An Indirect Action Contributes to C-Fos Induction in Paraventricular Hypothalamic Nucleus by Neuropeptide Y.

Shengjie Fan,Cheng Huang,Eun Ran Kim,Yong Xu,Janani Dakshinamoorthy,Qingchun Tong

doi:10.1038/srep19980

Abstract

Neuropeptide Y (NPY) is a well-established orexigenic peptide and hypothalamic paraventricular nucleus (PVH) is one major brain site that mediates the orexigenic action of NPY. NPY induces abundant expression of C-Fos, an indicator for neuronal activation, in the PVH, which has been used extensively to examine the underlying NPY orexigenic neural pathways. However, PVH C-Fos induction is in discordance with the abundant expression of NPY receptors, a group of inhibitory Gi protein coupled receptors in the PVH, and with the overall role of PVH neurons in feeding inhibition, suggesting a mechanism of indirect action. Here we showed that the ability of NPY on C-Fos induction in the PVH was blunted in conditions of insulin deficiency and fasting, a condition associated with a high level of NPY and a low level of insulin. Moreover, insulin insufficiency blunted C-Fos induction in the PVH by fasting-induced re-feeding, and insulin and NPY induced c-Fos induction in the same group of PVH neurons. Finally, NPY produced normal C-Fos induction in the PVH with disruption of GABA-A receptors. Thus, our results revealed that PVH C-Fos induction by NPY is mediated by an indirect action, which is at least partially mediated by insulin action, but not GABA-A receptors.

Highlights

IntroductionPrevious electrophysiological studies suggest that Neuropeptide Y (NPY) either directly inhibits PVH neurons or reduces GABAergic inputs to these neurons[20,21,22]
Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. *These authors contributed to this work
This study was designed to address the apparent discrepancy between the hyperphagic effect of Neuropeptide Y (NPY) and its effects on C-Fos induction in the PVH

Summary

Introduction

Previous electrophysiological studies suggest that NPY either directly inhibits PVH neurons or reduces GABAergic inputs to these neurons[20,21,22] These observations, taken together, suggest that the C-Fos induction by NPY in the PVH may be mediated through an indirect action. Recent studies suggest that insulin is capable of effectively modulating neuron activity, raising a possibility for insulin action in mediating NPY induction of C-Fos in the PVH. GABA-A receptors in the PVH have been suggested to mediate NPY action on modulating PVH neuron activity and feeding[20,26], raising a possibility for PVH GABA-A receptors in mediating NPY induction of C-Fos. in the current study, we examined whether insulin action and PVH GABA-A receptors contribute to NPY induced C-Fos in the PVH

Methods

Results

Conclusion