Abstract
We have shown previously, that mice lacking tumor necrosis factor-α(TNF-α) receptor 1 (TNFR1) exhibit greater hippocampal neurodegeneration, suggesting that TNFR1 may be protective in kainic acid (KA)-induced neurotoxicity. Here, we aim to clarify the role of TNF-α in neurodegenerative disorders and to elucidate its potential signaling pathways. TNF-αknockout (KO) mice and wild-type (WT) mice were treated with KA intranasally and, seizure severity measures obtained, Behavioral tests, including Elevated Plus-Maze™, open-field, Y-maze were also performed. Five days following KA treatment, immunohistochemical methods were used to assess neuronal degeneration and glial activation. The production of nitric oxide (NO) and the expression of nuclear factor kappaB (NF-κB) and AKT in the hippocampus were also measured. Compared with WT mice, TNF-α KO mice were more susceptibile to KA-induced neurotoxicity, as demonstrated by more severe seizures, measurable behavior changes, greater neuronal degeneration in hippocampus, elevated glial activation and NO production. Additionally, KA-treatment up-regulated the expression of NFκB in TNF-α KO mice to a greater degree than in KA-treated WT mice. We conclude that TNF-αdeficiency adversely influences KAinduced neurotoxicity and that TNF-αmay play a protective role in KA-induced neurotoxicity via the down-regulation of NFκB signaling pathway.
Keywords: TNF-α, kainic acid, neurotoxicity, hippocampus, NFκB.
Current Alzheimer Research
Title:Possible Protecting Role of TNF-α in Kainic Acid-induced Neurotoxicity Via Down-Regulation of NFκB Signaling Pathway
Volume: 10 Issue: 6
Author(s): Xing-Mei Zhang, Xiang-Yu Zheng, S. S. Sharkawi, Yang Ruan, Naheed Amir, Sheikh Azimullah, M. Y. Hasan, Jie Zhu and Abdu Adem
Affiliation:
Keywords: TNF-α, kainic acid, neurotoxicity, hippocampus, NFκB.
Abstract: We have shown previously, that mice lacking tumor necrosis factor-α(TNF-α) receptor 1 (TNFR1) exhibit greater hippocampal neurodegeneration, suggesting that TNFR1 may be protective in kainic acid (KA)-induced neurotoxicity. Here, we aim to clarify the role of TNF-α in neurodegenerative disorders and to elucidate its potential signaling pathways. TNF-αknockout (KO) mice and wild-type (WT) mice were treated with KA intranasally and, seizure severity measures obtained, Behavioral tests, including Elevated Plus-Maze™, open-field, Y-maze were also performed. Five days following KA treatment, immunohistochemical methods were used to assess neuronal degeneration and glial activation. The production of nitric oxide (NO) and the expression of nuclear factor kappaB (NF-κB) and AKT in the hippocampus were also measured. Compared with WT mice, TNF-α KO mice were more susceptibile to KA-induced neurotoxicity, as demonstrated by more severe seizures, measurable behavior changes, greater neuronal degeneration in hippocampus, elevated glial activation and NO production. Additionally, KA-treatment up-regulated the expression of NFκB in TNF-α KO mice to a greater degree than in KA-treated WT mice. We conclude that TNF-αdeficiency adversely influences KAinduced neurotoxicity and that TNF-αmay play a protective role in KA-induced neurotoxicity via the down-regulation of NFκB signaling pathway.
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Zhang Xing-Mei, Zheng Xiang-Yu, Sharkawi S. S., Ruan Yang, Amir Naheed, Azimullah Sheikh, Hasan Y. M., Zhu Jie and Adem Abdu, Possible Protecting Role of TNF-α in Kainic Acid-induced Neurotoxicity Via Down-Regulation of NFκB Signaling Pathway, Current Alzheimer Research 2013; 10 (6) . https://dx.doi.org/10.2174/15672050113109990007
DOI https://dx.doi.org/10.2174/15672050113109990007 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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