Role of γ-aminobutyric acid B (GABAB) receptors in the regulation of kainic acid-induced cell death in mouse hippocampus

Lee, Han Kyu; Seo, Young‐Joon; Choi, Seong Hun; Kwon, Min Soo; Shim, Eon Jeong; Lee, Jin Young; Suh, Hwal

doi:10.1038/emm.2005.66

Cited by 9 publications

(5 citation statements)

References 58 publications

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“…Moreover, activated astrocytes, mediators of the inflammatory response, promote the release of proinflammatory cytokines, which extends brain damage and contributes to behavioral changes and neuronal damage initiated by activation of KA receptors. Several studies in recent years have demonstrated that ERK signaling is activated in a model of KA-induced excitotoxicity (46,47). Furthermore, we also observed that C/EBP b upregulation in the hippocampus of DA-treated mice is disrupted by i.c.v.…”

Section: Discussionsupporting

confidence: 60%

Troxerutin Counteracts Domoic Acid–Induced Memory Deficits in Mice by Inhibiting CCAAT/Enhancer Binding Protein β–Mediated Inflammatory Response and Oxidative Stress

Lü

Zheng

et al. 2013

The Journal of Immunology

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The C/EBP β is a basic leucine zipper transcription factor that regulates a variety of biological processes, including metabolism, cell proliferation and differentiation, and immune response. Recent findings show that C/EBP β–induced inflammatory responses mediate kainic acid–triggered excitotoxic brain injury. In this article, we show that protein kinase C ζ enhances K-ras expression and subsequently activates the Raf/MEK/ERK1/2 pathway in the hippocampus of domoic acid (DA)–treated mice, which promotes C/EBP β expression and induces inflammatory responses. Elevated production of TNF-α impairs mitochondrial function and increases the levels of reactive oxygen species by IκB kinase β/NF-κB signaling. The aforementioned inflammation and oxidative stress lead to memory deficits in DA-treated mice. However, troxerutin inhibits cyclin-dependent kinase 1 expression, enhances type 1 protein phosphatase α dephosphorylation, and abolishes MEK/ERK1/2/C/EBP β activation, which subsequently reverses the memory impairment observed in the DA-treated mice. Thus, troxerutin is recommended as a potential candidate for the prevention and therapeutic treatment of cognitive deficits resulting from excitotoxic brain damage and other brain disorders.

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Section: Discussionsupporting

confidence: 60%

Troxerutin Counteracts Domoic Acid–Induced Memory Deficits in Mice by Inhibiting CCAAT/Enhancer Binding Protein β–Mediated Inflammatory Response and Oxidative Stress

Lü

Zheng

et al. 2013

The Journal of Immunology

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“…Kainic acid (KA) is a potent glutamate receptor agonist with selectivity towards non-N-methyl-D-aspartate (NMDA)-type glutamate receptors [3;4]. KA is well known for its ability to induce seizures within minutes of its administration and is followed by a delayed excitotoxic neuron death in the hippocampus several hours later, in part through an increase in intracellular calcium and activation of calcium-dependent neuron death pathways [5][6][7]. Both apoptotic and necrotic death of neurons Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication.…”

Section: Introductionmentioning

confidence: 99%

Kainic acid induces early and transient autophagic stress in mouse hippocampus

Shacka

Lü

Xie

et al. 2007

Neuroscience Letters

105

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Kainic acid (KA) treatment is a well-established model of hippocampal neuron death mediated in large part by KA receptor-induced excitotoxicity. KA-induced, delayed neuron death has been shown previously to follow the induction of seizures and exhibit characteristics of both apoptosis and necrosis. Growing evidence supports a role of autophagic stress-induced death of neurons in several in vitro and in vivo models of neuron death and neurodegeneration. However, whether autophagic stress also plays a role in KA-induced excitotoxicity has not been previously investigated. To examine whether KA alters the levels of proteins associated with or known to regulate the formation of autophagic vacuoles, we isolated hippocampal extracts from control mice and in mice following 2-16h KA injection. KA induced a significant increase in the amount of LC3-II, a specific marker of autophagic vacuoles, at 4-6h following KA, which indicates a transient induction of autophagic stress. Levels of autophagy-associated proteins including ATG5 (conjugated to ATG12), ATG6 and ATG7 did not change significantly after treatment with KA. However, ratios of phospho-mTOR/ mTOR were elevated from 6-16h, and ratios of phospho-Akt/Akt were elevated at 16h following KA treatment, suggesting a potential negative feedback loop to inhibit further stimulation of autophagic stress. Together these data indicate the transient induction of autophagic stress by KA which may serve to regulate excitotoxic death in mouse hippocampus. Keywords kainic acid; hippocampus; autophagy; ATG5; ATG7; Akt; mTOR; LC3The excitatory amino acid neurotransmitter glutamate is known to play an important role in a vast array of neuronal activities as well as in the induction of excitotoxic neurodegeneration through massive activation of its receptors [1;2]. Kainic acid (KA) is a potent glutamate receptor agonist with selectivity towards non-N-methyl-D-aspartate (NMDA)-type glutamate receptors [3;4]. KA is well known for its ability to induce seizures within minutes of its administration and is followed by a delayed excitotoxic neuron death in the hippocampus several hours later, in part through an increase in intracellular calcium and activation of calcium-dependent neuron death pathways [5][6][7]. Both apoptotic and necrotic death of neurons Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Autophagic stress results from alterations in autophagy, a lysosomal degradation pathway that is responsible for the homeostatically regulated turnover of macronutrients and organelles [10]. Macroautophagy, the most prominent form of autophagy ...

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“…[36][37][38] Upon binding to non-NMDA glutamate receptors, KA provokes depolarization of neurons followed by severe status epilepticus, neurodegeneration, memory loss, neuronal cell death. [39][40] The possible role of NMDA and non-NMDA receptors in the regulation of neurotoxic responses (lethality, memory loss, hippocampal cell death, signal transduction systems), stimulated by KA was discussed by Lee et al 41 The neuronal degeneration after KA administration is generally accepted to be associated with a depletion of ATP and accumulation of [Ca 2þ ] i.…”

Section: Discussionmentioning

confidence: 99%

Are nociceptin(1‐13)NH₂and its structural analogue [ORN⁹]nociceptin(1‐13)NH₂able to affect brain antioxidant status in control and kainic acid‐treated rats?

Tsvetanova

Павлова

Alexandrova

et al. 2009

Cell Biochemistry & Function

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In-vivo effects of nociceptin (N/OFQ(1-13)NH(2)) on the levels of lipid peroxidation and cell enzyme (superoxide dismutase, glutathione peroxidase and glutathione reductase) and non-enzyme (glutathione) antioxidants in brain of control and kainic acid-treated rats were studied. N/OFQ(1-13)NH(2) effects were compared with those of its structural analogue [Orn(9)]N/OFQ(1-13)NH(2). Kainic acid (25 microg, i.c.v) increased the lipid peroxidation (4 and 24 h after kainic acid treatment) and decreased the glutathione level (1 h after kainic acid injection). We failed to find, any changes in antioxidant enzyme activities, independently of the time of kainic acid treatment. At the background of kainic acid-effects, N/OFQ(1-13)NH(2) and [Orn(9)] N/OFQ(1-13)NH(2), injected 30 min before kainic acid, had no effects on all parameters, tested in brain. In addition, the neuropeptides did not change the antioxidant status in brain of control animals. It might be concluded that N/OFQ(1-13)NH(2) and [Orn(9)]N/OFQ(1-13)NH(2) have neither pro- nor anti-oxidant activity.

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Role of γ-aminobutyric acid B (GABAB) receptors in the regulation of kainic acid-induced cell death in mouse hippocampus

Abstract: Abstract

Cited by 9 publications

References 58 publications

Troxerutin Counteracts Domoic Acid–Induced Memory Deficits in Mice by Inhibiting CCAAT/Enhancer Binding Protein β–Mediated Inflammatory Response and Oxidative Stress

Troxerutin Counteracts Domoic Acid–Induced Memory Deficits in Mice by Inhibiting CCAAT/Enhancer Binding Protein β–Mediated Inflammatory Response and Oxidative Stress

Kainic acid induces early and transient autophagic stress in mouse hippocampus

Are nociceptin(1‐13)NH₂and its structural analogue [ORN⁹]nociceptin(1‐13)NH₂able to affect brain antioxidant status in control and kainic acid‐treated rats?

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Role of γ-aminobutyric acid B (GABAB) receptors in the regulation of kainic acid-induced cell death in mouse hippocampus

Abstract: Abstract

Cited by 9 publications

References 58 publications

Troxerutin Counteracts Domoic Acid–Induced Memory Deficits in Mice by Inhibiting CCAAT/Enhancer Binding Protein β–Mediated Inflammatory Response and Oxidative Stress

Troxerutin Counteracts Domoic Acid–Induced Memory Deficits in Mice by Inhibiting CCAAT/Enhancer Binding Protein β–Mediated Inflammatory Response and Oxidative Stress

Kainic acid induces early and transient autophagic stress in mouse hippocampus

Are nociceptin(1‐13)NH2and its structural analogue [ORN9]nociceptin(1‐13)NH2able to affect brain antioxidant status in control and kainic acid‐treated rats?

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Resources

About

Are nociceptin(1‐13)NH₂and its structural analogue [ORN⁹]nociceptin(1‐13)NH₂able to affect brain antioxidant status in control and kainic acid‐treated rats?