Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Functional hypoxia drives neuroplasticity and neurogenesis via brain erythropoietin

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. An atlas of O-linked glycosylation on peptide hormones reveals diverse biological roles

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Whole genome landscapes of uveal melanoma show an ultraviolet radiation signature in iris tumours

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Author Correction: Mutational and putative neoantigen load predict clinical benefit of adoptive T cell therapy in melanoma

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. S100B and brain derived neurotrophic factor in monozygotic twins with, at risk of and without affective disorders

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Erythropoietin as candidate for supportive treatment of severe COVID-19

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  3. Erythropoietin in Preterm Infants

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Debia Wakhloo
  • Franziska Scharkowski
  • Yasmina Curto
  • Umer Javed Butt
  • Vikas Bansal
  • Agnes A Steixner-Kumar
  • Liane Wüstefeld
  • Ashish Rajput
  • Sahab Arinrad
  • Matthias R Zillmann
  • Anna Seelbach
  • Imam Hassouna
  • Katharina Schneider
  • Abdul Qadir Ibrahim
  • Hauke B Werner
  • Henrik Martens
  • Kamilla Miskowiak
  • Sonja M Wojcik
  • Stefan Bonn
  • Juan Nacher
  • Klaus-Armin Nave
  • Hannelore Ehrenreich
Vis graf over relationer

Erythropoietin (EPO), named after its role in hematopoiesis, is also expressed in mammalian brain. In clinical settings, recombinant EPO treatment has revealed a remarkable improvement of cognition, but underlying mechanisms have remained obscure. Here, we show with a novel line of reporter mice that cognitive challenge induces local/endogenous hypoxia in hippocampal pyramidal neurons, hence enhancing expression of EPO and EPO receptor (EPOR). High-dose EPO administration, amplifying auto/paracrine EPO/EPOR signaling, prompts the emergence of new CA1 neurons and enhanced dendritic spine densities. Single-cell sequencing reveals rapid increase in newly differentiating neurons. Importantly, improved performance on complex running wheels after EPO is imitated by exposure to mild exogenous/inspiratory hypoxia. All these effects depend on neuronal expression of the Epor gene. This suggests a model of neuroplasticity in form of a fundamental regulatory circle, in which neuronal networks-challenged by cognitive tasks-drift into transient hypoxia, thereby triggering neuronal EPO/EPOR expression.

OriginalsprogEngelsk
TidsskriftNature Communications
Vol/bind11
Udgave nummer1
Sider (fra-til)1313
ISSN2041-1723
DOI
StatusUdgivet - 9 mar. 2020

ID: 59921826