Inactivation of fibroblast growth factor binding protein 3 causes anxiety-related behaviors

Yasunari Yamanaka, Ayumi Kitano, Keizo Takao, Anchalee Prasansuklab, Taisei Mushiroda, Keiko Yamazaki, Tomohiro Kumada, Minoru Shibata, Yuki Takaoka, Tomonari Awaya, Takeo Kato, Takaya Abe, Nakao Iwata, Tsuyoshi Miyakawa, Yusuke Nakamura, Tatsutoshi Nakahata, Toshio Heike

研究成果: Article

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The neurobiological mechanisms of emotional modulation and the molecular pathophysiology of anxiety disorders are largely unknown. The fibroblast growth factor (FGF) family has been implicated in the regulation of many physiological and pathological processes, which include the control of emotional behaviors. The present study examined mice with a targeted deletion of the fgf-bp3 gene, which encodes a novel FGF-binding protein, in animal models relevant to anxiety. To define the behavioral consequences of FGF-BP3 deficiency, we evaluated fgf-bp3-deficient mice using anxiety-related behavioral paradigms that provide a conflict between the desire to explore an unknown area or objects and the aversion to a brightly lit open space. The fgf-bp3-deficient mice exhibited alterations in time spent in the central area of the open-field arena, were less active in the lit areas of a light/dark transition test, and had a prolonged latency to feed during a novelty-induced hypophagia test. These changes were associated with alterations in light-induced orbitofrontal cortex (OFC) activation in an extracellular signal-regulated kinase (ERK) pathway-dependent manner. These results demonstrate that FGF-BP3 is a potent mediator of anxiety-related behaviors in mice and suggest that distinct pathways regulate emotional behaviors. Therefore, FGF-BP3 plays a critical role in the regulation of emotional states and in the development of anxiety disorders and should be investigated as a therapeutic target for anxiety disease in humans.

元の言語English
ページ(範囲)200-212
ページ数13
ジャーナルMolecular and Cellular Neuroscience
46
発行部数1
DOI
出版物ステータスPublished - 01-01-2011

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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    Yamanaka, Y., Kitano, A., Takao, K., Prasansuklab, A., Mushiroda, T., Yamazaki, K., Kumada, T., Shibata, M., Takaoka, Y., Awaya, T., Kato, T., Abe, T., Iwata, N., Miyakawa, T., Nakamura, Y., Nakahata, T., & Heike, T. (2011). Inactivation of fibroblast growth factor binding protein 3 causes anxiety-related behaviors. Molecular and Cellular Neuroscience, 46(1), 200-212. https://doi.org/10.1016/j.mcn.2010.09.003