Non‐Apoptotic Caspase‐3 Activation Mediates Early Synaptic Dysfunction of Indirect Pathway Neurons in the Parkinsonian Striatum
Fieblinger, Tim LU ; Li, Chang LU ; Espa, Elena LU and Cenci, M. Angela LU
(2022)
In International Journal of Molecular Sciences
23(10).
- 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... (More)
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.
(Less)
- author
- Fieblinger, Tim
LU
; Li, Chang
LU
; Espa, Elena
LU
and Cenci, M. Angela
LU
- organization
- publishing date
- 2022
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- caspase‐3, dendritic spines, long‐term depression, mice, Parkinson’s disease, Q‐VD‐OPh, spiny projection neurons, striatum
- in
- International Journal of Molecular Sciences
- volume
- 23
- issue
- 10
- article number
- 5470
- publisher
- MDPI AG
- external identifiers
-
- pmid:35628278
- scopus:85129819515
- ISSN
- 1661-6596
- DOI
- 10.3390/ijms23105470
- language
- English
- LU publication?
- yes
- id
- 333be26a-b598-48e8-a91a-1d607c953d61
- date added to LUP
- 2022-07-14 15:05:16
- date last changed
- 2024-04-18 08:57:08
@article{333be26a-b598-48e8-a91a-1d607c953d61,
abstract = {{<p>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.</p>}},
author = {{Fieblinger, Tim and Li, Chang and Espa, Elena and Cenci, M. Angela}},
issn = {{1661-6596}},
keywords = {{caspase‐3; dendritic spines; long‐term depression; mice; Parkinson’s disease; Q‐VD‐OPh; spiny projection neurons; striatum}},
language = {{eng}},
number = {{10}},
publisher = {{MDPI AG}},
series = {{International Journal of Molecular Sciences}},
title = {{Non‐Apoptotic Caspase‐3 Activation Mediates Early Synaptic Dysfunction of Indirect Pathway Neurons in the Parkinsonian Striatum}},
url = {{http://dx.doi.org/10.3390/ijms23105470}},
doi = {{10.3390/ijms23105470}},
volume = {{23}},
year = {{2022}},
}