Next Article in Journal
BR-BCSC Signature: The Cancer Stem Cell Profile Enriched in Brain Metastases that Predicts a Worse Prognosis in Lymph Node-Positive Breast Cancer
Next Article in Special Issue
Seeding Propensity and Characteristics of Pathogenic αSyn Assemblies in Formalin-Fixed Human Tissue from the Enteric Nervous System, Olfactory Bulb, and Brainstem in Cases Staged for Parkinson’s Disease
Previous Article in Journal
Calcitriol Suppresses HIF-1 and HIF-2 Transcriptional Activity by Reducing HIF-1/2α Protein Levels via a VDR-Independent Mechanism
Previous Article in Special Issue
Is It Meanwhile Biomedical Sciences or Still “Ars Medica”?
Article

Changes in Striatal Medium Spiny Neuron Morphology Resulting from Dopamine Depletion Are Reversible

1
Department of Neurology, RWTH Aachen University, 52074 Aachen, Germany
2
JARA-Institute Molecular Neuroscience and Neuroimaging, Forschungszentrum Jülich GmbH and RWTH Aachen University, 52074 Aachen, Germany
3
Department of Neurology, Technische Universität Dresden, 01307 Dresden, Germany
4
Deutsches Zentrum für Neurodegenerative Erkrankungen, 01307 Dresden, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(11), 2441; https://doi.org/10.3390/cells9112441
Received: 20 October 2020 / Revised: 5 November 2020 / Accepted: 6 November 2020 / Published: 9 November 2020
(This article belongs to the Collection Molecular and Cellular Mechanisms of Parkinson's Disease)
The classical motor symptoms of Parkinson’s disease (PD) are caused by degeneration of dopaminergic neurons in the substantia nigra, which is followed by secondary dendritic pruning and spine loss at striatal medium spiny neurons (MSN). We hypothesize that these morphological changes at MSN underlie at least in part long-term motor complications in PD patients. In order to define the potential benefits and limitations of dopamine substitution, we tested in a mouse model whether dendritic pruning and spine loss can be reversible when dopaminergic axon terminals regenerate. In order to induce degeneration of nigrostriatal dopaminergic neurons we used the toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in C57BL/6J mice; 30 mg/kg MPTP was applied i.p. on five consecutive days. In order to assess the consequences of dopamine depletion, mice were analyzed 21 days after the last injection. In order to test reversibility of MSN changes we exploited the property of this model that striatal axon terminals regenerate by sprouting within 90 days and analyzed a second cohort 90 days after MPTP. Degeneration of dopaminergic neurons was confirmed by counting TH-positive neurons in the substantia nigra and by analyzing striatal catecholamines. Striatal catecholamine recovered 90 days after MPTP. MSN morphology was visualized by Golgi staining and quantified as total dendritic length, number of dendritic branch points, and density of dendritic spines. All morphological parameters of striatal MSN were reduced 21 days after MPTP. Statistical analysis indicated that dendritic pruning and the reduction of spine density represent two distinct responses to dopamine depletion. Ninety days after MPTP, all morphological changes recovered. Our findings demonstrate that morphological changes in striatal MSN resulting from dopamine depletion are reversible. They suggest that under optimal conditions, symptomatic dopaminergic therapy might be able to prevent maladaptive plasticity and long-term motor complications in PD patients.
View Full-Text
Keywords: spiny projection neurons; striatum; spine density; dendrite morphology spiny projection neurons; striatum; spine density; dendrite morphology
Show Figures

Graphical abstract

MDPI and ACS Style

Witzig, V.S.; Komnig, D.; Falkenburger, B.H. Changes in Striatal Medium Spiny Neuron Morphology Resulting from Dopamine Depletion Are Reversible. Cells 2020, 9, 2441. https://doi.org/10.3390/cells9112441

AMA Style

Witzig VS, Komnig D, Falkenburger BH. Changes in Striatal Medium Spiny Neuron Morphology Resulting from Dopamine Depletion Are Reversible. Cells. 2020; 9(11):2441. https://doi.org/10.3390/cells9112441

Chicago/Turabian Style

Witzig, Victoria S., Daniel Komnig, and Björn H. Falkenburger. 2020. "Changes in Striatal Medium Spiny Neuron Morphology Resulting from Dopamine Depletion Are Reversible" Cells 9, no. 11: 2441. https://doi.org/10.3390/cells9112441

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop