Neuropeptide Y: Role in Emotion and Alcohol Dependence

Carvajal, Cristina; Dumont, Yvan; Quirion, Rémi

doi:10.2174/187152706776359592

Cited by 41 publications

(4 citation statements)

References 175 publications

(267 reference statements)

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“…To date, studies have implicated Npy in the regulation of emotion, anxiety, consummatory behavior as well as alcohol dependence [41]. An inverse relationship has been documented between Npy levels (mRNA, protein) and alcohol-seeking behavior.…”

Section: Corroborative Evidence and Candidate Gene Validationmentioning

confidence: 99%

From QTL to Candidate Gene: A Genetic Approach to Alcoholism Research

Spence¹,

Liang²,

Liu³

et al. 2009

CDAR

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A major focus of research in alcohol-related disorders is to identify the genes and pathways that modulate alcohol-seeking behavior. In light of this, animal models have been established to study various aspects of alcohol dependence. The selectively bred alcohol-preferring (P) and -nonpreferring (NP) lines were developed from Wistar rats to model high and low voluntary alcohol consumption, respectively. Using inbred P and NP strains, a strong QTL (LOD-9.2) for alcohol consumption was identified on rat chromosome 4. To search for candidate genes that underlie this chromosomal region, complementary molecular-based strategies were implemented to identify genetic targets that likely contribute to the linkage signal. In an attempt to validate these genetic targets, corroborative studies have been utilized including pharmacological studies, knock-out/transgenic models as well as human association studies. Thus far, three candidate genes, neuropeptide Y (Npy), α-synuclein (Snca), and corticotrophin-releasing factor receptor 2 (Crhr2), have been identified that may account for the linkage signal. With the recent advancements in bioinformatics and molecular biology, QTL analysis combined with molecular-based strategies provides a systematic approach to identify candidate genes that contribute to various aspects of addictive behavior.

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Section: Corroborative Evidence and Candidate Gene Validationmentioning

confidence: 99%

From QTL to Candidate Gene: A Genetic Approach to Alcoholism Research

Spence¹,

Liang²,

Liu³

et al. 2009

CDAR

View full text Add to dashboard Cite

show abstract

“…Consequently, its potential as target for modulating food consumption and thus, obesity, is intensely investigated [1]. Besides this capacity, the NPY system also has multiple other functions, for instance in the control of mood and anxiety or ethanol intake [2, 3]. The hallmark features of NPY and the related peptides PYY and PP are a C-terminal arginine-phenylalanine/tyrosine sequence and an amidated carboxy-terminus (RxRF/Yamide), which are essential for activation of their four cognate G protein-coupled receptors (GPCRs) in most mammals [4].…”

Section: Introductionmentioning

confidence: 99%

Pharmacological and functional similarities of the human neuropeptide Y system in C. elegans challenges phylogenetic views on the FLP/NPR system

et al. 2019

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Background The neuropeptide Y system affects various processes, among others food intake, and is frequently discussed in the context of targeting obesity. Studies in model organisms are indispensable to enable molecular studies in a physiological context. Although the NPY system is evolutionarily conserved in all bilaterians, in the widely used model Caenorhabditis elegans there is controversy on the existence of NPY orthologous molecules. While the FMRFamide-like peptide (FLP)/Neuropeptide receptor-Resemblance (NPR) system in the nematode was initially suggested to be orthologous to the mammalian NPY system, later global phylogenetic studies indicate that FLP/NPR is protostome-specific. Methods We performed a comprehensive pharmacological study of the FLP/NPR system in transfected cells in vitro, and tested for functional substitution in C. elegans knockout strains. Further, we phenotypically compared different flp loss-of-function strains. Differences between groups were compared by ANOVA and post-hoc testing (Dunnett, Bonferroni). Results Our pharmacological analysis of the FLP/NPR system including formerly functionally uncharacterized NPY-like peptides from C. elegans demonstrates that G protein-coupling and ligand requirements for receptor activation are similar to the human NPY system. In vitro and in vivo analyses show cross-reactivity of NPY with the FLP/NPR system manifesting in the ability of the human GPCRs to functionally substitute FLP/NPR signaling in vivo. The high pharmacological/functional similarities enabled us to identify C. elegans FLP-14 as a key molecule in avoidance behavior. Conclusions Our data demonstrate the pharmacological and functional similarities of human NPY and C. elegans NPR systems. This adds a novel perspective to current phylogenetic reconstructions of the neuropeptide Y system. NPY and NPR receptors are pharmacologically so similar that the human receptors can functionally compensate for the C. elegans ones, suggesting orthologous relationships. This is also underlined by the presence of NPY-like peptides and parallels in peptide requirements for receptor activation. Further, the results presented here highlight the potential of this knowledge for physiological as well as molecular studies on neuropeptide GPCRs such as the NPY system in the future.

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“…Within this list, the NPY gene is a pleiotropic central nervous system gene, particularly interesting for its potential therapeutic perspectives. Despite not being associated with ASD so far, it is involved in the regulation of emotional as well as anxiety-related behaviors and has been associated with depression [ 50 ]. In mice models, activation of neuropeptide Y neurons has been linked to the presence of stereotypic ASD-like behaviors [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Epigenetics of Autism Spectrum Disorders: A Multi-level Analysis Combining Epi-signature, Age Acceleration, Epigenetic Drift and Rare Epivariations Using Public Datasets

Davide,

Rebecca,

Irene

et al. 2023

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Background: Epigenetics of Autism Spectrum Disorders (ASD) is still an understudied field. The majority of the studies on the topic used an approach based on mere classification of cases and controls. Objective: The present study aimed at providing a multi-level approach in which different types of ep- igenetic analysis (epigenetic drift, age acceleration) are combined. Methods: We used publicly available datasets from blood (n = 3) and brain tissues (n = 3), separately. Firstly, we evaluated for each dataset and meta-analyzed the differential methylation profile between cas- es and controls. Secondly, we analyzed age acceleration, epigenetic drift and rare epigenetic variations. Results: We observed a significant epi-signature of ASD in blood but not in brain specimens. We did not observe significant age acceleration in ASD, while epigenetic drift was significantly higher com- pared to controls. We reported the presence of significant rare epigenetic variations in 41 genes, 35 of which were never associated with ASD. Almost all genes were involved in pathways linked to ASD etiopathogenesis (i.e., neuronal development, mitochondrial metabolism, lipid biosynthesis and anti- gen presentation). Conclusion: Our data support the hypothesis of the use of blood epi-signature as a potential tool for diagnosis and prognosis of ASD. The presence of an enhanced epigenetic drift, especially in brain, which is linked to cellular replication, may suggest that alteration in epigenetics may occur at a very early developmental stage (i.e., fetal) when neuronal replication is still high.

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Neuropeptide Y: Role in Emotion and Alcohol Dependence

Cited by 41 publications

References 175 publications

From QTL to Candidate Gene: A Genetic Approach to Alcoholism Research

From QTL to Candidate Gene: A Genetic Approach to Alcoholism Research

Pharmacological and functional similarities of the human neuropeptide Y system in C. elegans challenges phylogenetic views on the FLP/NPR system

Epigenetics of Autism Spectrum Disorders: A Multi-level Analysis Combining Epi-signature, Age Acceleration, Epigenetic Drift and Rare Epivariations Using Public Datasets

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