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Article

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

1
Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, 223 62 Lund, Sweden
2
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)
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 Parkinson’s disease; striatum; caspase-3; spiny projection neurons; dendritic spines; long-term depression; Q-VD-OPh; mice
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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

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