Reference - Detail
|Author||Liu J, Wang H, Zhang L, Xu Y, Deng W, Zhu H, Qin C.|
|Title||S100B transgenic mice develop features of Parkinson's disease.|
|Journal||Arch. Med. Res.|
BACKGROUND AND AIMS:Parkinson's disease (PD) is one of the most common neurodegenerative disorders. Until now, the cause and mechanism of PD are unknown, making further studies necessary. We undertook this study to establish the brain-specific S100B gene transgenic mice and investigate the role of S100B in the development of PD.
METHODS:The hS100B transgenic vector was constructed by inserting the human S100B gene downstream into platelet-derived growth factor (PDGF) promoter, followed by microinjection to produce transgenic mice. Motor coordination ability of mice in the S100B transgenic group (TG), S100B knockout group (KG) and the non-transgenic control group (CG) were measured by the Rota-rod test. The expressions of dopamine D1 receptor (D1DR), dopamine D2 receptor (D2DR), G protein-coupled receptor kinase2 (GRK2), G protein-coupled receptor kinase5 (GRK5), tyrosine hydroxylase (TH) in the brain tissue, and levels of dioxyphenylalanine (DOPA), dopamine (DA), homovanillic acid (HVA), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in the midbrain tissue were detected by RT-PCR, Western blotting, and high-performance liquid chromatography-fluorescence detection method (HPLC-FLD), respectively.
RESULTS:Compared with CG, in TG, the motor coordination ability of mice, expressions of D2DR and GRK2, and the level of 5-HT visibly decreased, while the levels of DOPA, DA and its metabolic product HVA increased, the expressions of D1DR, GRK5, TH and 5-HIAA were similar. Compared with CG, no obvious change of detection indexes was observed in KG.
CONCLUSIONS:Overexpression of S100B in the brain resulted in motor coordination impairment, which may have resulted from the downregulation of D2DR and GRK2 expressions, increased DA synthesis and metabolism, and decreased 5-HT level. Therefore, S100B may be a potential cause of pathogenesis in PD.
|MeSH||Animals Brain / anatomy & histology Brain / metabolism Dopamine / metabolism G-Protein-Coupled Receptor Kinase 2 / genetics G-Protein-Coupled Receptor Kinase 2 / metabolism G-Protein-Coupled Receptor Kinase 5 / genetics G-Protein-Coupled Receptor Kinase 5 / metabolism Homovanillic Acid / metabolism Humans Hydroxyindoleacetic Acid / metabolism Mice Mice, Inbred C57BL Mice, Transgenic* Motor Activity / physiology Nerve Growth Factors / genetics* Nerve Growth Factors / metabolism Parkinson Disease / genetics Parkinson Disease / pathology* Parkinson Disease / physiopathology* Phenylalanine / chemistry Phenylalanine / metabolism Platelet-Derived Growth Factor / genetics Psychomotor Performance / physiology Receptors, Dopamine D1 / genetics Receptors, Dopamine D1 / metabolism Receptors, Dopamine D2 / genetics Receptors, Dopamine D2 / metabolism Rotarod Performance Test S100 Calcium Binding Protein beta Subunit S100 Proteins / genetics* S100 Proteins / metabolism Serotonin / metabolism|
|WOS Category||MEDICINE, RESEARCH & EXPERIMENTAL|