Mechanism of glutamate-induced neurotoxicity in HT22 mouse hippocampal cells

Fukui, Masayuki; Song, Ji-Hoon; Choi, Jin-Sung; Choi, Hye Joung; Zhu, Bao Ting

doi:10.1016/j.ejphar.2009.06.059

Cited by 194 publications

(179 citation statements)

References 21 publications

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“…Our observation suggested that Bax, Bcl-2 and caspase-3 expressions were associated with MSG treatment. Our results were different from Fukui et al (Fukui et al, 2009) study which showed that glutamate induced-apoptosis was independent of Bax, Bcl-2 and caspases. Such discrepancy may be due to the experimental system used, we studied invivo zebrafish observing the whole brain, whereas Fukui et al (Fukui et al, 2009) used in vitro hippocampal cells.…”

Section: Msg Increased Circle Swimming Events and Decreased Locomotorcontrasting

confidence: 56%

“…Our results were different from Fukui et al (Fukui et al, 2009) study which showed that glutamate induced-apoptosis was independent of Bax, Bcl-2 and caspases. Such discrepancy may be due to the experimental system used, we studied invivo zebrafish observing the whole brain, whereas Fukui et al (Fukui et al, 2009) used in vitro hippocampal cells. Another mechanism to recover from apoptosis due to excessive glutamate toxicity is that zebrafish may regenerate cells to replace the affected brain cells.…”

Section: Msg Increased Circle Swimming Events and Decreased Locomotorcontrasting

confidence: 56%

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Monosodium Glutamate Exposure at Early Developmental Stage Increases Apoptosis and Stereotypic Behavior Risks on Zebrafish (Danio Rerio) Larvae

Kurnianingsih

2016

Indonesian J. Pharm.

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Excessive glutamate may give neurotoxic effects and contribute to Autism spectrum disorder(ASD). In this study, we investigated prolonged exposure effects of 10 µg/mL Monosodium Glutamate (MSG) on intracellular calcium level, bax, bcl-2, ratio of bax/bcl-2 genes expression, caspase-3, apoptosis of brain cells and stereotypic behavior of Zebrafish (Danio rerio) larvae at early developmental stages. Genes expression were determined by real time PCR, caspase-3 using ELISA, intracellular Ca 2+ and apoptotic cells of brain using confocal microscopy, locomotor activity by using crossing lines assay whereas stereotypic behavior by circle swimming. The results indicated that MSG exposure increased brain bax and bcl-2; and caspase-3; intracellular Ca 2+ ; and apoptosis; stereotypic behavior; and decreased locomotor activity. Termination of MSG treatments resulted in recovery of bax, bcl-2, caspase-3 basal levels and stereotypic behavior. In conclusion, MSG exposure at early embryonic stage increased brain cell damage and risk of behavior changes.

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Section: Msg Increased Circle Swimming Events and Decreased Locomotorcontrasting

confidence: 56%

Section: Msg Increased Circle Swimming Events and Decreased Locomotorcontrasting

confidence: 56%

Monosodium Glutamate Exposure at Early Developmental Stage Increases Apoptosis and Stereotypic Behavior Risks on Zebrafish (Danio Rerio) Larvae

Kurnianingsih

2016

Indonesian J. Pharm.

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“…Oxidative stress in central nervous system (CNS) can lead to cell death and necrosis and contributes to various neurodegenerative disorders including AD, Parkinson’s disease and Huntington’s disease (Coyle and Puttfarcken, 1993; Satoh et al ., 1998). Glutamate is an endogenous excitatory neurotransmitter and high concentration of glutamate induced the cell death due to oxidative stress (Choi, 1988; Fukui et al ., 2009). Glutamate excitotoxicity results in calcium ion (Ca 2+ ) influx, mitochondrial dysfunction, and elevation of ROS level and depletion of antioxidant defense system including glutathione (GSH) and glutathione reductase (GR) by inhibition of cystine uptake (Choi, 1985; Murphy et al ., 1989; Tan et al ., 1998a).…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effect of Steamed and Fermented Codonopsis lanceolata

Weon

Yun

Lee

et al. 2014

Biomolecules & Therapeutics

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Codonopsis lanceolata has been used as an herbal medicine for several lung inflammatory diseases, such as asthma, tonsillitis, and pharyngitis. Previously, we showed the neuroprotective effect of steamed and fermented C. lanceolata (SFC) in vitro and in vivo. In the current study, the treatment of HT22 cells with SFC decreased glutamate-induced cell death, suggesting that SFC protected HT22 cells from glutamate-induced cytotoxicity. Based on these, we sought to elucidate the mechanisms of the neuro-protective effect of SFC by measuring the oxidative stress parameters and the expression of Bax and caspase-3 in HT22 cells. SFC reduced contents of ROS, Ca2+ and NO. Moreover, SFC restored contents of glutathione and glutathione reductase as well as inhibited Bax and caspase-3 activity in HT22 cells. These results indicate that steamed and fermented C. lanceolata (SFC) extract protected HT22 cells by anti-oxidative effect and inhibition of the expression of Bax and caspase-3.

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“…These agents were used at concentrations that were previously reported to inhibit toxicity in HT-22 cells. 27,28 Despite the increased sensitivity of HuR lo cells to glutamate, they became fully protected by antioxidants as did HuR hi cells (Figure 3f). Thus, HuR acts to protect neurons from oxidative neurotoxicity.…”

Section: Elavl1mentioning

confidence: 99%

Neuroprotection requires the functions of the RNA-binding protein HuR

et al. 2014

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Alterations in the functions of neuronal RNA-binding proteins (RBPs) can contribute to neurodegenerative diseases. However, neurons also express a set of widely distributed RBPs that may have developed specialized functions. Here, we show that the ubiquitous member of the otherwise neuronal Elavl/Hu family of RNA-binding proteins, Elavl1/HuR, has a neuroprotective role. Mice engineered to lack exclusively HuR in the hippocampal neurons of the central nervous system (CNS), maintain physiologic levels of neuronal Elavls and develop a partially diminished seizure response following strong glutamatergic excitation; however, they display an exacerbated neurodegenerative response subsequent to the initial excitotoxic event. This response was phenocopied in hippocampal cells devoid of ionotropic glutamate receptors in which the loss of HuR results in enhanced mitochondrial dysfunction, oxidative damage and programmed necrosis solely after glutamate challenge. The molecular dissection of HuR and nElavl mRNA targets revealed the existence of a HuR-restricted posttranscriptional regulon that failed in HuR-deficient neurons and is involved in cellular energetics and oxidation defense. Thus, HuR acts as a specialized controller of oxidative metabolism in neurons to confer protection from neurodegeneration.

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Mechanism of glutamate-induced neurotoxicity in HT22 mouse hippocampal cells

Cited by 194 publications

References 21 publications

Monosodium Glutamate Exposure at Early Developmental Stage Increases Apoptosis and Stereotypic Behavior Risks on Zebrafish (Danio Rerio) Larvae

Monosodium Glutamate Exposure at Early Developmental Stage Increases Apoptosis and Stereotypic Behavior Risks on Zebrafish (Danio Rerio) Larvae

Neuroprotective Effect of Steamed and Fermented Codonopsis lanceolata

Neuroprotection requires the functions of the RNA-binding protein HuR

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