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DAPT protects brain against cerebral ischemia by down-regulating the expression of Notch 1 and Nuclear factor kappa B in rats

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Abstract

Gamma-secretase inhibitor, N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester (DAPT) suppresses the activation of Notch 1 signaling, which is recognized as the cell fate signaling and may participate in inflammatory processes together with NF-κB pathway that contributes to the brain damage after stroke. DAPT has important pharmacological roles in many diseases. However, little is known about the effect of DAPT on NF-κB during cerebral ischemia. This study investigated the time course expression of Notch 1 and the effects of DAPT on Notch 1 and NF-κB after MCAO. The results showed that Notch 1 signaling was up-regulated at the early stage after MCAO, DAPT down-regulated the expression of Notch 1 and NF-κB and protected brain from damage caused by MCAO. These results may indicate that the downregulation of Notch 1–NF-κB pathway after ischemia by administration of DAPT is a potential mechanism for its protection.

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Acknowledgments

This work was funded by Hebei Province, No: C2010000564 and No: 10276104D and a Grant from the Major State Basic Research Development Program of China (No. 2009CB521905).

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Authors and Affiliations

  1. Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No. 6 Tiantanxili, Dongcheng District, Beijing, 100050, China

    Shuya Li & Yongjun Wang

  2. Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, China

    Xiangjian Zhang, Hui Ji, Yuanyuan Du & Haichao Liu

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  1. Shuya Li
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Correspondence to Yongjun Wang.

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Li, S., Zhang, X., Wang, Y. et al. DAPT protects brain against cerebral ischemia by down-regulating the expression of Notch 1 and Nuclear factor kappa B in rats. Neurol Sci 33, 1257–1264 (2012). https://doi.org/10.1007/s10072-012-0948-6

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  • DOI: https://doi.org/10.1007/s10072-012-0948-6

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