Aquaporins in the brain: from aqueduct to “multi-duct”
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The aquaporin channel family was first considered as a family of water channels, however it is now clear that some of these channels are also permeable to small solutes such glycerol, urea and monocarboxylates. In this review, we will consider AQP4 and AQP9 expressed in the rodent brain. AQP4 is present on astrocytic end-feet in contact with brain vessels and could be involved in ionic homeostasis. However, AQP4 may also be involved in cell adhesion. AQP4 expression is highly modified in several brain disorders and it can play a key role in the cerebral edema formation. However, the exact role of AQP4 in edema formation is still debated. Recently, AQP4 has been shown to be also involved in astrocyte migration during glial scar formation. AQP9 is expressed in astrocytes and in catecholaminergic neurons. Two isoforms of AQP9 are expressed in brain cells, the shortest isoform is localized in the inner membrane of mitochondria and the longest in the cell membrane. The level of expression of AQP9 is negatively regulated by high concentrations of insulin. Taken together, these results suggest that AQP9 could be involved in brain energy metabolism. The induction of AQP9 in astrocytes is observed with time after stroke onset suggesting participation in the clearance of excess lactate in the extracellular space. These recent exciting results suggest that AQPs may not only be involved in water homeostasis in the brain but could also participate in other important physiological functions.
KeywordsWater channel Glycerol Lactate Catecholaminergic neurons Edema Ischemia
The authors wish thank Dr M. Price for critical comments on the manuscript. This study was supported by grants from the Swiss Science Foundation (FN 3100AO-108001); Fondazione Per Lo Studio Delle Malattie Neurodegenerative Delle Persone Adulte e Dell’ Anziano”, from Lugano, Switzerland; SwissHeart foundation.
- Amiry-Moghaddam M, Otsuka T, Hurn PD, Traystman RJ, Haug FM, Froehner SC, Adams ME, Neely JD, Agre P, Ottersen OP, Bhardwaj A (2003a) An alpha-syntrophin-dependent pool of AQP4 in astroglial end-feet confers bidirectional water flow between blood and brain. Proc Natl Acad Sci U S A 100:2106–2111PubMedCrossRefGoogle Scholar
- Amiry-Moghaddam M, Williamson A, Palomba M, Eid T, de Lanerolle NC, Nagelhus EA, Adams ME, Froehner SC, Agre P, Ottersen OP (2003b) Delayed K+clearance associated with aquaporin-4 mislocalization: phenotypic defects in brains of alpha-syntrophin-null mice. Proc Natl Acad Sci U S A 100:13615–13620PubMedCrossRefGoogle Scholar
- Amiry-Moghaddam M, Xue R, Haug FM, Neely JD, Bhardwaj A, Agre P, Adams ME, Froehner SC, Mori S, Ottersen OP (2004) Alpha-syntrophin deletion removes the perivascular but not endothelial pool of aquaporin-4 at the blood-brain barrier and delays the development of brain edema in an experimental model of acute hyponatremia. FASEB J 18:542–544PubMedGoogle Scholar
- Amiry-Moghaddam M, Lindland H, Zelenin S, Roberg BA, Gundersen BB, Petersen P, Rinvik E, Torgner IA, Ottersen OP (2005) Brain mitochondria contain aquaporin water channels: evidence for the expression of a short AQP9 isoform in the inner mitochondrial membrane. FASEB J 19:1459–1467PubMedCrossRefGoogle Scholar
- Arima H, Yamamoto N, Sobue K, Umenishi F, Tada T, Katsuya H, Asai K (2003) Hyperosmolar mannitol stimulates expression of aquaporin 4 and 9 through a p38 mitogen activated protein kinase-dependent pathway in rat astrocytes. J Biol Chem 27:27Google Scholar
- Eid T, Lee TS, Thomas MJ, Amiry-Moghaddam M, Bjornsen LP, Spencer DD, Agre P, Ottersen OP, de Lanerolle NC (2005) Loss of perivascular aquaporin 4 may underlie deficient water and K + homeostasis in the human epileptogenic hippocampus. Proc Natl Acad Sci U S A 102:1193–1198PubMedCrossRefGoogle Scholar
- Frykholm P, Hillered L, Langstrom B, Persson L, Valtysson J, Watanabe Y, Enblad P (2001) Increase of interstitial glycerol reflects the degree of ischaemic brain damage: a PET and microdialysis study in a middle cerebral artery occlusion-reperfusion primate model. J Neurol Neurosurg Psychiatry 71:455–461PubMedCrossRefGoogle Scholar
- Ke C, Poon WS, Ng HK, Lai FM, Tang NL, Pang JC (2002) Impact of experimental acute hyponatremia on severe traumatic brain injury in rats: influences on injuries, permeability of blood-brain barrier, ultrastructural features, and aquaporin-4 expression. Exp Neurol 178:194–206PubMedCrossRefGoogle Scholar
- Kuriyama H, Shimomura I, Kishida K, Kondo H, Furuyama N, Nishizawa H, Maeda N, Matsuda M, Nagaretani H, Kihara S, Nakamura T, Tochino Y, Funahashi T, Matsuzawa Y (2002) Coordinated regulation of fat-specific and liver-specific glycerol channels, aquaporin adipose and aquaporin 9. Diabetes 51:2915–2921PubMedCrossRefGoogle Scholar
- Pappius HM (1974) Part I: tumors of the brain and skull. In: Vinken PJ, Bruyn GW (eds) Handbook of clinical neurology, vol. 16. North Holland Publishing Company, New York, pp 167–185Google Scholar
- Vajda Z, Pedersen M, Fuchtbauer EM, Wertz K, Stodkilde-Jorgensen H, Sulyok E, Doczi T, Neely JD, Agre P, Frokiaer J, Nielsen S (2002) Delayed onset of brain edema and mislocalization of aquaporin-4 in dystrophin-null transgenic mice. Proc Natl Acad Sci U S A 99:13131–13136PubMedCrossRefGoogle Scholar