Biochimica et Biophysica Acta (BBA) - General Subjects
ReviewAquaporin and brain diseases☆,☆☆
Section snippets
Aquaporins: subgroups and expression in brain
The aquaporin (AQP) protein family is identified by six membrane spanning domains with intracellular carboxyl (C) and amino (N) termini and a molecular weight around 30 kDa. A common characteristic between all AQP is a consensus motif, Asn-Pro-Ala, which is strongly implicated to play a key role in pore formation [1]. The 13 members of the AQP family are ubiquitously distributed throughout the mammalian tissues and can be categorized into three subgroups: i) Aquaporins (AQP0, 1, 2, 4, 5, 6 and
AQP, water movement and neuroimaging
Diffusion weighted imaging (DWI), T2-weighted imaging (T2WI) and more recently diffusion tensor imaging (DTI) are used for diagnosis/prognosis in patients with brain diseases. The computed T2 value is believed to represent the water content within brain tissues; where increased T2 values correspond to water accumulation in pathological conditions [35]. The quantitative DWI parameter, the apparent diffusion coefficient (ADC), is believed to reflect water mobility within brain tissues.
Edema process: role of the AQPs
Most brain diseases (e.g. stroke, traumatic brain injury, brain tumors, brain inflammation) present the hallmark of edema, which is water accumulation resulting from brain osmotic homeostasis dysfunctions. The main consequence of edema is the swelling of the brain, which aggravates the secondary injuries such as decrease of brain perfusion. Edema has been known in the clinic and pre-clinical science for many years but the molecular and cellular events in edema formation/resolution are still
AQP4 and neuroinflammation in autoimmune and neurodegenerative diseases
Neuroinflammation starts during the acute phase after brain injury and is also present at long term and in chronic brain pathologies like multiple sclerosis (MS). Neuroinflammation is a generic term encompassing complex molecular and cellular events at the BBB among the various brain diseases and injuries [93]. In parallel to microglia activation, astrocytes become activated and play a role in the neuroinflammation process with their involvement in astrogliosis. The role of astrogliosis is
Future developments: drugs against AQP4?
As mentioned previously, there is no specific inhibitor to block the AQP4 channel and such a compound is critical for evaluating the role of AQP4 and treatment of edema. Using siRNA strategy permitted to show the potential to use a specific inhibitor of AQP4 in jTBI and the contribution of astrocytic AQP4 in neuroimaging [54], [61]. Although non-specific, a range of compounds already commercially available that may block AQP4 have been tested. Bumetanide blocks the AQP4 channel and water
Conclusions
The pattern of AQP4 expression during brain disease reveals that AQP4 is a critical component regulating water movement in edema formation and resolution. It is important to note that the role of AQP4 in edema resolution is still unclear and debated. The role of AQP4 in edema formation or resolution might depend on the physiological conditions inducing brain injury. In acute developing injuries like trauma and ischemia, the AQP4 activation pattern seems to be different from more “chronic”
Acknowledgements
A portion of this material was performed in the Loma Linda University School of Medicine Advanced Imaging and Microscopy Core (LLUSM AIM) that is supported by the National Science Foundation under Major Research Instrumentation, Division of Biological Infrastructure Grant No. 0923559 (Sean M Wilson) and the Loma Linda University School of Medicine.
The authors are grateful to Miss Justine Aussudre, INSERM U1049 Bordeaux for excellent technical help. The authors are grateful to Dr Jean-Francois
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This article is part of a Special Issue entitled Aquaporins.
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Statement of financial support: This study was supported by grants from the National Institute of Child Disorders (NICHD) R01HD061946 (JB) and Agence Nationale de la Recherche ANR-TecSan 2006-15 “NanoBioImaging”, INSERM 2011 “Precipute”, CNRS BMI 2013 “Pep-Team” and Ligue Française contre la Sclérose En Plaques (LFSEP) (KGP).