Abstract

Though diabetes is a disease with vascular complications, little is known about its effects on the blood-brain barrier or the blood-cerebrospinal fluid barrier (BCSFB). The BCSFB is situated at choroid plexuses located in the lateral, third, and fourth ventricles. Choroid plexuses are the primary site of cerebrospinal fluid (CSF) production and express numerous ion transporters. Previous studies have shown a perturbation of ion transport in the periphery and brain during diabetes. In this study, we investigated the effect of diabetes on ion transporters in the choroid plexuses of streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in male Sprague-Dawley rats by intraperitoneal injection of STZ (60 mg/kg in citrate buffer, confirmed by glucose analysis: 601 ± 22 mg/dl diabetic rats, 181 ± 46 mg/dl age-matched controls); and at 28 days, rats were killed, choroid plexuses harvested, and protein extracted. Western blot analyses were carried out using antibodies for ion transporters, including Na⁺-K⁺-2Cl⁻ cotransporter and the Na⁺-K⁺-ATPase α1-subunit. The efflux of the K⁺ analog ⁸⁶Rb⁺ from choroid plexus was also studied. Diabetic rats showed an increase in expression of the Na⁺-K⁺-2Cl⁻ cotransporter and the Na⁺-K⁺-ATPase α1-subunit, as compared with age-matched controls, a decrease in Na⁺-H⁺ exchanger expression, and no change in Na⁺-K⁺-ATPase β1- or β2-subunit. The net effect of these changes was a 66% increase in ⁸⁶Rb⁺ efflux from diabetic choroid plexus compared with controls. These changes in expression may affect choroid plexus ion balance and thus significantly affect CSF production in diabetic rats.