TGF-beta 1 expression is reduced in hydrocephalic H-Tx rat brain

Transforming growth factor-beta 1 (TGF-beta 1) is a cytokine with diverse b iological effects. Overexpression of TGF-beta 1 in mice has been shown to i nduce progressive hydrocephalus. We have used a quantitative RT-PCR method to analyze the TGF-beta 1 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 l ower TGF-beta 1 levels than their normal siblings (p < 0.01). This differen ce became insignificant in the 21-day group. Besides, both hydrocephalic an d normal H-Tx rats have significantly lower TGF-beta 1 levels in all three age groups of 3-, 10- and 21-days than SD control rats (p < 0.01 in all thr ee groups) although the difference tends to become less significant with de velopment. We also tested the expression of another cytokine, the epidermal growth factor, and observed a similar reduction. This suggests that the TG F-beta 1 expression change is not unique to the development of hydrocephalu s in this rat model; Our hypothesis is that the TCF-beta 1 expression decre ase 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 currentl y being made to test this hypothesis.