The temporal sequence of gut peptide CNS interactions tracked in vivo by magnetic resonance imaging.
Hormonal satiety signals secreted by the gut play a pivotal role in the physiological control of appetite. However, therapeutic exploitation of the gut-brain axis requires greater insight into the interaction of gut hormones with CNS circuits of appetite control. Using the manganese ion (Mn2+) as an activity-dependent magnetic resonance imaging (MRI) contrast agent, we showed an increase in signal intensity (SI) in key appetite-regulatory regions of the hypothalamus, including the arcuate, paraventricular, and ventromedial nuclei, after peripheral injection of the orexigenic peptide ghrelin. Conversely, administration of the anorexigenic hormone peptide YY(3-36) caused a reduction in SI. In both cases, the changes in SI recorded in the hypothalamic arcuate nucleus preceded the effect of these peptides on food intake. Intravenous Mn2+ itself did not significantly alter ghrelin-mediated expression of the immediate early gene product c-Fos, nor did it cause abnormalities of behavior or metabolic parameters. We conclude that manganese-enhanced MRI constitutes a powerful tool for the future investigation of the effects of drugs, hormones, and environmental influences on neuronal activity.
Kuo
Yu-Ting
YT
Molecular Imaging Group, Medical Research Council Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, London W12 0NN, United Kingdom.
Parkinson
James R C
JR
Chaudhri
Owais B
OB
Herlihy
Amy H
AH
So
Po-Wah
PW
Dhillo
Waljit S
WS
Small
Caroline J
CJ
Bloom
Stephen R
SR
Bell
Jimmy D
JD
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000502:physiology; D002490:Central Nervous System / Q000378:metabolism* / Q000502:physiology; D004435:Eating / Q000502:physiology; D005768:Gastrointestinal Hormones / Q000378:metabolism*; D054439:Ghrelin / Q000378:metabolism / Q000502:physiology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000378:metabolism* / Q000502:physiology; D013997:Time Factors
D005768:Gastrointestinal Hormones; D054439:Ghrelin; D009478:Neuropeptide Y