Role of MHC-I Expression on Spinal Motoneuron Survival and Glial Reactions Following Ventral Root Crush in Mice

Author(s)

Cartarozzi, Luciana Politti ^[1] ; Perez, Matheus ^[2] ; Kirchhoff, Frank ^[3] ; Rodrigues de Oliveira, Alexandre Leite ^[1]

Affiliation

^[1] Univ Estadual Campinas, UNICAMP, Lab Nerve Regenerat, Cidade Univ Zeferino Vaz, Rua Monteiro Lobato 255, BR-13083970 Campinas, SP - Brazil

^[2] Univ Sao Paulo, Sch Phys Educ & Sport Ribeirao Preto, Av Bandeirantes 3900, BR-14040907 Ribeirao Preto, SP - Brazil

^[3] Univ Saarland, Ctr Integrat Physiol & Mol Med, Mol Physiol, Bldg 48, D-66421 Homburg - Germany

• Document type: Journal article
• Source: CELLS; v. 8, n. 5 MAY 2019.
• Web of Science Citations: 1

Abstract

Lesions to the CNS/PNS interface are especially severe, leading to elevated neuronal degeneration. In the present work, we establish the ventral root crush model for mice, and demonstrate the potential of such an approach, by analyzing injury evoked motoneuron loss, changes of synaptic coverage and concomitant glial responses in 2-microglobulin knockout mice (2m KO). Young adult (8-12 weeks old) C57BL/6J (WT) and 2m KO mice were submitted to a L4-L6 ventral roots crush. Neuronal survival revealed a time-dependent motoneuron-like cell loss, both in WT and 2m KO mice. Along with neuronal loss, astrogliosis increased in WT mice, which was not observed in 2m KO mice. Microglial responses were more pronounced during the acute phase after lesion and decreased over time, in WT and KO mice. At 7 days after lesion 2m KO mice showed stronger Iba-1(+) cell reaction. The synaptic inputs were reduced over time, but in 2m KO, the synaptic loss was more prominent between 7 and 28 days after lesion. Taken together, the results herein demonstrate that ventral root crushing in mice provides robust data regarding neuronal loss and glial reaction. The retrograde reactions after injury were altered in the absence of functional MHC-I surface expression. (AU)

• FAPESP's process: 14/06892-3 - Use of mesenchymal stem cells in the CNS/PNS interface: repair of proximal lesions
• Grantee: Alexandre Leite Rodrigues de Oliveira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/16134-6 - Immunomodulatory mechanisms of mesenchymal stem cells in glial reactivity and correlation with nervous system regenerative capacity after lumbar root axotomy
• Grantee: Luciana Politti Cartarozzi
• Support Opportunities: Scholarships in Brazil - Doctorate