Kynurenic Acid Prevents Cytoskeletal Disorganization Induced by Quinolinic Acid in Mixed Cultures of Rat Striatum
| Autor: | Angela T. S. Wyse, Regina Pessoa-Pureur, Fernanda Silva Ferreira, Paula Pierozan, Helena Biasibetti-Brendler, Felipe Schmitz |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
N-Methylaspartate Neuroscience (miscellaneous) Cell Communication Biology Kynurenic Acid Cell morphology Models Biological Antioxidants 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Kynurenic acid Downregulation and upregulation medicine Animals Rats Wistar Cytoskeleton Cells Cultured Neurons Microglia Tumor Necrosis Factor-alpha Gap Junctions Quinolinic Acid Corpus Striatum Cell biology Oxidative Stress 030104 developmental biology medicine.anatomical_structure Neurology chemistry Biochemistry Astrocytes Neuron Dizocilpine Maleate 030217 neurology & neurosurgery Signal Transduction Astrocyte Quinolinic acid |
| Zdroj: | Molecular Neurobiology. 55:5111-5124 |
| ISSN: | 1559-1182 0893-7648 |
| DOI: | 10.1007/s12035-017-0749-2 |
| Popis: | Kynurenic acid (KYNA) is a neuroactive metabolite of tryptophan known to modulate a number of mechanisms involved in neural dysfunction. Although its activity in the brain has been widely studied, the effect of KYNA counteracting the actions of quinolinic acid (QUIN) remains unknown. The present study aims at describing the ability of 100 μM KYNA preventing cytoskeletal disruption provoked by QUIN in astrocyte/neuron/microglia mixed culture. KYNA totally preserved cytoskeletal organization, cell morphology, and redox imbalance in mixed cultures exposed to QUIN. However, KYNA partially prevented morphological alteration in isolated primary astrocytes and failed to protect the morphological alterations of neurons caused by QUIN exposure. Moreover, KYNA prevented QUIN-induced microglial activation and upregulation of ionized calcium-binding adapter molecule 1 (Iba-1) and partially preserved tumor necrosis factor-α (TNF-α) level in mixed cultures. TNF-α level was also partially preserved in astrocytes. In addition to the mechanisms dependent on redox imbalance and microglial activation, KYNA prevented downregulation of connexin-43 and the loss of functionality of gap junctions (GJs), preserving cell-cell contact, cytoskeletal organization, and cell morphology in QUIN-treated cells. Furthermore, the toxicity of QUIN targeting the cytoskeleton of mixed cultures was not prevented by the N-methyl-D-aspartate (NMDA) antagonist MK-801. We suggest that KYNA protects the integrity of the cytoskeleton of mixed cultures by complex mechanisms including modulating microglial activation preventing oxidative imbalance and misregulated GJs leading to disrupted cytoskeleton in QUIN-treated cells. This study contributed to elucidate the molecular basis of KYNA protection against QUIN toxicity. |
| Databáze: | OpenAIRE |
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