NDLI: Acute selective ablation of rat insulin promoter-expressing (RIPHER) neurons defines their orexigenic nature

Content Provider	PubMed Central
Author	Rother, Eva Belgardt, Bengt F. Eva, Tsaousidou Hampel, Brigitte Waisman, Ari Myers, Martin G. Brüning, Jens C.
Abstract	Rat insulin promoter (RIP)-expressing neurons in the hypothalamus control body weight and energy homeostasis. However, genetic approaches to study the role of these neurons have been limited by the fact that RIP expression is predominantly found in pancreatic β-cells, which impedes selective targeting of neurons. To define the function of hypothalamic RIP-expressing neurons, we set out to acutely and selectively eliminate them via diphtheria toxin-mediated ablation. Therefore, the diphtheria toxin receptor transgene was specifically expressed upon RIP-specific Cre recombination using a RIP-Cre line first described by Herrera (RIPHER-Cre) [Herrera PL (2000) Development 127:2317–2322]. Using proopiomelanocortin–expressing cells located in the arcuate nucleus of the hypothalamus and in the pituitary gland as a model, we established a unique protocol of intracerebroventricular application of diphtheria toxin to efficiently ablate hypothalamic cells with no concomitant effect on pituitary proopiomelanocortin–expressing corticotrophs in the mouse. Using this approach to ablate RIPHER neurons in the brain, but not in the pancreas, resulted in decreased food intake and loss of body weight and fat mass. In addition, ablation of RIPHER neurons caused increased c-Fos immunoreactivity of neurons in the paraventricular nucleus (PVN) of the hypothalamus. Moreover, transsynaptic tracing of RIPHER neurons revealed labeling of neurons located in the PVN and dorsomedial hypothalamic nucleus. Thus, our experiments indicate that RIPHER neurons inhibit anorexigenic neurons in the PVN, revealing a basic orexigenic nature of these cells.
Related Links	http://dx.doi.org/10.1073/pnas.1206147109
Ending Page	18137
Page Count	6
Starting Page	18132
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	44
Volume Number	109
Language	English
Publisher	National Academy of Sciences
Publisher Date	2012-10-30
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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