Abstract
Aquaporins (AQPs) are water channel molecules that allow the passage of water through the lipid bilayers of cell membranes. AQP1, AQP4 and AQP9 are expressed in the central nervous system and AQP4 is well known as the target of auto-antibodies in Devic’s neuromyelitis optica. The role of AQPs in facilitating water movements suggests a link with oedema formation and resolution in the brain. Furthermore, AQPs are also involved in process formation in glial cells with a close link to neuroinflammation. This mini-review gives an overview of what is currently known about the role of AQPs in different neurological disorders.
Highlights
Aquaporins came to the attention of neurologists mainly due to Devic’s syndrome, an autoimmune condition associated with anti-AQP4 antibodies found in serum
AQP4 found on astrocyte end feet, which are in contact with cerebral blood vessels, has been linked with cerebrospinal fluid (CSF) and solute movements in the perivascular space[6] and to the clearance of metabolites from the brain tissue such as ß-amyloid.[7]
Using a preconditioning paradigm of intracerebroventricular thrombin injection 24 h before ischemia to trigger endogenous neuroprotection mechanisms,[29,30] we demonstrated increased tolerance to ischemia and reduced hemispheric swelling coinciding with a further enhancement of perivascular AQP4 expression at 1 h after ischemia.[29,31]
Summary
Aquaporins came to the attention of neurologists mainly due to Devic’s syndrome, an autoimmune condition associated with anti-AQP4 antibodies found in serum. AQPs were first described by Peter Agre, an American physician and molecular biologist, while studying red blood cell membranes and the Rhesus group He discovered a red cell membrane protein, CHIP28, with homologies to proteins expressed in various tissues such as renal tubules, fruit fly brains and plant roots.[1] He went on to show this protein was a water channel, termed Aquaporin-1 (AQP1), providing an explanation for the rapid water movement through hydrophobic red cell membranes.[2] This led to the discovery of the AQP family of water channel proteins. AQP4 found on astrocyte end feet, which are in contact with cerebral blood vessels, has been linked with CSF and solute movements in the perivascular space[6] and to the clearance of metabolites from the brain tissue such as ß-amyloid.[7] It has been proposed that CSF enters the perivascular space of brain tissue around penetrating arterioles and exchanges with insterstitial fluid. AQP9 mRNA has been detected in the brains of both rodents and non-human primates, arguing in favour of AQP9 expression in the CNS.[11,16] To date, the role of AQP9 in brain is thought to be associated with brain energy metabolism[17] and astrogliosis after stroke.[18]
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