The synaptic blocker botulinum toxin A decreases the density and complexity of oligodendrocyte precursor cells in the adult mouse hippocampus
The synaptic blocker botulinum toxin A decreases the density and complexity of oligodendrocyte precursor cells in the adult mouse hippocampus
Oligodendrocyte progenitor cells (OPCs) are responsible for generating oligodendrocytes, the myelinating cells of the CNS. Life-long myelination is promoted by neuronal activity and is essential for neural network plasticity and learning. OPCs are known to contact synapses and it is proposed that neuronal synaptic activity in turn regulates their behavior. To examine this in the adult, we performed unilateral injection of the synaptic blocker botulinum neurotoxin A (BoNT/A) into the hippocampus of adult mice. We confirm BoNT/A cleaves SNAP-25 in the CA1 are of the hippocampus, which has been proven to block neurotransmission. Notably, BoNT/A significantly decreased OPC density and caused their shrinkage, as determined by immunolabeling for the OPC marker NG2. Furthermore, BoNT/A resulted in an overall decrease in the number of OPC processes, as well as a decrease in their lengths and branching frequency. These data indicate that synaptic activity is important for maintaining adult OPC numbers and cellular integrity, which is relevant to pathophysiological scenarios characterized by dysregulation of synaptic activity, such as age-related cognitive decline, Multiple Sclerosis and Alzheimer's disease.
BoNT/A, RRID:AB_11213678, RRID:AB_143165, RRID:AB_2313606, RRID:AB_2340613, RRID:SCR_002798, RRID:SCR_003070, RRID:SCR_016788, RRID:SCR_017348, SNAP-25, SNARE, Synapse, botulinum toxin A, hippocampus, mouse, oligodendrocyte progenitor cell
2216-2227
Chacon-De-La-Rocha, Irene
8645027e-ee17-474c-9396-35c25ed65cad
Fryatt, Gemma L
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Rivera, Andrea D
86ac60f6-43fc-45c5-8922-6ba1f25242d7
Restani, Laura
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Caleo, Matteo
f40884a6-2b30-4dc8-bbb8-47dfdc5cf2bc
Gomez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5
Butt, Arthur M
381a0c45-e817-4f3c-90d9-3f8cf020fd12
September 2021
Chacon-De-La-Rocha, Irene
8645027e-ee17-474c-9396-35c25ed65cad
Fryatt, Gemma L
afd66d34-31f7-4231-9a7c-50bc283646bd
Rivera, Andrea D
86ac60f6-43fc-45c5-8922-6ba1f25242d7
Restani, Laura
6c20fd33-f21d-491b-bd4f-e37846571393
Caleo, Matteo
f40884a6-2b30-4dc8-bbb8-47dfdc5cf2bc
Gomez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5
Butt, Arthur M
381a0c45-e817-4f3c-90d9-3f8cf020fd12
Chacon-De-La-Rocha, Irene, Fryatt, Gemma L, Rivera, Andrea D, Restani, Laura, Caleo, Matteo, Gomez-Nicola, Diego and Butt, Arthur M
(2021)
The synaptic blocker botulinum toxin A decreases the density and complexity of oligodendrocyte precursor cells in the adult mouse hippocampus.
Journal of Neuroscience Research, 99 (9), .
(doi:10.1002/jnr.24856).
Abstract
Oligodendrocyte progenitor cells (OPCs) are responsible for generating oligodendrocytes, the myelinating cells of the CNS. Life-long myelination is promoted by neuronal activity and is essential for neural network plasticity and learning. OPCs are known to contact synapses and it is proposed that neuronal synaptic activity in turn regulates their behavior. To examine this in the adult, we performed unilateral injection of the synaptic blocker botulinum neurotoxin A (BoNT/A) into the hippocampus of adult mice. We confirm BoNT/A cleaves SNAP-25 in the CA1 are of the hippocampus, which has been proven to block neurotransmission. Notably, BoNT/A significantly decreased OPC density and caused their shrinkage, as determined by immunolabeling for the OPC marker NG2. Furthermore, BoNT/A resulted in an overall decrease in the number of OPC processes, as well as a decrease in their lengths and branching frequency. These data indicate that synaptic activity is important for maintaining adult OPC numbers and cellular integrity, which is relevant to pathophysiological scenarios characterized by dysregulation of synaptic activity, such as age-related cognitive decline, Multiple Sclerosis and Alzheimer's disease.
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More information
Accepted/In Press date: 2021
e-pub ahead of print date: 29 May 2021
Published date: September 2021
Additional Information:
Funding Information:
We thank Dr Olivier Raineteau for assistance and use of Neurolucida in the INSERM Stem Cell and Brain Research Institute, Univ Lyon, France. The research presented in this paper was supported by grants from the BBSRC (AB, Grant Number BB/M029379/1), MRC (AB, Grant Number MR/P025811/1), Alzheimer's Research UK (DG‐N, AB, Grant Number PG2014B‐2), University of Portsmouth PhD Programme (AB, ICR), and CNR – Joint Laboratories (MC, LR).
Funding Information:
We thank Dr Olivier Raineteau for assistance and use of Neurolucida in the INSERM Stem Cell and Brain Research Institute, Univ Lyon, France. The research presented in this paper was supported by grants from the BBSRC (AB, Grant Number BB/M029379/1), MRC (AB, Grant Number MR/P025811/1), Alzheimer's Research UK (DG-N, AB, Grant Number PG2014B-2), University of Portsmouth PhD Programme (AB, ICR), and CNR ? Joint Laboratories (MC, LR).
Publisher Copyright:
© 2021 The Authors. Journal of Neuroscience Research published by Wiley Periodicals LLC.
Keywords:
BoNT/A, RRID:AB_11213678, RRID:AB_143165, RRID:AB_2313606, RRID:AB_2340613, RRID:SCR_002798, RRID:SCR_003070, RRID:SCR_016788, RRID:SCR_017348, SNAP-25, SNARE, Synapse, botulinum toxin A, hippocampus, mouse, oligodendrocyte progenitor cell
Identifiers
Local EPrints ID: 449593
URI: http://eprints.soton.ac.uk/id/eprint/449593
ISSN: 0360-4012
PURE UUID: ff27779b-8f2a-41f9-9954-b6736e98efba
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Date deposited: 08 Jun 2021 16:32
Last modified: 17 Mar 2024 03:22
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Contributors
Author:
Irene Chacon-De-La-Rocha
Author:
Andrea D Rivera
Author:
Laura Restani
Author:
Matteo Caleo
Author:
Arthur M Butt
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