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Importance of major histocompatibility complex of class I (MHC-I) expression for astroglial reactivity and stability of neural circuits in vitro.
Neurosci Lett. 2017 04 24; 647:97-103.NL

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 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.

Authors+Show Affiliations

Department of Structural and Functional Biology, Institute of Biology, University of Campinas - UNICAMP, Rua Monteiro Lobato, 255, CEP: 13083-865, Campinas, SP, Brazil.Department of Structural and Functional Biology, Institute of Biology, University of Campinas - UNICAMP, Rua Monteiro Lobato, 255, CEP: 13083-865, Campinas, SP, Brazil.Department of Structural and Functional Biology, Institute of Biology, University of Campinas - UNICAMP, Rua Monteiro Lobato, 255, CEP: 13083-865, Campinas, SP, Brazil.Department of Structural and Functional Biology, Institute of Biology, University of Campinas - UNICAMP, Rua Monteiro Lobato, 255, CEP: 13083-865, Campinas, SP, Brazil.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28341478

Citation

Bombeiro, André Luis, et al. "Importance of Major Histocompatibility Complex of Class I (MHC-I) Expression for Astroglial Reactivity and Stability of Neural Circuits in Vitro." Neuroscience Letters, vol. 647, 2017, pp. 97-103.
Bombeiro AL, Hell RC, Simões GF, et al. Importance of major histocompatibility complex of class I (MHC-I) expression for astroglial reactivity and stability of neural circuits in vitro. Neurosci Lett. 2017;647:97-103.
Bombeiro, A. L., Hell, R. C., Simões, G. F., Castro, M. V., & Oliveira, A. L. (2017). Importance of major histocompatibility complex of class I (MHC-I) expression for astroglial reactivity and stability of neural circuits in vitro. Neuroscience Letters, 647, 97-103. https://doi.org/10.1016/j.neulet.2017.03.038
Bombeiro AL, et al. Importance of Major Histocompatibility Complex of Class I (MHC-I) Expression for Astroglial Reactivity and Stability of Neural Circuits in Vitro. Neurosci Lett. 2017 04 24;647:97-103. PubMed PMID: 28341478.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Importance of major histocompatibility complex of class I (MHC-I) expression for astroglial reactivity and stability of neural circuits in vitro. AU - Bombeiro,André Luis, AU - Hell,Rafaela Chitarra Rodrigues, AU - Simões,Gustavo Ferreira, AU - Castro,Mateus Vidigal de, AU - Oliveira,Alexandre Leite Rodrigues de, Y1 - 2017/03/21/ PY - 2017/01/22/received PY - 2017/03/15/revised PY - 2017/03/20/accepted PY - 2017/3/28/pubmed PY - 2017/10/7/medline PY - 2017/3/26/entrez KW - Astrocytic reactivity KW - MHC-I KW - Neuron KW - Synapse KW - β2m silencing SP - 97 EP - 103 JF - Neuroscience letters JO - Neurosci. Lett. VL - 647 N2 - 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. SN - 1872-7972 UR - https://www.unboundmedicine.com/medline/citation/28341478/Importance_of_major_histocompatibility_complex_of_class_I__MHC_I__expression_for_astroglial_reactivity_and_stability_of_neural_circuits_in_vitro_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(17)30257-4 DB - PRIME DP - Unbound Medicine ER -