1. Modulation of central synapse remodeling after remote peripheral injuries by the CCL2-CCR2 axis and microglia.
- Author
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Rotterman, Travis M., Haley-Johnson, Zoë, Pottorf, Tana S., Chopra, Tavishi, Chang, Ethan, Zhang, Shannon, McCallum, William M., Fisher, Sarah, Franklin, Haley, Alvarez, Myriam, Cope, Timothy C., and Alvarez, Francisco J.
- 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. [Display omitted] • Preservation of the stretch-reflex circuit after nerve injuries varies with injury severity • More severe injuries activate microglia for longer because of continuous CSF1 availability • Extended microglia activation induces CCL2 expression and pro-inflammatory properties • CCL2 deletion from microglia rescues stretch-reflex synapses but not their function Rotterman et al. show that peripheral nerve injury severity modulates microglia activation in the ventral horn of the spinal cord, which transforms spinal networks controlling motor function. Specifically, CCL2-expressing microglia are induced after more severe injuries, causing permanent removal of synapses carrying proprioceptive information necessary for fine movement coordination. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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