Systemic administration of neuregulin-1 beta(1) protects dopaminergic neurons in a mouse model of Parkinson's disease

作者：Carlsson Thomas; Schindler Friederike R; Hoellerhage Matthias; Depboylu Candan; Arias Carrion Oscar; Schnurrbusch Stefan; Roesler Thomas W; Wozny Wojciech; Schwall Gerhard P; Groebe Karlfried; Oertel Wolfgang H; Brundin Patrik; Schrattenholz Andre; Hoeglinger Guenter U

来源：Journal of Neurochemistry, 2011, 117(6): 1066-1074.

DOI：10.1111/j.1471-4159.2011.07284.x

• dopamine
• ErbB4 receptor
• neuregulin
• neuroprotection
• Parkinson's disease

P>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 Nrg1 beta(1) (Nrg1 beta(1)-ECD) increased dopamine levels in the substantia nigra and striatum of adult mice. Nrg1 beta(1)-ECD injections also significantly protected the mouse nigrostriatal dopaminergic system morphologically and functionally against 6-hydroxydopamine-induced toxicity in vivo. Moreover, Nrg1 beta(1)-ECD also protected human dopaminergic neurons in vitro against 6-hydroxydopamine. In conclusion, we have identified Nrg1 beta(1)-ECD as a neurotrophic factor for adult mouse and human midbrain dopaminergic neurons with peripheral administratability, warranting further investigation as therapeutic option for Parkinson's disease patients.

• 出版日期2011-6