Modulator effects of interleukin-1beta and tumor necrosis factor-alpha on AMPA-induced excitotoxicity in mouse organotypic hippocampal slice cultures
| Autor: | Sara Xapelli, Liliana Bernardino, Jens Zimmer, Ana P. Silva, João O. Malva, Frantz Rom Poulsen, Annamaria Vezzani, Catarina R. Oliveira, Birthe Jakobsen |
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| Předmět: |
medicine.medical_treatment
Excitotoxicity Pharmacology medicine.disease_cause Hippocampus Mice 0302 clinical medicine Excitatory Amino Acid Agonists Drug Interactions Mice Knockout Neurons 0303 health sciences Microglia Cell Death General Neuroscience Glutamate receptor Neuroprotection medicine.anatomical_structure Cytokine Receptors Tumor Necrosis Factor Type I Cytokines Tumor necrosis factor alpha Glutamate Cell Survival Neurotoxins Glutamic Acid AMPA receptor Biology Proinflammatory cytokine 03 medical and health sciences Organ Culture Techniques Neurobiology of Disease medicine Animals Receptors Tumor Necrosis Factor Type II Receptors AMPA Neurodegeneration alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid 030304 developmental biology Inflammation Dose-Response Relationship Drug Tumor Necrosis Factor-alpha Mice Inbred C57BL nervous system Immunology Nerve Degeneration 030217 neurology & neurosurgery Interleukin-1 |
| Zdroj: | CIÊNCIAVITAE Bernardino, L, Xapelli, S, Silva, A P, Jakobsen, B, Poulsen, F R, Oliveira, C R, Vezzani, A, Malva, J O & Zimmer, J 2005, ' Modulator effects of interleukin-1beta and tumor necrosis factor-alpha on AMPA-induced excitotoxicity in mouse organotypic hippocampal slice cultures. ', Journal of Neuroscience, vol. 25, no. 29, pp. 6734-44 . https://doi.org/10.1523/JNEUROSCI.1510-05.2005 Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP |
| DOI: | 10.1523/JNEUROSCI.1510-05.2005 |
| Popis: | Udgivelsesdato: 2005-Jul-20 The inflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha (TNF-alpha) have been identified as mediators of several forms of neurodegeneration in the brain. However, they can produce either deleterious or beneficial effects on neuronal function. We investigated the effects of these cytokines on neuronal death caused by exposure of mouse organotypic hippocampal slice cultures to toxic concentrations of AMPA. Either potentiation of excitotoxicity or neuroprotection was observed, depending on the concentration of the cytokines and the timing of exposure. A relatively high concentration of mouse recombinant TNF-alpha (10 ng/ml) enhanced excitotoxicity when the cultures were simultaneously exposed to AMPA and to this cytokine. Decreasing the concentration of TNF-alpha to 1 ng/ml resulted in neuroprotection against AMPA-induced neuronal death independently on the application protocol. By using TNF-alpha receptor (TNFR) knock-out mice, we demonstrated that the potentiation of AMPA-induced toxicity by TNF-alpha involves TNF receptor-1, whereas the neuroprotective effect is mediated by TNF receptor-2. AMPA exposure was associated with activation and proliferation of microglia as assessed by macrophage antigen-1 and bromodeoxyuridine immunohistochemistry, suggesting a functional recruitment of cytokine-producing cells at sites of neurodegeneration. Together, these findings are relevant for understanding the role of proinflammatory cytokines and microglia activation in acute and chronic excitotoxic conditions. |
| Databáze: | OpenAIRE |
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