Massive Loss of Proprioceptive Ia Synapses in Rat Spinal Motoneurons after Nerve Crush Injuries in the Postnatal Period
Arbat-Plana, Ariadna (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Bolívar Martín, Sara (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Navarro, X. (Xavier) (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Udina i Bonet, Esther (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Alvarez, Francisco J. (Emory University)

Fecha:	2023
Resumen:	Peripheral nerve injuries (PNIs) induce the retraction from the ventral horn of the synaptic collaterals of Ia afferents injured in the nerve, effectively removing Ia synapses from α-motoneurons. The loss of Ia input impairs functional recovery and could explain, in part, better recovery after PNIs with better Ia synaptic preservation. Synaptic losses correlate with injury severity, speed, and efficiency of muscle reinnervation and requires ventral microglia activation. It is unknown whether this plasticity is age dependent. In neonates, axotomized motoneurons and sensory neurons undergo apoptosis, but after postnatal day 10 most survive. The goal of this study was to analyze vesicular glutamate transporter 1 (VGluT1)-labeled Ia synapses (which also include II afferents) after nerve crush in 10 day old rats, a PNI causing little Ia/II synapse loss in adult rats. We confirmed fast and efficient reinnervation of leg muscles; however, a massive number of VGluT1/Ia/II synapses were permanently lost. This synapse loss was similar to that after more severe nerve injuries involving full transection in adults. In adults, disappearance of ventrally directed Ia/II collaterals targeting α-motoneurons was associated with a prolonged microglia reaction and a CCR2 mechanism that included infiltration of CCR2 blood immune cells. By contrast, microgliosis after P10 injuries was fast, resolved in about a week, and there was no evidence of peripheral immune cell infiltration. We conclude that VGluT1/Ia/II synapse loss in young animals differs in mechanism, perhaps associated with higher microglia synaptic pruning activity at this age and results in larger losses after milder nerve injuries.
Ayudas:	Agencia Estatal de Investigación RTI2018-096386-B-I00 Agencia Estatal de Investigación SAF2017-84464-R Ministerio de Sanidad y Consumo CB06/05/1105 Ministerio de Economía, Industria y Competitividad RD16/0011/0014
Nota:	Altres ajuts: NIH-NINDS R01 NS11196
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Ia afferent ; Microglia ; Motoneuron ; Neonates ; Nerve injury ; Plasticity
Publicado en:	eNeuro, Vol. 10 (february 2023) , ISSN 2373-2822

DOI: 10.1523/ENEURO.0436-22.2023
PMID: 36759186

19 p, 4.8 MB

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