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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
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
0360-4012
2216-2227
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
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), 2216-2227. (doi:10.1002/jnr.24856).

Record type: Article

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
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
ORCID for Diego Gomez-Nicola: ORCID iD orcid.org/0000-0002-5316-2682

Catalogue record

Date deposited: 08 Jun 2021 16:32
Last modified: 26 Nov 2021 02:56

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Contributors

Author: Irene Chacon-De-La-Rocha
Author: Gemma L Fryatt
Author: Andrea D Rivera
Author: Laura Restani
Author: Matteo Caleo
Author: Arthur M Butt

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