TY - JOUR
T1 - Combined effects of aquaporin-4 and hypoxia produce age-related hydrocephalus
AU - Trillo-Contreras, José Luis
AU - Ramírez-Lorca, Reposo
AU - Hiraldo-González, Laura
AU - Sánchez-Gomar, Ismael
AU - Galán-Cobo, Ana
AU - Suárez-Luna, Nela
AU - Sánchez de Rojas-de Pedro, Eva
AU - Toledo-Aral, Juan José
AU - Villadiego, Javier
AU - Echevarría, Miriam
N1 - Funding Information:
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.
Funding Information:
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.
Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/10
Y1 - 2018/10
N2 - 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.
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.
KW - AQP4
KW - Aging
KW - Cerebrospinal fluid
KW - Hydrocephalus
KW - Hypoxia
KW - Mice
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UR - http://www.scopus.com/inward/citedby.url?scp=85051101133&partnerID=8YFLogxK
U2 - 10.1016/j.bbadis.2018.08.006
DO - 10.1016/j.bbadis.2018.08.006
M3 - Article
C2 - 30293570
AN - SCOPUS:85051101133
SN - 0925-4439
VL - 1864
SP - 3515
EP - 3526
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 10
ER -