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Axonal protection by brain-derived neurotrophic factor associated with CREB phosphorylation in tumor necrosis factor-α-induced optic nerve degeneration

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Abstract

Brain-derived neurotrophic factor (BDNF) is a potent survival and developmental factor that is regulated by cyclic AMP-response element binding protein (CREB) and has a protective effect against retinal ganglion cell (RGC) death. However, the effect of BDNF on the optic nerve axonal degeneration remains to be examined. In this study, we show that intravitreal injection of tumor necrosis factor (TNF)-α induces transient increases in phosphorylated-CREB (p-CREB) and BDNF expression in the optic nerve. Administration of exogenous BDNF further increased the p-CREB and endogenous BDNF level and exerted a neuroprotective effect against TNF-α-induced axonal loss. The increases in BDNF mRNA and protein induced by TNF-α were inhibited significantly by a CRE decoy oligonucleotide. The protective effect of exogenous BDNF on axons was also inhibited by the CRE decoy oligonucleotide. These results suggest that the protective effect of exogenous BDNF may be associated with increases in CREB phosphorylation and endogenous BDNF in the optic nerve.

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Acknowledgments

This work was supported by Grant-in-Aid No. 18791303 (Y.K.), No. 20791285 (Y.K.) and No. 19592045 (S.U.) from the Ministry of Education, Culture, Sports, Science, and Technology of the Japanese Government; and by the Uehara Memorial Foundation (Y.K.).

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Authors and Affiliations

  1. Department of Ophthalmology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan

    Hiromi Fujino, Yasushi Kitaoka, Yasuhiro Hayashi, Yasunari Munemasa, Hiroyuki Takeda & Satoki Ueno

  2. Department of Pharmacology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan

    Toshio Kumai & Shinichi Kobayashi

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  1. Hiromi Fujino
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  2. Yasushi Kitaoka
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  3. Yasuhiro Hayashi
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  4. Yasunari Munemasa
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  5. Hiroyuki Takeda
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Correspondence to Yasushi Kitaoka.

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Fujino, H., Kitaoka, Y., Hayashi, Y. et al. Axonal protection by brain-derived neurotrophic factor associated with CREB phosphorylation in tumor necrosis factor-α-induced optic nerve degeneration. Acta Neuropathol 117, 75–84 (2009). https://doi.org/10.1007/s00401-008-0440-9

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  • DOI: https://doi.org/10.1007/s00401-008-0440-9

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