Vol 118, No 1 (Supplement) 2013
Original Article

Viral-mediated delivery of an RXFP3 agonist into brain promotes arousal in mice

PDF
  • Craig M. Smith,
  • Anna Blasiak,
  • Despina E. Ganella,
  • Berenice E. Chua,
  • Sharon L. Layfield,
  • Ross A.D. Bathgate,
  • Andrew L. Gundlach

Published 2014-01-11

Keywords

  • Relaxin-3,
  • RXFP3,
  • R3/I5,
  • lentivirus,
  • arousal

How to Cite

Smith, C. M., Blasiak, A., Ganella, D. E., Chua, B. E., Layfield, S. L., Bathgate, R. A., & Gundlach, A. L. (2014). Viral-mediated delivery of an RXFP3 agonist into brain promotes arousal in mice. Italian Journal of Anatomy and Embryology, 118(1), 42–46. Retrieved from https://oajournals.fupress.net/index.php/ijae/article/view/3241
Copyright Notice

Abstract

Anatomical and functional studies of central relaxin-3/RXFP3 systems suggest they constitute an ascending arousal network. For example, relaxin-3 knockout mice display circadian hypoactivity compared to wild type littermate controls. In studies to explore the effect of chronic RXFP3 activation on behaviour, we engineered a lentiviral construct to constitutively secrete the RXFP3 agonist, R3/I5, and express a green fluorescent protein (GFP) marker in transduced cells. Intracerebroventricular injection of the lenti-R3/I5-GFP virus (~10^8 genomic copies in 2 μl) in adult C57BL/6J mice resulted in GFP expression within cells of the ventricle walls and choroid plexus over a period of 1-4 weeks, suggesting likely chronic R3/I5 secretion and RXFP3 activation in brain regions proximal to the ventricular system. Subsequent testing in automated locomotor cells on day 8 and 9 post-injection revealed that lenti-R3/I5-GFP treated mice displayed prolonged, elevated locomotor activity (~18% higher over the last 15 min on day 8, and over the entire 30 min test on day 9) compared to mice injected with a control lenti-GFP virus, which habituated normally to the novel environment (n=18/12 respectively, p<0.05). These findings are consistent with an earlier report of increased activity scores in rats acutely injected centrally with R3/I5, and further suggest a role for relaxin-3/RXFP3 signalling in promoting behavioural arousal.

PDF