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Systemic ghrelin treatment induces rapid, transient and asymmetric changes in the metabolic activity of the mouse brain.

INTRODUCTION
Ghrelin regulates a variety of functions by acting in the brain. The targets of ghrelin in the mouse brain have been mainly mapped using immunolabeling against c-Fos, a transcription factor used as a marker of cellular activation, but such analysis has several limitations. Here, we used positron emission tomography in mice to investigate the brain areas responsive to ghrelin.


METHODS
We analyzed in male mice the brain areas responsive to systemically-injected ghrelin using positron emission tomography imaging of 18F-fluoro-2-deoxyglucose (18F-FDG) uptake, an indicator of metabolic rate. Additionally, we studied if systemic administration of fluorescent-ghrelin or native ghrelin display symmetric accessibility or induction of c-Fos, respectively, in the brain of male mice.


RESULTS
Ghrelin increased 18F-FDG uptake in few specific areas of the isocortex, striatum, pallidum, thalamus and midbrain at 0-10-min post-treatment. At the 10-20- and 20-30-min post-treatment, ghrelin induced mixed changes in 18F-FDG uptake in specific areas of isocortex, striatum, pallidum, thalamus and midbrain, as well as in areas of the olfactory areas, hippocampal and retrohippocampal regions, hypothalamus, pons, medulla and even the cerebellum. Ghrelin-induced changes in 18F-FDG uptake were transient and asymmetric. Systemically-administrated fluorescent-ghrelin labeled midline brain areas known to contain fenestrated capillaries and the hypothalamic arcuate nucleus, where a symmetric labeling was observed. Ghrelin treatment also induced a symmetric increased c-Fos labeling in the arcuate nucleus.


DISCUSSION/CONCLUSION
Systemically-injected ghrelin transiently and asymmetrically affects the metabolic activity of the brain of male mice in a wide range of areas, in a food intake independent manner. The neurobiological bases of such asymmetry seem to be independent of the accessibility of ghrelin into the brain.