PMID:30293570

Citation	Trillo-Contreras, JL, Ramírez-Lorca, R, Hiraldo-González, L, Sánchez-Gomar, I, Galán-Cobo, A, Suárez-Luna, N, Sánchez de Rojas-de Pedro, E, Toledo-Aral, JJ, Villadiego, J and Echevarría, M (2018) Combined effects of aquaporin-4 and hypoxia produce age-related hydrocephalus. Biochim Biophys Acta Mol Basis Dis 1864:3515-3526
Abstract	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.
Links	PubMed Online version:10.1016/j.bbadis.2018.08.006
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:AQP4		GO:0021591: ventricular system development	ECO:0000315:		P		Figure 3 shows that AQP4 plays a key role in filling the ventricles with cerebrospinal fluid. Supplemental Material 4B shows that this was not a result of the systematic arterial blood pressure and that it can be inferred that it is caused by AQP4.	complete CACAO 13362
MOUSE:AQP4		GO:0033326: cerebrospinal fluid secretion	ECO:0000315:		P		Figure 5 shows that higher levels of APQ4 can lead to an overloading of CSF in the ventricles since the CSF is not able to flow out of the ventricles. This increases pressure in the ventricles. Aquaporin-4 as found in uniprot, and AQP4 Mus musculus (Mouse)	complete CACAO 13364

References

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