DRD1 signaling modulates TrkB turnover and BDNF sensitivity in direct pathway striatal medium spiny neurons.

Autor:	Andreska T; Institute of Clinical Neurobiology, University Hospital Wuerzburg, 97078 Wuerzburg, Germany., Lüningschrör P; Institute of Clinical Neurobiology, University Hospital Wuerzburg, 97078 Wuerzburg, Germany., Wolf D; Institute of Clinical Neurobiology, University Hospital Wuerzburg, 97078 Wuerzburg, Germany., McFleder RL; Department of Neurology, University Hospital Wuerzburg, 97080 Wuerzburg, Germany., Ayon-Olivas M; Institute of Clinical Neurobiology, University Hospital Wuerzburg, 97078 Wuerzburg, Germany., Rattka M; Department of Neurology, University Hospital Wuerzburg, 97080 Wuerzburg, Germany., Drechsler C; Department of Microbiology, Biocenter, Julius-Maximilians-University Wuerzburg, 97074 Wuerzburg, Germany., Perschin V; Imaging Core Facility of the Biocenter, Julius-Maximilians-University Wuerzburg, 97074 Wuerzburg, Germany., Blum R; Department of Neurology, University Hospital Wuerzburg, 97080 Wuerzburg, Germany., Aufmkolk S; Department of Biotechnology and Biophysics, Julius-Maximilians-University Wuerzburg, 97074 Wuerzburg, Germany; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA., Granado N; Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain; CIBERNED, Instituto de Salud Carlos III, 28002 Madrid, Spain., Moratalla R; Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain; CIBERNED, Instituto de Salud Carlos III, 28002 Madrid, Spain., Sauer M; Department of Biotechnology and Biophysics, Julius-Maximilians-University Wuerzburg, 97074 Wuerzburg, Germany., Monoranu C; Department for Neuropathology, Julius-Maximilians-University Wuerzburg, 97080 Wuerzburg, Germany., Volkmann J; Department of Neurology, University Hospital Wuerzburg, 97080 Wuerzburg, Germany., Ip CW; Department of Neurology, University Hospital Wuerzburg, 97080 Wuerzburg, Germany., Stigloher C; Imaging Core Facility of the Biocenter, Julius-Maximilians-University Wuerzburg, 97074 Wuerzburg, Germany., Sendtner M; Institute of Clinical Neurobiology, University Hospital Wuerzburg, 97078 Wuerzburg, Germany. Electronic address: sendtner_m@ukw.de.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Jun 27; Vol. 42 (6), pp. 112575. Date of Electronic Publication: 2023 May 29.
DOI:	10.1016/j.celrep.2023.112575
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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