Importance of major histocompatibility complex of class I (MHC-I) expression for astroglial reactivity and stability of neural circuits in vitro

Author(s)

Bombeiro, Andre Luis ; Rodrigues Hell, Rafaela Chitarra ; Simoes, Gustavo Ferreira ; de Castro, Mateus Vidigal ; Rodrigues de Oliveira, Alexandre Leite

• Document type: Journal article
• Source: Neuroscience Letters; v. 647, p. 97-103, APR 24 2017.
• Web of Science Citations: 3

Abstract

MHC-I molecules are involved in the antigenic presentation of cytosol-derived peptides to CD8T lymphocytes. In the nervous system, MHC-I expression is low to absent, occurring only during certain phases of development and aging or after injuries. The involvement of MHC-I in synaptic plasticity has been reported and, following lesion, astrocytes become reactive, limiting tissue damage. Such cells also attempt to restore homeostasis by secreting cytokines and neurotrophic factors. Moreover, astrocytes modulate synapse function, by taking up and releasing neurotransmitters and by limiting the synaptic cleft. Thus, the aim of the present study was to evaluate if astrocyte activation and reactivity are related to MHC I expression and if astrogliosis can be downregulated by silencing MHC-I mRNA synthesis. Given that, we evaluated astrocyte reactivity and synaptogenesis in co-cultures of astrocytes and spinal neurons under MHC-I RNA interference. For that, the MHC-I beta 2-microglobulin subunit (beta 2m) was knocked-down by siRNA in co-cultures (beta 2m expression <60%, p < 0.001). As measured by qRT-PCR, silencing of beta 2m decreased expression of the astrocytic marker GFAP (<60%, p < 0.001), as well as neurotrophic factors (BDNF and GDNF) and pro-inflammatory cytokines (TNF-alpha, IL-1, IL-6, IL-12 and IL-17). No significant changes in synaptic stability indicate that neuron-neuron interaction was preserved after beta 2m silencing. Overall, the present data reinforce the importance of MHC-I expression for generation of astrogliosis, what may, in turn, become a target for future CNS/PNS therapies following injury. (C) 2017 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 11/08123-9 - Relative importance of glial reactivity and expression of MHC Class I for the maintenance of neuronal circuits in vitro
• Grantee: Alexandre Leite Rodrigues de Oliveira
• Support Opportunities: Regular Research Grants
• 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: 10/05370-2 - Role of glial reactivity and expression of MHC class I in the maintenance of neuronal circuits in vitro
• Grantee: Rafaela Chitarra Rodrigues Hell
• Support Opportunities: Scholarships in Brazil - Post-Doctoral