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The endothelial or epithelial tight junctions create a rate-limiting barrier to diffusion of solutes. A major determinant of the barrier function is the density of tight junction proteins. Since aging is associated with significant alterations in the blood-brain barrier (BBB) it is possible that specific tight junction proteins may be altered in the cerebrum of aging rats. 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 their mRNA in cerebral tissue of 3-, 12- and 24-month-old rats. The cerebral occludin content in 24-month-old rats (732.5+/-99.9 arbitrary units) was significantly reduced compared to 12-month-old rats (1043.4+/-131.8) or 3-month-old rats (1021.4+/-62.8), P<0.01. The cerebral ZO-1 protein content in 24-month-old rats (161.7+/-8.1 arbitrary units) and 12-month-old rats (144.3+/-35.9) were not significantly reduced compared to 4-month-old rats (189.0+/-27.2). The occludin mRNA content relative to G3PDH mRNA was 1.11+/-0.05, 1.11+/-0.07 and 1.00+/-0.05 in 3-, 12- and 24-month-old rats, respectively. The differences did not achieve statistical significance. The ZO-1 mRNA content of cerebral tissue relative to G3PDH mRNA was significantly increased in 24-month-old rats compared to 3-month-old rats (1.280+/-0.030 vs. 0.956+/-0.038), P<0.001. It is concluded that aging in rats may alter the molecular anatomy of the BBB by altering the content of select structural proteins of tight junctions.

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.