Diabetes-related changes in rat cerebral occludin and zonula occludens-1 (ZO-1) expression.

The endothelial or epithelial tight junctions create a barrier to diffusion of solutes. Since experimental diabetes mellitus is associated with considerable alterations in the blood-brain barrier (BBB), it is possible that specific tight junction proteins may be altered in diabetes. To test this hypothesis, Western and Northern blot analysis were carried out to measure the steady-state level of occludin and zonula occludens-one (ZO-1) proteins and mRNA levels in cerebral tissue of streptozotocin-induced diabetic rats and the results were compared to insulin treated diabetic rats and vehicle injected control rats. The cerebral occludin content in diabetic rats (115.4 +/- 18.6 arbitrary units) was significantly reduced compared to insulin-treated diabetic rats (649.1 +/- 141.2) or control rats (552.9 +/- 82.9), p < 0.001. The ZO-1 content of cerebral tissue from diabetic rats (1,240.6 +/- 199.7 arbitrary units) was not significantly altered compared to controls (1,310.8 +/- 256.9). The cerebral occludin mRNA content relative to G3PDH mRNA was 1.35 +/- 0.07 and 1.34 +/- 0.19 in control and diabetic rats respectively. The cerebral ZO-1 mRNA content relative to G3PDH mRNA in diabetic and control rats was 1.135 +/- 0.123 and 0.956 +/- 0.038 respectively. These differences did not achieve statistical significance. It is concluded that diabetes alters the molecular anatomy of the tight junctions in cerebral tissue by altering the content of select structural proteins.