Aquaporin-4 Levels Research Articles

Testosterone up-regulates aquaporin-4 expression in cultured astrocytes.

Aquaporin-4 (AQP4) is located on astrocyte endfeet that face blood vessels in the brain and in the pia. It is thought to play a crucial role in the development of brain edema. To confirm the notion that sex steroids and dexamethasone influence brain edema through AQP4 regulation, we investigated the effects of 17beta-estradiol, testosterone, and dexamethasone on the expression of AQP4 in cultured astrocytes. Testosterone significantly up-regulated AQP4 at the level of both protein and mRNA. At a concentration of 100 nM, testosterone significantly increased AQP4 protein levels and ameliorated the osmotic fragility of astrocytes from hypoosmotic stress, suggesting that the increased levels of AQP4 facilitated the testosterone function. Moreover, this effect was attenuated by the protein kinase C activator 12-O-tetradecanoylphorbol 13-acetate, which can rapidly decrease AQP4 mRNA expression, indicating that the response was specific. These results indicate that AQP4 can alter the osmotic fragility of astrocytes and that testosterone can influence brain edema through AQP4 regulation, whereas 17beta-estradiol and dexamethasone cannot.

Heterogeneous responses of aquaporin-4 in oedema formation in a replicated severe traumatic brain injury model in rats

Aquaporin-4 (AQP4) is the most abundant water channel in the rat brain. In this study, the distribution pattern and mRNA expression levels of AQP4 were examined in a severe traumatic brain injury model by immunohistochemistry and reverse transcription-polymerase chain reaction. Oedema formation and blood–brain barrier (BBB) integrity were assessed by wet-dry weight measurements and immunostaining of endogenous IgG respectively. In the oedematous contusional cortex with impaired BBB integrity, negative immunostaining of AQP4 and down-regulation of its mRNA level were identified ( P<0.05) at 1 day post-injury, while in other oedamatous regions of the injured brain where BBB was intact, there was no significant change in the AQP4 expression level. This heterogeneous pattern of AQP4 responses can be interpreted as follows: focal brain injury (such as a contusion) with impaired BBB resulting in vasogenic oedema is associated with reduction of AQP4 expression, whereas, in cytotoxic oedema, associated with diffuse brain injury with intact BBB, changes in AQP4 expression are not significant. This study provides basic information for investigating new treatments for traumatic brain oedema.

Ontogeny of water transport in rat brain: postnatal expression of the aquaporin-4 water channel.

Brain water transport is poorly understood at the molecular level, and marked changes occur during brain development. As the aquaporin-4 (AQP4) water channel protein is abundant in brain, the expression levels and subcellular distribution of this protein were examined during postnatal development. This study focused on the cerebellum, which showed the same pattern of AQP4 development as the rest of the brain. Semiquantitative immunoblotting revealed very low levels of AQP4 in the first postnatal week. A pronounced increase was noted in the second week, from 2% of adult level at postnatal day 7 (PN7) to 25% at PN14. At PN1 and PN3 immunofluorescence microscopy revealed weak labelling, mainly in radial processes (Bergmann fibres) and at the pial surface. Between PN7 and PN14 the labelling underneath the pia showed a strong increase, and immunoreactivity also appeared around blood vessels throughout the cerebellum. High-resolution immunogold electron microscopy revealed that the subpial and perivascular labelling was restricted to glial end feet, notably to those plasma membrane domains that were apposed to the basal laminae. At no stage was there any evidence of neuronal AQP4 labelling, and AQP1, -2, -3 and -5 proteins were not detected in the neuropil. Riboprobes to AQP4 mRNA produced a particularly strong in situ hybridization signal in glial cells between PN7 and PN14, corresponding to the stage of the most rapid increase of AQP4 protein. The time course and pattern of AQP4 expression suggests that this aquaporin plays an important role in brain water and K+ homeostasis from the second week of development.