Systemic administration of Neuregulin-1ß(1) protects dopaminergic neurons in a mouse model of Parkinson's disease.

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Abstract

Neuregulin-1 (Nrg1) is genetically linked to schizophrenia, a disease caused by neurodevelopmental imbalance in dopaminergic function. The Nrg1 receptor ErbB4 is abundantly expressed on midbrain dopaminergic neurons. Nrg1 has been shown to penetrate blood-brain barrier, and peripherally administered Nrg1 activates ErbB4 and leads to a persistent hyperdopaminergic state in neonatal mice. These data prompted us to study the effect of peripheral administration of Nrg1 in the context of Parkinson's disease, a neurodegenerative disorder affecting the dopaminergic system in the adult brain. We observed that systemic injections of the extracellular domain of Nrg1ß(1) (Nrg1ß(1) -ECD) increased dopamine levels in the substantia nigra and striatum of adult mice. Nrg1ß(1) -ECD injections also significantly protected the mouse nigrostriatal dopaminergic system morphologically and functionally against 6-hydroxydopamine-induced toxicity in vivo. Moreover, Nrg1ß(1) -ECD also protected human dopaminergic neurons in vitro against 6-hydroxydopamine. In conclusion, we have identified Nrg1ß(1) -ECD as a neurotrophic factor for adult mouse and human midbrain dopaminergic neurons with peripheral administratability, warranting further investigation as therapeutic option for PD patients.

Detaljer

Författare
  • Thomas Carlsson
  • Friederike R Schindler
  • Matthias Höllerhage
  • Candan Depboylu
  • Oscar Arias-Carrión
  • Stefan Schnurrbusch
  • Thomas W Rösler
  • Wojciech Wozny
  • Gerhard P Schwall
  • Karlfried Groebe
  • Wolfgang H Oertel
  • Patrik Brundin
  • André Schrattenholz
  • Günter U Höglinger
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Neurovetenskaper

Nyckelord

Originalspråkengelska
Sidor (från-till)1066-1074
TidskriftJournal of Neurochemistry
Volym117
Utgåva nummer6
StatusPublished - 2011
PublikationskategoriForskning
Peer review utfördJa