Titre :

A transcriptomic signature of the hypothalamic response to fasting and bdnf deficiency in prader-willi syndrome

Auteur(s) :

Bochukova, Elena G. [Auteur]
Lawler, Katherine [Auteur]
Croizier, Sophie [Auteur]
Keogh, Julia M. [Auteur]
Patel, Nisha [Auteur]
Strohbehn, Garth [Auteur]
Lo, Kitty K. [Auteur]
Humphrey, Jack [Auteur]
Hokken-Koelega, Anita [Auteur]
Damen, Layla [Auteur]
Donze, Stephany [Auteur]
Bouret, Sebastien [Auteur]
Plagnol, Vincent [Auteur]
Farooqi, I. Sadaf [Auteur]

Titre de la revue :

Cell reports

Nom court de la revue :

Cell Rep

Numéro :

22

Pagination :

3401-3408

Date de publication :

2018-03-27

ISSN :

2211-1247

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Transcriptional analysis of brain tissue from people with molecularly defined causes of obesity may highlight disease mechanisms and therapeutic targets. We performed RNA sequencing of hypothalamus from individuals with ...
Lire la suite >Transcriptional analysis of brain tissue from people with molecularly defined causes of obesity may highlight disease mechanisms and therapeutic targets. We performed RNA sequencing of hypothalamus from individuals with Prader-Willi syndrome (PWS), a genetic obesity syndrome characterized by severe hyperphagia. We found that upregulated genes overlap with the transcriptome of mouse Agrp neurons that signal hunger, while downregulated genes overlap with the expression profile of Pomc neurons activated by feeding. Downregulated genes are expressed mainly in neuronal cells and contribute to neurogenesis, neurotransmitter release, and synaptic plasticity, while upregulated, predominantly microglial genes are involved in inflammatory responses. This transcriptional signature may be mediated by reduced brain-derived neurotrophic factor expression. Additionally, we implicate disruption of alternative splicing as a potential molecular mechanism underlying neuronal dysfunction in PWS. Transcriptomic analysis of the human hypothalamus may identify neural mechanisms involved in energy homeostasis and potential therapeutic targets for weight loss.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

CHU Lille
Inserm
Université de Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Équipe(s) de recherche :

Développement et plasticité du cerveau neuro-endocrine

Date de dépôt :

2021-06-23T11:42:31Z