the Regional Government of Andalusia and FEDER funds through a program for recruitment of young researchers.
DS RISalud
RD Apr 12, 2025