Importance of major histocompatibility complex of class I (MHC-I) expression for astroglial reactivity and stability of neural circuits in vitro.
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 β2-microglobulin subunit (β2m) was knocked-down by siRNA in co-cultures (β2m expression <60%, p<0.001). As measured by qRT-PCR, silencing of β2m decreased expression of the astrocytic marker GFAP (<60%, p<0.001), as well as neurotrophic factors (BDNF and GDNF) and pro-inflammatory cytokines (TNF-α, IL-1, IL-6, IL-12 and IL-17). No significant changes in synaptic stability indicate that neuron-neuron interaction was preserved after β2m 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.
Department of Structural and Functional Biology, Institute of Biology, University of Campinas - UNICAMP, Rua Monteiro Lobato, 255, CEP: 13083-865, Campinas, SP, Brazil.
André Luis
AL
Bombeiro
Department of Structural and Functional Biology, Institute of Biology, University of Campinas - UNICAMP, Rua Monteiro Lobato, 255, CEP: 13083-865, Campinas, SP, Brazil.
Rafaela Chitarra Rodrigues
RC
Hell
Department of Structural and Functional Biology, Institute of Biology, University of Campinas - UNICAMP, Rua Monteiro Lobato, 255, CEP: 13083-865, Campinas, SP, Brazil.
Gustavo Ferreira
GF
Simões
Department of Structural and Functional Biology, Institute of Biology, University of Campinas - UNICAMP, Rua Monteiro Lobato, 255, CEP: 13083-865, Campinas, SP, Brazil.
Mateus Vidigal de
MV
Castro
Department of Structural and Functional Biology, Institute of Biology, University of Campinas - UNICAMP, Rua Monteiro Lobato, 255, CEP: 13083-865, Campinas, SP, Brazil. Electronic address: alroliv@unicamp.br.
Alexandre Leite Rodrigues de
AL
Oliveira
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D005911:Gliosis; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D013569:Synapses / Q000502:physiology; D001613:beta 2-Microglobulin / Q000235:genetics
D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D051100:Glial Cell Line-Derived Neurotrophic Factor; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger; D001613:beta 2-Microglobulin
Astrocytic reactivity; MHC-I; Neuron; Synapse; β2m silencing