Glatiramer acetate positively influences spinal motoneuron survival and synaptic plasticity after ventral root avulsion.
Avulsion of ventral roots induces degeneration of most axotomized motoneurons. At present there are no effective strategies to prevent such neuronal loss and to preserve the affected spinal circuits. Interestingly, changes in the spinal cord network also occur during the course of the experimental model of multiple sclerosis (experimental autoimmune encephalomyelitis-EAE). Glatiramer acetate (GA) significantly reduces the seriousness of the symptoms during the exacerbation of EAE. However, little is known about its effects on motoneurons. In the present study, we investigated whether GA has an influence on synapse plasticity and glial reaction after ventral root avulsion (VRA). Lewis rats were subjected to the avulsion of lumbar ventral roots and treated with GA. The animals were sacrificed after 14 days of treatment and the spinal cords processed for immunohistochemistry. A correlation between the synaptic changes and glial activation was obtained by performing immunolabeling against synaptophysin, GFAP and Iba-1. GA treatment preserved synaptophysin labeling, and significantly reduced the glial reaction in the area surrounding the axotomized motoneurons. After ventral root avulsion, GA treatment was also neuroprotective. The present results indicate that the immunomodulator GA has an influence on the stability of nerve terminals in the spinal cord, which may in turn contribute to future treatment strategies after proximal lesions to spinal motoneurons.
Scorisa
Juliana Milani
JM
Dept. of Anatomy - Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil.
Zanon
Renata Graciele
RG
Freria
Camila Marques
CM
de Oliveira
Alexandre Leite Rodrigues
AL
D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D000068717:Glatiramer Acetate; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis / Q000378:metabolism; D005911:Gliosis / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D008840:Microfilament Proteins; D009046:Motor Neurons / Q000187:drug effects* / Q000473:pathology; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D019051:Rhizotomy / Q000009:adverse effects*; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013126:Spinal Nerve Roots / Q000293:injuries / Q000473:pathology / Q000503:physiopathology; D016708:Synaptophysin / Q000032:analysis / Q000378:metabolism
C100745:Aif1 protein, rat; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D007166:Immunosuppressive Agents; D008840:Microfilament Proteins; D018696:Neuroprotective Agents; D010455:Peptides; D016708:Synaptophysin; D000068717:Glatiramer Acetate