Importance of major histocompatibility complex of class I (MHC-I) expression for astroglial reactivity and stability of neural circuits in vitro
Autor: | Alexandre Leite Rodrigues de Oliveira, Mateus Vidigal de Castro, Gustavo Ferreira Simões, Rafaela C.R. Hell, André Luis Bombeiro |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Synaptic cleft Synaptogenesis chemical and pharmacologic phenomena Biology Synapse 03 medical and health sciences 0302 clinical medicine Neurotrophic factors MHC class I medicine Animals Glial Cell Line-Derived Neurotrophic Factor Gliosis RNA Messenger Neurons General Neuroscience Brain-Derived Neurotrophic Factor Histocompatibility Antigens Class I medicine.disease Coculture Techniques Astrogliosis Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Spinal Cord Astrocytes Synaptic plasticity Synapses biology.protein Cytokines RNA Interference beta 2-Microglobulin Neuroscience 030217 neurology & neurosurgery Astrocyte |
Zdroj: | Neuroscience letters. 647 |
ISSN: | 1872-7972 |
Popis: | 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 expression60%, p0.001). As measured by qRT-PCR, silencing of β2m decreased expression of the astrocytic marker GFAP (60%, p0.001), 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. |
Databáze: | OpenAIRE |
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