Article (Scientific journals)
PKG1alpha oxidation negatively regulates food seeking behaviour and reward.
Duraffourd, Celine; Huckstepp, Robert T. R.; Braren, Ingke et al.
2018In Redox Biology, 21, p. 101077
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Keywords :
Food-seeking behaviour; PKG1alpha; Reward; Ventral Tegmental Area
Abstract :
[en] Genes that are highly conserved in food seeking behaviour, such as protein kinase G (PKG), are of interest because of their potential role in the global obesity epidemic. PKG1alpha can be activated by binding of cyclic guanosine monophosphate (cGMP) or oxidant-induced interprotein disulfide bond formation between the two subunits of this homodimeric kinase. PKG1alpha activation by cGMP plays a role in reward and addiction through its actions in the ventral tegmental area (VTA) of the brain. 'Redox dead' C42S PKG1alpha knock-in (KI) mice, which are fully deficient in oxidant-induced disulfide-PKG1alpha formation, display increased food seeking and reward behaviour compared to wild-type (WT) littermates. Rewarding monoamines such as dopamine, which are released during feeding, are metabolised by monoamine oxidase to generate hydrogen peroxide that was shown to mediate PKG1alpha oxidation. Indeed, inhibition of monoamine oxidase, which prevents it producing hydrogen peroxide, attenuated PKG1alpha oxidation and increased sucrose preference in WT, but not KI mice. The deficient reward phenotype of the KI mice was rescued by expressing WT kinase that can form the disulfide state in the VTA using an adeno-associated virus, consistent with PKG1alpha oxidation providing a break on feeding behaviour. In conclusion, disulfide-PKG1alpha in VTA neurons acts as a negative regulator of feeding and therefore may provide a novel therapeutic target for obesity.
Disciplines :
Neurosciences & behavior
Author, co-author :
Duraffourd, Celine
Huckstepp, Robert T. R.
Braren, Ingke
Fernandes, Cathy
Brock, Olivier ;  Université de Liège - ULiège
Delogu, Alessio
Prysyazhna, Oleksandra
Burgoyne, Joseph
Eaton, Philip
Language :
English
Title :
PKG1alpha oxidation negatively regulates food seeking behaviour and reward.
Publication date :
2018
Journal title :
Redox Biology
eISSN :
2213-2317
Publisher :
Elsevier, Netherlands
Volume :
21
Pages :
101077
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2018. Published by Elsevier B.V.
Available on ORBi :
since 17 January 2019

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