Abstract text (incl. figure legends and references)

Question

Idiopathic intracranial hypertension (IIH) is a disease characterized by an elevated intracranial pressure (ICP). As IIH predominantly occurs in obese women in the reproductive age it has been hypothesized that an altered hormonal composition could affect the activity of transporters involved in cerebrospinal fluid (CSF) secretion, thus affecting ICP. We aimed to investigate if gene expression of various transporters involved in CSF secretion at choroid plexus (CP) were different between males and females and between females in different estrous cycle states.

Method

10 metestrus (MET), 10 estrous (ES) and 10 male, all Sprague Dawley rats (11-13 weeks) were used. Female rats during MET have higher hormonal levels compared to ES. The estrous cycle stage was determined by wet vaginal smear and microscopy before euthanasia. CP from lateral and 4th ventricles were collected. CP was subjected to RT-qPCR analysis.

Results

We found difference between males and females during estrous cycle stage. Gene expression of the water transporter Aqp1 was higher in males compared to ES females (P<0.01). Expression of the gene encoding for NKCC1 (water transporter) and carbonic anhydrase II was higher in males and MET females compared to ES females (P<0.0001). Further, the gene encoding for carbonic anhydrase III was lower in males and MET females compared to ES females (P<0.05). Furthermore, when comparing gene expression in females at different cycle states the expression of sodium-bicarbonate cotransporter, NBCe2, were higher in MET females compared to ES females (P<0.05). There were no differences in expression of Aqp4 and NCBE.

Conclusion

This study demonstrates that gene expression at CP is affected by the estrous cycle in rats. Further, expression of some transporters was sex-dependent during estrous stage. This opens the possibility that the expression of transporters involved in CSF may be regulated by hormones and be linked to the pathophysiology of IIH.