Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...

Details

Autor(en) / Beteiligte
Titel
A Transcriptomic Signature of the Hypothalamic Response to Fasting and BDNF Deficiency in Prader-Willi Syndrome
Ist Teil von
  • Cell reports (Cambridge), 2018-03, Vol.22 (13), p.3401-3408
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2018
Link zum Volltext
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
  • 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. [Display omitted] •Overlap between genes expressed in human PWS hypothalamus and mouse Agrp neurons•Downregulated genes are involved in neuronal development•SNORD116 deletion reduces neural development and survival in cells•Alternative splicing is disturbed in PWS Prader-Willi syndrome (PWS) is a genetic obesity syndrome. Bochukova et al. report gene expression changes in the hypothalamus of people with PWS that support neurodegeneration and neuroinflammation as key processes involved in this condition.

Weiterführende Literatur

Empfehlungen zum selben Thema automatisch vorgeschlagen von bX