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SorCS2 Regulates Dopaminergic Wiring and BDNF-Dependent Plasticity, Anders Nykjaer, MD/PhD
October 5, 2016 @ 1:50 pm - 2:15 pm
Anders Nykjaer, MD/PhD, Professor of Medical Biochemistry; Director of the Lundbeck Foundation Research Centre MIND; Danish Research Institute of Translational Neuroscience – DANDRITE; Nordic – EMBL Partnership of Molecular Medicine; Aarhus University, Denmark —
It is well accepted that psychiatric disorders commonly result from developmental deficits superimposed acute changes in synaptic plasticity. Multiple studies have reported association between SORCS2 and ADHD, schizophrenia and bipolar disorder but the underlying molecular mechanism has remained elusive. We find that the receptor SorCS2 exhibits highly distinct functions in the developing and adult brain. During formation of the dopaminergic system SorCS2 binds proBDNF to induce growth cone collapse in dopaminergic processes, whereas in postmitotic neurons it is required for proBDNF and BDNF to regulate NMDA receptor-dependent synaptic strength. Accordingly, mice devoid in SorCS2 expression display severe behavioral abnormalities compatible with ADHD and schizophrenia. Our data provide a mechanistic link between polymorphisms in SORCS2 and mental disorders