Frontiers in Molecular Neuroscience (Apr 2017)

Adropin Is a Key Mediator of Hypoxia Induced Anti-Dipsogenic Effects via TRPV4-CamKK-AMPK Signaling in the Circumventricular Organs of Rats

  • Qing-Yuan Huang,
  • Qing-Yuan Huang,
  • Qing-Yuan Huang,
  • Fan Yang,
  • Fan Yang,
  • Fan Yang,
  • Li Zhou,
  • Xu Qian,
  • Dong Wang,
  • Dong Wang,
  • Dong Wang,
  • Wen-Juan He,
  • Wen-Juan He,
  • Wen-Juan He,
  • Zhong-wei Tang,
  • Zhong-wei Tang,
  • Zhong-wei Tang,
  • Jun Yin,
  • Jun Yin,
  • Jun Yin

DOI
https://doi.org/10.3389/fnmol.2017.00105
Journal volume & issue
Vol. 10

Abstract

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Water intake reduction (anti-dipsogenic effects) under hypoxia has been well established, but the underlying reason remains unknown. Our previous report indicated that activated TRPV4 neurons in SFO are associated with anti-dipsogenic effects under hypoxia. Although low partial pressure of blood oxygen directly activates TRPV4, humoral factors could also be involved. In the present study, we hypothesize that adropin, a new endogenous peptide hormone, was rapidly increased (serum and brain) concomitant with reduced water intake in early hypoxia. Also, the nuclear expression of c-Fos, a marker for neuronal activation, related to water-consumption (SFO and MnPO) was inhibited. These effects were mitigated by a scavenger, rat adropin neutralizing antibody, which effectively neutralized adropin under hypoxia. Interestingly, injection of recombinant adropin in the third ventricle of the rats also triggered anti-dipsogenic effects and reduced c-Fos positive cells in SFO, but these effects were absent when TRPV4 was knocked down by shRNA. Moreover, adropin-activated CamKK-AMPK signaling related to TRPV4 calcium channel in SFO in normoxia. These results revealed that dissociative adropin was elevated in acute hypoxia, which was responsible for anti-dipsogenic effects by altering TRPV4-CamKK-AMPK signaling in SFO.

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