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The Journal of Neuroscience, November 7, 2007, 27(45):12341-12348; doi:10.1523/JNEUROSCI.2391-07.2007

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Cellular/Molecular
The Temporal Sequence of Gut Peptide–CNS Interactions Tracked In Vivo by Magnetic Resonance Imaging

Yu-Ting Kuo,^1,4 * James R. C. Parkinson,^3 * Owais B. Chaudhri,^3 * Amy H. Herlihy,² Po-Wah So,² Waljit S. Dhillo,³ Caroline J. Small,³ Stephen R. Bloom,³ and Jimmy D. Bell¹

¹Molecular Imaging Group and ²Biological Imaging Centre, Medical Research Council Clinical Sciences Centre, and ³Department of Metabolic Medicine, Imperial College London, Hammersmith Hospital, London W12 0NN, United Kingdom, and ⁴Department of Medical Imaging, Faculty of Medicine, School of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan

Correspondence should be addressed to Prof. Jimmy D. Bell, Molecular Imaging Group, Medical Research Council Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. Email: jimmy.bell{at}csc.mrc.ac.uk

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.

Key words: hypothalamus; manganese; MRI; appetite; ghrelin; PYY_3–36

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Received Oct. 6, 2006; revised Aug. 1, 2007; accepted Aug. 7, 2007.

Correspondence should be addressed to Prof. Jimmy D. Bell, Molecular Imaging Group, Medical Research Council Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. Email: jimmy.bell{at}csc.mrc.ac.uk

This article has been cited by other articles:

				A. C. Silva and N. A. Bock Manganese-Enhanced MRI: An Exceptional Tool in Translational Neuroimaging Schizophr Bull, July 1, 2008; 34(4): 595 - 604. [Abstract] [Full Text] [PDF]

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