title: Viral-mediated delivery of an RXFP3 agonist into brain promotes arousal in mice.
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(power)8 genomic copies in 2 microl) 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.
authors.forename: Craig M
authors.initials: CM
authors.lastname: Smith
authors.forename: Anna
authors.initials: A
authors.lastname: Blasiak
authors.forename: Despina E
authors.initials: DE
authors.lastname: Ganella
authors.forename: Berenice E
authors.initials: BE
authors.lastname: Chua
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Layfield
authors.forename: Ross A D
authors.initials: RA
authors.lastname: Bathgate
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Gundlach
mesh_terms: D000818:Animals; D001143:Arousal / Q000235:genetics*; D001921:Brain / Q000502:physiology*; D005822:Genetic Vectors; D016086:Lentivirus / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000235:genetics*; D012065:Relaxin / Q000235:genetics*
chemical_list: D043562:Receptors, G-Protein-Coupled; C505050:SALPR protein, mouse; C512898:relaxin-3 protein, mouse; D012065:Relaxin