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 unilateral 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 expression of platelet-derived growth factor A- and B-chain proteins was analysed by enzyme-linked immunosorbent assay and immunohistochemistry. 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 observation period of four weeks. In the substantia nigra ipsilateral to the lesion, a strongly increased level of B-chain and, to a lesser extent, of A-chain messenger RNA was already detected at 4h, reaching a maximal level at one day. No significant increase was seen either in sham-operated rats or in the contralateral striatum and substantia nigra. Amounts of platelet-derived growth factor proteins were examined separately by enzyme-linked immunosorbent assay in both sides of the substantia nigra, striatum and cortex. Three days after 6-hydroxydopamine lesions the levels of both platelet-derived growth factor A- and B-chains increased in the ipsilateral striatum, substantia nigra, and cortex. An increase in the A-chain was also observed in the contralateral side of the brain. The signal for brain-derived neurotrophic factor messenger RNA increased in the striatum in the lesioned side and, to a lesser 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-derived growth factor-producing cells were neurons. In summary, we have shown that platelet-derived growth factor messenger RNA as well as its protein are induced after injury to dopaminergic cells. These data indicate an important role of platelet-derived growth factor in the dopaminergic system.
Funa
K
K
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
Yamada
N
N
Brodin
G
G
Pietz
K
K
Ahgren
A
A
Wictorin
K
K
Lindvall
O
O
Odin
P
P
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007839:Functional Laterality; D007700:Kinetics; D009928:Organ Specificity; D016627:Oxidopamine; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology; D014158:Transcription, Genetic
D019208:Brain-Derived Neurotrophic Factor; D017931:DNA Primers; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D016627:Oxidopamine