title: Effects of poly (ADP-ribose) polymerase inhibitor 3-aminobenzamide on blood-brain barrier and dopaminergic neurons of rats with lipopolysaccharide-induced Parkinson's disease.
abstract: Neuro-inflammation and dysfunction of blood-brain barrier play an important role in the occurrence, development, and neuronal degeneration of Parkinson's disease (PD). Studies have demonstrated that a variety of cytokines such as TNF-α and IL-1β destroy the structure and function of blood-brain barrier. The damage to blood-brain barrier results in death of dopaminergic neurons, while protection of blood-brain barrier slows down the progression of PD. Also, it has been shown that activation of poly (ADP-ribose) polymerase (PARP) plays an important role in causing damage to blood-brain barrier. In addition, the PARP inhibitor 3-AB has been shown to protect blood-brain barrier from damage and has neuroprotective effects. In this study, using a lipopolysaccharide (LPS)-induced PD rat model, we investigated whether 3-AB protects blood-brain barrier and dopaminergic neurons from functional damage. LPS significantly increased Evans blue content in the substantia nigra which peaked at 12 h, while administration of 3-AB significantly inhibited the LPS-induced increase in Evans blue content and also significantly increased the expression of the tight junction-associated proteins claudin-5, occludin and ZO-1. 3-AB also increased the number of tyrosine hydroxylase positive cells and reduced the IL-1β and TNF-α content significantly. According to western blot analysis, 3-AB significantly reduced the p-ERK1/2 expression, while the expression of p-p38MAPK increased. These results suggest that 3-AB protects the blood-brain barrier from functional damage in an LPS-induced PD rat model and dopaminergic neurons are protected from degeneration by upregulation of tight junction-associated proteins. These protective effects of 3-AB may be related to modulation of the ERK1/2 pathway.
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, 110001, China.
authors.forename: Xiao-li
authors.initials: XL
authors.lastname: Wu
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Yun-hui
authors.initials: YH
authors.lastname: Liu
authors.forename: Yi-xue
authors.initials: YX
authors.lastname: Xue
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D062507:Claudin-5 / Q000235:genetics / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D062793:Occludin / Q000235:genetics / Q000378:metabolism; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D001549:Benzamides; D062507:Claudin-5; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D062793:Occludin; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; C025160:3-aminobenzamide; D014446:Tyrosine 3-Monooxygenase; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases