Journal
JOURNAL OF MOLECULAR NEUROSCIENCE
Volume 53, Issue 1, Pages 1-9Publisher
HUMANA PRESS INC
DOI: 10.1007/s12031-013-0175-5
Keywords
Blood-brain barrier; Neuron; 3-AB; Tight junction-associated protein; Protection; Parkinson's disease
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Funding
- Natural Science Foundation of China [81171131, 81172197, 81072056, 81272564, 81272795]
- special fund for Scientific Research of Doctor-degree Subjects in Colleges and Universities [20102104110009]
- Natural Science Foundation of Liaoning Province in China [201102300]
- Liaoning Science and Technology Plan Projects [2011225020]
- Shenyang Science and Technology Plan Projects [F13-220-9-15, F13-316-1-16, F13-316-1-19]
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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-alpha and IL-1 beta 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-1 beta and TNF-alpha 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.
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