Non-Apoptotic Caspase-3 Activation Mediates Early Synaptic Dysfunction of Indirect Pathway Neurons in the Parkinsonian Striatum

Fieblinger, Tim; Li, Chang; Espa, Elena; Cenci, M. Angela

doi:10.3390/ijms23105470

Submit to this Journal Review for this Journal Edit a Special Issue

Article Menu

...

Open AccessArticle

Non-Apoptotic Caspase-3 Activation Mediates Early Synaptic Dysfunction of Indirect Pathway Neurons in the Parkinsonian Striatum

^1,2,*

¹,

¹ and

^1,*

Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, 223 62 Lund, Sweden

University Medical Center Hamburg-Eppendorf, Institute for Synaptic Physiology, 20251 Hamburg, Germany

Authors to whom correspondence should be addressed.

Academic Editors: Marcello Ciaccio and Alberto Pérez-Mediavilla

Int. J. Mol. Sci. 2022, 23(10), 5470; https://doi.org/10.3390/ijms23105470 (registering DOI)

Received: 22 March 2022 / Revised: 9 May 2022 / Accepted: 12 May 2022 / Published: 13 May 2022

(This article belongs to the Special Issue Neurodegenerative Diseases: From Molecular Basis to Therapy)

View Full-Text Download PDF

Browse Figures

Review Reports Citation Export

Abstract

Non-apoptotic caspase-3 activation is critically involved in dendritic spine loss and synaptic dysfunction in Alzheimer’s disease. It is, however, not known whether caspase-3 plays similar roles in other pathologies. Using a mouse model of clinically manifest Parkinson’s disease, we provide the first evidence that caspase-3 is transiently activated in the striatum shortly after the degeneration of nigrostriatal dopaminergic projections. This caspase-3 activation concurs with a rapid loss of dendritic spines and deficits in synaptic long-term depression (LTD) in striatal projection neurons forming the indirect pathway. Interestingly, systemic treatment with a caspase inhibitor prevents both the spine pruning and the deficit of indirect pathway LTD without interfering with the ongoing dopaminergic degeneration. Taken together, our data identify transient and non-apoptotic caspase activation as a critical event in the early plastic changes of indirect pathway neurons following dopamine denervation. View Full-Text

Keywords: Parkinson’s disease; striatum; caspase-3; spiny projection neurons; dendritic spines; long-term depression; Q-VD-OPh; mice

▼ Show Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Supplementary Material

Supplementary File 1:
ZIP-Document (ZIP, 186 KiB)

Share and Cite

MDPI and ACS Style

Fieblinger, T.; Li, C.; Espa, E.; Cenci, M.A. Non-Apoptotic Caspase-3 Activation Mediates Early Synaptic Dysfunction of Indirect Pathway Neurons in the Parkinsonian Striatum. Int. J. Mol. Sci. 2022, 23, 5470. https://doi.org/10.3390/ijms23105470

AMA Style

Fieblinger T, Li C, Espa E, Cenci MA. Non-Apoptotic Caspase-3 Activation Mediates Early Synaptic Dysfunction of Indirect Pathway Neurons in the Parkinsonian Striatum. International Journal of Molecular Sciences. 2022; 23(10):5470. https://doi.org/10.3390/ijms23105470

Chicago/Turabian Style

Fieblinger, Tim, Chang Li, Elena Espa, and M. A. Cenci. 2022. "Non-Apoptotic Caspase-3 Activation Mediates Early Synaptic Dysfunction of Indirect Pathway Neurons in the Parkinsonian Striatum" International Journal of Molecular Sciences 23, no. 10: 5470. https://doi.org/10.3390/ijms23105470

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 Metrics

Abstract views Pdf views Html views

Article Menu

Non-Apoptotic Caspase-3 Activation Mediates Early Synaptic Dysfunction of Indirect Pathway Neurons in the Parkinsonian Striatum

Abstract

Supplementary Material

Share and Cite

Article Metrics

Article Access Statistics

Article Access Map by Country/Region

Further Information

Guidelines

MDPI Initiatives

Follow MDPI