TGF-beta1 expression is reduced in hydrocephalic H-Tx rat brain

Transforming growth factor-beta1 (TGF-beta1) is a cytokine with diverse biological effects. Overexpression of TGF-beta1 in mice has been shown to induce progressive hydrocephalus. We have used a quantitative RT-PCR method to analyze the TGF-beta1 expression in the brains of H-Tx rat, a model of congenital hydrocephalus. Our studies have shown that rather than increased expression, the 3- and 10-day hydrocephalic H-Tx rats have significantly lower TGF-beta1 levels than their normal siblings (p < 0.01). This difference became insignificant in the 21-day group. Besides, both hydrocephalic and normal H-Tx rats have significantly lower TGF-beta1 levels in all three age groups of 3-, 10- and 21-days than SD control rats (p < 0.01 in all three groups) although the difference tends to become less significant with development. We also tested the expression of another cytokine, the epidermal growth factor, and observed a similar reduction. This suggests that the TGF-beta1 expression change is not unique to the development of hydrocephalus in this rat model. Our hypothesis is that the TGF-beta1 expression decrease in the H-Tx rat is not the cause of the disease. Rather it might be the result of feedback inhibition by increase in the expression of the gene it regulates, including an extracellular matrix component. Effort is currently being made to test this hypothesis.