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Effects of Poly (ADP-ribose) Polymerase Inhibitor 3-Aminobenzamide on Blood–Brain Barrier and Dopaminergic Neurons of Rats with Lipopolysaccharide-Induced Parkinson’s Disease

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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.

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Acknowledgments

This work is supported by grants from the Natural Science Foundation of China (81171131, 81172197, 81072056, 81272564, 81272795), the special fund for Scientific Research of Doctor-degree Subjects in Colleges and Universities (20102104110009), the Natural Science Foundation of Liaoning Province in China (no. 201102300), Liaoning Science and Technology Plan Projects (no. 2011225020), and Shenyang Science and Technology Plan Projects (nos. F13-220-9-15, F13-316-1-16, and F13-316-1-19).

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Authors and Affiliations

  1. Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, 110001, China

    Xiao-li Wu, Ping Wang & Yi-xue Xue

  2. Institute of Pathology and Pathophysiology, China Medical University, Shenyang, 110001, China

    Xiao-li Wu, Ping Wang & Yi-xue Xue

  3. Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, 110004, China

    Xiao-li Wu

  4. Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China

    Yun-hui Liu

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  1. Xiao-li Wu
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  2. Ping Wang
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Correspondence to Yi-xue Xue.

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Fig. S1

The effects of different PJ34 concentrations on BBB permeability at 12 h after LPS injection were detected by extravasation of EB. EB content is given as means ± SD (n = 5, each). *P < 0.05 versus 0 mg/kg group; # P < 0.05 versus 5 mg/kg group (JPEG 8 kb)

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Wu, Xl., Wang, P., Liu, Yh. et al. Effects of Poly (ADP-ribose) Polymerase Inhibitor 3-Aminobenzamide on Blood–Brain Barrier and Dopaminergic Neurons of Rats with Lipopolysaccharide-Induced Parkinson’s Disease. J Mol Neurosci 53, 1–9 (2014). https://doi.org/10.1007/s12031-013-0175-5

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  • DOI: https://doi.org/10.1007/s12031-013-0175-5

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