Expression of aquaporin 4 (AQP4) in postmortem human brain cortex of subjects with different psychiatric disorders

Abstract

Aquaporins are specialized water transport channels expressed in plasma membranes of water-permeable tissues that maintain water and ion homeostasis. Aquaporins 1 and 4 (AQP1 and AQP4) are the most important to fluid movements in mammalian brain. AQP4 has been implicated in the generation of brain edema, astrocyte migration, and in the control of neuronal excitability. These and other studies have turned it into an important drug target for treatment of diseases such as cerebral edema, mesial temporal lobe epilepsy, and a variant of multiple sclerosis. Moreover, over-expression changes of the gene coding for the AQP4 have been associated with bipolar disorder and major depression, and it has been described as necessary for the antidepressive action of fluoxetine. The aim of this study was to evaluate the immunoreactive protein density of AQP4 in postmortem prefrontal cortex samples of subjects with a previous diagnosis of three different mental disorders: major depression (MD, n=15), bipolar disorder (BD, n=19) and schizophrenia (SCH, n=22). Three groups of matched controls for gender, age and postmortem delay were included. Additionally, a group of suicide victims (n=12) with no previous diagnosis of mental disorder was also included. The immunodensities of the two isoforms of AQP4 (34 and 32 kDa) and beta-actin (used as internal control) were detected simultaneously by using specific primary and fluorescent secondary antibodies. The density of AQP1 was also quantified. All bands were quantified by densitometry and the relative density levels were normalized and expressed as a percentage of control samples. An increase of the density of the two AQP4 isoforms was detected in MD, BD, and SCH groups, while no changes were detected in the case of suicide. These changes were statistically significant for both the 32 and 34 kDa isoforms in BD (34 kDa: 118%, p<0.05; 32 kDa: 124%, p<0.05) and SCH (34 kDa: 130%, p<0.05; 32 kDa: 153%, p<0.05), and only for the 34 kDa in MD (34 kDa: 132%, p< 0.01). When the immunodensity of AQP1 was tested in the same sample groups, a statistically significant increase in MD (150%, p<0.05) and BD (168%, p<0.05) over their respective control groups was detected, while no change was observed (95%, p>0.05) in SCH and suicide (91%, p>0.05) groups. These results suggests an implication of aquaporins in neuropsychiatric disorders.