Enhanced synthesis of platelet-derived growth factor following injury induced by 6-hydroxydopamine in rat brain

• Published in: Neuroscience Vol. 74; no. 3; pp. 825 - 833
• Main Authors: Funa, K, Yamada, N, Brodin, G, Pietz, K, Åhgren, A, Wictorin, K, Lindvall, O, Odin, P
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-10-1996; Elsevier
• Subjects: Animals; BDNF; Biochemistry and metabolism; Biological and medical sciences; Brain-Derived Neurotrophic Factor - biosynthesis; Central nervous system; Cerebral Cortex - metabolism; Cerebral Cortex - pathology; Corpus Striatum - metabolism; Corpus Striatum - pathology; DNA Primers; dopaminergic neuron; Enzyme-Linked Immunosorbent Assay; Female; Functional Laterality; Fundamental and applied biological sciences. Psychology; immunohistochemistry; Kinetics; lesion; Organ Specificity; Oxidopamine; Platelet-Derived Growth Factor - biosynthesis; Polymerase Chain Reaction; rat; Rats; Rats, Sprague-Dawley; RNA, Messenger - biosynthesis; Substantia Nigra - metabolism; Substantia Nigra - pathology; Transcription, Genetic; Vertebrates: nervous system and sense organs; BSA, bovine serum albumin; GADPH, glyceraldehyde-3-phosphate dehydrogenase; rat; SN, substantia nigra; BDNF; EGF, epidermal growth factor; FGF, fibroblast growth factor; dopaminergic neuron; ELISA, enzyme-linked immunosorbent assay; 6-OHDA, 6-hydroxydopamine; BDNF, brain-derived neurotrophic factor; GDNF, glial cell line-derived neurotrophic factor; RT-PCR, reverse transcription–polymerase chain reaction; DA, dopaminergic; TGF, transforming growth factor; TH, tyrosine hydroxylase; enzyme-linked immunosorbent assay; ANOVA, analysis of variance; EDTA, ethylenediaminetetraacetate; PCR, polymerase chain reaction; immunohistochemistry; IGF, insulin-like growth factor; PDGF, platelet-derived growth factor; lesion; Vertebrata; Mammalia; Rat; Rodentia; Central nervous system; Dopaminergic neuron; Biosynthesis; Brain derived neurotrophic factor; Lesion; Oxidopamine; Platelet derived growth factor; Brain (vertebrata)
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/0306-4522(96)00152-2

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 4
h, 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 the 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.