Refine
Has Fulltext
- yes (41)
Is part of the Bibliography
- yes (41)
Year of publication
Document Type
- Journal article (39)
- Conference Proceeding (1)
- Doctoral Thesis (1)
Keywords
- bipolar disorder (5)
- BDNF (2)
- STR profile (2)
- biodiversity (2)
- decomposition (2)
- extracellular matrix (2)
- fibrosis (2)
- global change (2)
- hepatic stellate cell (2)
- liver (2)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (17)
- Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie (8)
- Lehrstuhl für Tissue Engineering und Regenerative Medizin (6)
- Rudolf-Virchow-Zentrum (4)
- Institut für Geographie und Geologie (3)
- Pathologisches Institut (3)
- Comprehensive Cancer Center Mainfranken (2)
- Institut für Humangenetik (2)
- Institut für Klinische Epidemiologie und Biometrie (2)
- Institut für Klinische Neurobiologie (2)
Sonstige beteiligte Institutionen
Highlights
• Dopamine receptor-1 activation induces TrkB cell-surface expression in striatal neurons
• Dopaminergic deficits cause TrkB accumulation and clustering in the ER
• TrkB clusters colocalize with cargo receptor SORCS-2 in direct pathway striatal neurons
• Intracellular TrkB clusters fail to fuse with lysosomes after dopamine depletion
Summary
Disturbed motor control is a hallmark of Parkinson’s disease (PD). Cortico-striatal synapses play a central role in motor learning and adaption, and brain-derived neurotrophic factor (BDNF) from cortico-striatal afferents modulates their plasticity via TrkB in striatal medium spiny projection neurons (SPNs). We studied the role of dopamine in modulating the sensitivity of direct pathway SPNs (dSPNs) to BDNF in cultures of fluorescence-activated cell sorting (FACS)-enriched D1-expressing SPNs and 6-hydroxydopamine (6-OHDA)-treated rats. DRD1 activation causes enhanced TrkB translocation to the cell surface and increased sensitivity for BDNF. In contrast, dopamine depletion in cultured dSPN neurons, 6-OHDA-treated rats, and postmortem brain of patients with PD reduces BDNF responsiveness and causes formation of intracellular TrkB clusters. These clusters associate with sortilin related VPS10 domain containing receptor 2 (SORCS-2) in multivesicular-like structures, which apparently protects them from lysosomal degradation. Thus, impaired TrkB processing might contribute to disturbed motor function in PD.