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Post-translational modifications of chromatin-bound proteins play an important role in the regulation of eukaryotic gene expression. Processes such as acetylation, methylation, phosphorylation and ADP-ribosylation may alter the interaction of these proteins with DNA and consequently affect chromatin conformation and the binding of enzymes and other molecules involved in the regulation of gene expression. In the present study the process of ADP-ribosylation of chromosomal proteins (histone and non-histone proteins) in some rat brain regions during postnatal development was investigated; also the effect of epidermal growth factor (EGF) on this process in fetal brain slices was studied. It has been found that the process of ADP-ribosylation of total histones extracted from rat cerebral cortex and cerebellum at 1, 10 and 30 days of age, increases from 1 to 10 days of age (i.e. the period of maximal cell proliferation) and decreases thereafter, while the process of ADP-ribosylation of non-histone proteins (NHPs) sharply decreases during the same developmental period. The addition of EGF to fetal brain slices causes a significant increase of ADP-ribosylation of total histones (particularly of the histone H1 fraction) and also of NHPs and microsomal proteins. This result is in agreement with the effect of EGF as a mitogen factor, previously shown in astroglial cell cultures.

Results of experiments in cell cultures suggested that epidermal growth factor might influence an early stage of astroglial or neuronal cell differentiation. In order to evaluate this hypothesis the effects of subcutaneous and intracerebral treatment with epidermal growth factor on glutamine synthetase, an astroglial marker enzyme, and glutamate decarboxylase activity, a marker enzyme of GABAergic neurons, were investigated during postnatal development of mouse brain. Epidermal growth factor, at the dose used, induced the well-known effects of the in vivo treatment, such as a decrease in body weight and a precocious incisor eruption and eyelid opening. A decrease in forebrain and cerebellum wet weight was also observed. However, repeated epidermal growth factor treatment, during early postnatal life, failed to influence glutamine synthetase activity in forebrain or cerebellum, while a significant decrease was observed in the brain stem. No effect of epidermal growth factor on forebrain glutamate decarboxylase activity was observed. Although epidermal growth factor receptors have been detected in the newborn rodent brain, the role of this growth factor in brain development remains to be elucidated.