Modulation of central synapse remodeling after remote peripheral injuries by the CCL2-CCR2 axis and microglia

Travis M. Rotterman; Zoë Haley-Johnson; Tana S. Pottorf; Tavishi Chopra; Ethan Chang; Shannon Zhang; William M. McCallum; Sarah Fisher; Haley Franklin; Myriam Alvarez; Timothy C. Cope; Francisco J. Alvarez

doi:10.1016/j.celrep.2024.113776

Modulation of central synapse remodeling after remote peripheral injuries by the CCL2-CCR2 axis and microglia

Travis M. Rotterman, Zoë Haley-Johnson, Tana S. Pottorf, Tavishi Chopra, Ethan Chang, Shannon Zhang, William M. McCallum, Sarah Fisher, Haley Franklin, Myriam Alvarez, Timothy C. Cope, Francisco J. Alvarez

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Microglia-mediated synaptic plasticity after CNS injury varies depending on injury severity, but the mechanisms that adjust synaptic plasticity according to injury differences are largely unknown. This study investigates differential actions of microglia on essential spinal motor synaptic circuits following different kinds of nerve injuries. Following nerve transection, microglia and C-C chemokine receptor type 2 signaling permanently remove Ia axons and synapses from the ventral horn, degrading proprioceptive feedback during motor actions and abolishing stretch reflexes. However, Ia synapses and reflexes recover after milder injuries (nerve crush). These different outcomes are related to the length of microglia activation, being longer after nerve cuts, with slower motor-axon regeneration and extended expression of colony-stimulating factor type 1 in injured motoneurons. Prolonged microglia activation induces CCL2 expression, and Ia synapses recover after ccl2 is deleted from microglia. Thus, microglia Ia synapse removal requires the induction of specific microglia phenotypes modulated by nerve regeneration efficiencies. However, synapse preservation was not sufficient to restore the stretch-reflex function.

Original language	English (US)
Article number	113776
Journal	Cell Reports
Volume	43
Issue number	2
DOIs	https://doi.org/10.1016/j.celrep.2024.113776
State	Published - Feb 27 2024
Externally published	Yes

Keywords

C-C chemokine
colony stimulating factor 1
CP: Immunology
CP: Neuroscience
Ia afferent
motoneuron
nerve injury
neuroinflammation
regeneration
stretch reflex
synapse

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2024.113776

Cite this

Rotterman, T. M., Haley-Johnson, Z., Pottorf, T. S., Chopra, T., Chang, E., Zhang, S., McCallum, W. M., Fisher, S., Franklin, H., Alvarez, M., Cope, T. C., & Alvarez, F. J. (2024). Modulation of central synapse remodeling after remote peripheral injuries by the CCL2-CCR2 axis and microglia. Cell Reports, 43(2), Article 113776. https://doi.org/10.1016/j.celrep.2024.113776

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abstract = "Microglia-mediated synaptic plasticity after CNS injury varies depending on injury severity, but the mechanisms that adjust synaptic plasticity according to injury differences are largely unknown. This study investigates differential actions of microglia on essential spinal motor synaptic circuits following different kinds of nerve injuries. Following nerve transection, microglia and C-C chemokine receptor type 2 signaling permanently remove Ia axons and synapses from the ventral horn, degrading proprioceptive feedback during motor actions and abolishing stretch reflexes. However, Ia synapses and reflexes recover after milder injuries (nerve crush). These different outcomes are related to the length of microglia activation, being longer after nerve cuts, with slower motor-axon regeneration and extended expression of colony-stimulating factor type 1 in injured motoneurons. Prolonged microglia activation induces CCL2 expression, and Ia synapses recover after ccl2 is deleted from microglia. Thus, microglia Ia synapse removal requires the induction of specific microglia phenotypes modulated by nerve regeneration efficiencies. However, synapse preservation was not sufficient to restore the stretch-reflex function.",

keywords = "C-C chemokine, colony stimulating factor 1, CP: Immunology, CP: Neuroscience, Ia afferent, motoneuron, nerve injury, neuroinflammation, regeneration, stretch reflex, synapse",

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AU - Chopra, Tavishi

AU - Chang, Ethan

AU - Zhang, Shannon

AU - McCallum, William M.

AU - Fisher, Sarah

AU - Franklin, Haley

AU - Alvarez, Myriam

AU - Cope, Timothy C.

AU - Alvarez, Francisco J.

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N2 - Microglia-mediated synaptic plasticity after CNS injury varies depending on injury severity, but the mechanisms that adjust synaptic plasticity according to injury differences are largely unknown. This study investigates differential actions of microglia on essential spinal motor synaptic circuits following different kinds of nerve injuries. Following nerve transection, microglia and C-C chemokine receptor type 2 signaling permanently remove Ia axons and synapses from the ventral horn, degrading proprioceptive feedback during motor actions and abolishing stretch reflexes. However, Ia synapses and reflexes recover after milder injuries (nerve crush). These different outcomes are related to the length of microglia activation, being longer after nerve cuts, with slower motor-axon regeneration and extended expression of colony-stimulating factor type 1 in injured motoneurons. Prolonged microglia activation induces CCL2 expression, and Ia synapses recover after ccl2 is deleted from microglia. Thus, microglia Ia synapse removal requires the induction of specific microglia phenotypes modulated by nerve regeneration efficiencies. However, synapse preservation was not sufficient to restore the stretch-reflex function.

AB - Microglia-mediated synaptic plasticity after CNS injury varies depending on injury severity, but the mechanisms that adjust synaptic plasticity according to injury differences are largely unknown. This study investigates differential actions of microglia on essential spinal motor synaptic circuits following different kinds of nerve injuries. Following nerve transection, microglia and C-C chemokine receptor type 2 signaling permanently remove Ia axons and synapses from the ventral horn, degrading proprioceptive feedback during motor actions and abolishing stretch reflexes. However, Ia synapses and reflexes recover after milder injuries (nerve crush). These different outcomes are related to the length of microglia activation, being longer after nerve cuts, with slower motor-axon regeneration and extended expression of colony-stimulating factor type 1 in injured motoneurons. Prolonged microglia activation induces CCL2 expression, and Ia synapses recover after ccl2 is deleted from microglia. Thus, microglia Ia synapse removal requires the induction of specific microglia phenotypes modulated by nerve regeneration efficiencies. However, synapse preservation was not sufficient to restore the stretch-reflex function.

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Modulation of central synapse remodeling after remote peripheral injuries by the CCL2-CCR2 axis and microglia

Abstract

Keywords

ASJC Scopus subject areas

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