Examination of a hypothesis that thining of the cerebral cortex in congenital hydrocephalus is caused by delayd neuronal differentiation

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We examined whether aberrant expression of neurotrophic factors and delayd neurinal differentiation occurs in congenital hydrocephalus HTX rats. HTX rats were sacrificed at postnatal day 3 (P3) and day 6 (P6), and immunohistochemical analysis was conducted to see localization and expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and receptor TrkB.Wistar rats were used for controls.The cerebral cortex : NGF were hardly immunostained in both HTX and Wistar rat groups. BDNF were diffusely stained in all the cerebral cortex in controls, while in HTX rats the immunoreactivity was observed only in the 2nd and 3rd layrs where strongly stained and faintly stained cells were intermingled. NT-3 were stained difusely in the cytoplasm of the cell in controls but in the nucleus in HTX rats. This finding in HTX rats was observed in the earlier stage of control rats, suggesting that neuronal differentiation may be delayd in HTX rats. Expression of TrkB were less in HTX rats compared to controls.The hippocampus : Immunostaining of NGF,similar to the finding in the cerebral cortex, was hardly detected in either control or HTX rats. BDNF was stained in the stratum radiatum and the oriens layr in both groups. Its immunoreactivity in controls decreased as the development proceeded, however, in HTX rats was still strong at P6, suggesting the delayd neuronal differentiation in HTX rats. NT-3 was immunostained in the oriens layr, and the reactivity was similar in both groups. In the pyramidal layrs, all the three neurotrophic factors did not show any difference between the two groups.Some results in this study suggest that neuronal differentiation may be delayd in congenital hydrocephalus HTX rats. To confirm those immunohistochemical findings, we are now conducting the quantitative analysis with RT-PCR.