Inactivation of fibroblast growth factor binding protein 3 causes anxiety-related behaviors.
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.
Yamanaka
Yasunari
Y
Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Kitano
Ayumi
A
Takao
Keizo
K
Prasansuklab
Anchalee
A
Mushiroda
Taisei
T
Yamazaki
Keiko
K
Kumada
Tomohiro
T
Shibata
Minoru
M
Takaoka
Yuki
Y
Awaya
Tomonari
T
Kato
Takeo
T
Abe
Takaya
T
Iwata
Nakao
N
Miyakawa
Tsuyoshi
T
Nakamura
Yusuke
Y
Nakahata
Tatsutoshi
T
Heike
Toshio
T
D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000378:metabolism*; D001522:Behavior, Animal / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009483:Neuropsychological Tests
D002352:Carrier Proteins; C489453:Fgfbp1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; C559129:fibroblast growth factor binding protein 3, mouse; D016222:Fibroblast Growth Factor 2; D048049:Extracellular Signal-Regulated MAP Kinases