The proinflammatory cytokine IL-18 has central anorexigenic effects and was proposed to contribute to loss of appetite observed during sickness. Here we tested in the mouse the hypothesis that IL-18 can decrease food intake by acting on neurons of the bed nucleus of the stria terminalis (BST), a component of extended amygdala recently shown to influence feeding via its projections to the lateral hypothalamus (LH). We found that both subunits of the heterodimeric IL-18 receptor are highly expressed in the BST and that local injection of recombinant IL-18 (50 ng/ml) significantly reduced c-fos activation and food intake for at least 6 h. Electrophysiological experiments performed in BST brain slices demonstrated that IL-18 strongly reduces the excitatory input on BST neurons through a presynaptic mechanism. The effects of IL-18 are cell-specific and were observed in Type III but not in Type I/II neurons. Interestingly, IL-18-sensitve Type III neurons were recorded in the juxtacapsular BST, a region that contains BST-LH projecting neurons. Reducing the excitatory input on Type III GABAergic neurons, IL-18 can increase the firing of glutamatergic LH neurons through a disinhibitory mechanism. Imbalance between excitatory and inhibitory activity in the LH can induce changes in food intake. Effects of IL-18 were mediated by the IL-18R because they were absent in neurons from animals null for IL-18Rα (Il18ra-/-), which lack functional IL-18 receptors. In conclusion, our data show that IL-18 may inhibit feeding by inhibiting the activity of BST Type III GABAergic neurons.
|Data di pubblicazione:||2016|
|Titolo:||The proinflammatory cytokine interleukin 18 regulates feeding by acting on the bed nucleus of the stria terminalis|
|Autori:||Francesconi, Walter; Sánchez-Alavez, Manuel; Berton, Fulvia; Alboni, Silvia; Benatti, Cristina; Mori, Simone; Nguyen, William; Zorrilla, Eric; Moroncini, Gianluca; Tascedda, Fabio; Conti, Bruno|
|Digital Object Identifier (DOI):||10.1523/JNEUROSCI.3919-15.2016|
|Appare nelle tipologie:||Articolo su rivista|
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|Francesconi et al., 2016; The Proinflammatory Cytokine Interleukin 18; J Neurosci.pdf||Versione editoriale||Open Access Visualizza/Apri|
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