ENHANCED SYNTHESIS OF PLATELET-DERIVED GROWTH-FACTOR FOLLOWING INJURY-INDUCED BY 6-HYDROXYDOPAMINE IN RAT-BRAIN

The kinetics of platelet-derived growth factor messenger RNA synthesis in the substantia nigra and in the striatum, before and after unilate ral intranigral 6-hydroxydopamine injection, was studied and compared with that after sham operation by a quantitative reverse transcription -polymerase chain reaction. The kinetics of brain-derived neurotrophic factor messenger RNA was studied as a comparison. Furthermore, the ex pression of platelet-derived growth factor A- and B-chain proteins was analysed by enzyme-linked immunosorbent assay and immunohistochemistr y. In the ipsilateral striatum of 6-hydroxydopamine-lesioned rats, the signal density of messenger RNA for both A- and B-chains had already increased at one day and remained at an elevated level during the obse rvation period of four weeks. In the substantia nigra ipsilateral to t he lesion, a strongly increased level of B-chain and, to a lesser exte nt, of A-chain messenger RNA was already detected at 4 h, reaching a m aximal level at one day. No significant increase was seen either in sh am-operated rats or in the contralateral striatum and substantia nigra . Amounts of platelet-derived growth factor proteins were examined sep arately by enzyme-linked immunosorbent assay in both sides of the subs tantia nigra, striatum and cortex. Three days after 6-hydroxydopamine lesions the levels of both platelet-derived growth factor A- and B-cha ins increased in the ipsilateral striatum, substantia nigra, arid cort ex. An increase in the A-chain was also observed in the contralateral side of the brain. The signal for brain-derived neurotrophic factor me ssenger RNA increased in the striatum in the lesioned side and, to a l esser extent, in the contralateral side, as well as in the substantia nigra, where a significant difference was observed when compared with the contralateral side. Semiquantitative immunohistochemical analysis on the substantia nigra confirmed the enhanced platelet-derived growth factor expression, revealing that the majority of the platelet-derive d growth factor-producing cells were neurons. In summary, we have show n that platelet-derived growth factor messenger RNA as well as its pro tein are induced after injury to dopaminergic cells. These data indica te an important role of platelet-derived growth factor in the dopamine rgic system. Copyright (C) 1996 IBRO.