Antagonism of NMDA receptors by σ receptor ligands attenuates chemical ischemia-induced neuronal death in vitro

Kume, Toshiaki; Nishikawa, Hiroyuki; Taguchi, Ryota; Hashino, Asami; Katsuki, Hiroshi; Kaneko, Shuji; Minami, Masabumi; Satoh, Masamichi; Akaike, Akinori

doi:10.1016/s0014-2999(02)02582-7

Cited by 55 publications

(44 citation statements)

References 39 publications

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“…Only mature cultures (12 -14 days in vitro) were used for experiments. Immunochemical staining with anti-microtubule associated protein-2 (MAP-2) antibody and anti-glial fibrillary acidic protein (GFAP) antibody revealed that the culture method used in this study provided cell cultures containing about 90% neurons as described previously (23).…”

Section: +mentioning

confidence: 79%

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Schizandrin Protects Primary Cultures of Rat Cortical Cells From Glutamate-Induced Excitotoxicity

Cheng

Hsieh

et al. 2008

J Pharmacol Sci

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Abstract. The neuroprotective effect of schizandrin on the glutamate (Glu)-induced neuronal excitotoxicity and its potential mechanisms were investigated using primary cultures of rat cortical cells. After exposure of primary cultures of rat cortical cells to 10 μM Glu for 24 h, cortical cell cultures exhibited remarkable apoptotic death. Pretreatment of the cortical cell cultures with schizandrin (10, 100 μM) for 2 h significantly protected cortical neurons against Glu-induced excitotoxicity. The neuroprotective activity of schizandrin was the most potent at the concentration of 100 μΜ. Schizandrin reduced apoptotic characteristics by DAPI staining in Glu-injured cortical cell cultures. In addition, schizandrin diminished the intracellular Ca 2+ influx, inhibited the subsequent overproduction of nitric oxide (NO), reactive oxygen species (ROS), and cytochrome c, and preserved the mitochondrial membrane potential. Furthermore, schizandrin also increased the cellular level of glutathione (GSH) and inhibited the membrane lipid peroxidation malondialdehyde (MDA). As indicated by Western blotting, schizandrin attenuated the protein level changes of procaspase-9, caspase-9, and caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP). Taken together, these results suggest that schizandrin protected primary cultures of rat cortical cells against Glu-induced apoptosis through a mitochondria-mediated pathway and oxidative stress.

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Section: +mentioning

confidence: 79%

“…Primary neuronal cultures of cerebral cortex were obtained from rat embryos (E16-18) according to Nishikawa (22) with modifications as described before (23). The cerebral cortex of rat embryos were dissected and placed in cold HBSS.…”

Section: Primary Cultures Of Rat Cortical Cellmentioning

confidence: 99%

Schizandrin Protects Primary Cultures of Rat Cortical Cells From Glutamate-Induced Excitotoxicity

Cheng

Hsieh

et al. 2008

J Pharmacol Sci

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“…It has been reported that σ receptor ligands may have bidirectional modulation on NMDA receptor function, depending on ligand structure and the ligand concentrations that are used. This modulation of NMDA receptor function might occur directly or via an interaction with σ1 receptors (Nishikawa et al, 2000;Kume et al, 2002;Martina et al, 2007). To examine whether an indirect or a direct modulation of NMDA receptors might contribute to our observed in vivo effects of LS-1-137 on cognitive function presented here or the neuroprotective effects we reported previously (Luedtke et al, 2012), we assessed the effect of LS-1-137 on NMDA responses recorded from HEK 293 cells transiently expressing rat recombinant GluN1NR2A receptors.…”

Section: Effect Of Ls-1-137 On Recombinant Nmda Receptorsmentioning

confidence: 95%

The effects of sigma (σ1) receptor‐selective ligands on muscarinic receptor antagonist‐induced cognitive deficits in mice

Malik

Rangel‐Barajas

Sumien

et al. 2015

British J Pharmacology

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BACKGROUND AND PURPOSECognitive deficits in patients with Alzheimer's disease, Parkinson's disease, traumatic brain injury and stroke often involve alterations in cholinergic signalling. Currently available therapeutic drugs provide only symptomatic relief. Therefore, novel therapeutic strategies are needed to retard and/or arrest the progressive loss of memory. EXPERIMENTAL APPROACHScopolamine-induced memory impairment provides a rapid and reversible phenotypic screening paradigm for cognition enhancement drug discovery. Male C57BL/6J mice given scopolamine (1 mg·kg −1 ) were used to evaluate the ability of LS-1-137, a novel sigma (σ1) receptor-selective agonist, to improve the cognitive deficits associated with muscarinic antagonist administration. KEY RESULTSLS-1-137 is a high-affinity (Ki = 3.2 nM) σ1 receptor agonist that is 80-fold selective for σ1, compared with σ2 receptors. LS-1-137 binds with low affinity at D2-like (D2, D3 and D4) dopamine and muscarinic receptors. LS-1-137 was found to partially reverse the learning deficits associated with scopolamine administration using a water maze test and an active avoidance task. LS-1-137 treatment was also found to trigger the release of brain-derived neurotrophic factor from rat astrocytes. CONCLUSIONS AND IMPLICATIONSThe σ1 receptor-selective compound LS-1-137 may represent a novel candidate cognitive enhancer for the treatment of muscarinic receptor-dependent cognitive deficits. AbbreviationsAD, Alzheimer's disease; BDNF, brain-derived neurotrophic factor; BiP, binding immunoglobulin protein; ER, endoplasmic reticulum; PPCC, methyl(1R,2S/1S,2R)-2-[4-hydroxy-4-phenylpiperidin-1-yl)methyl]-1-(4-methylphenyl)cyclopro-panecarboxylate; QNB, quinuclidinyl benzylate IntroductionImpairment in learning and memory is seen in (i) aged populations, (ii) patients with neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease, (iii) stroke patients and (iv) patients with traumatic brain injury (Scarpini et al., 2003;Tarawneh and Galvin, 2010;Ruscher et al., 2011). Although the causes of cognitive impairments vary, previous studies have suggested that alteration in cholinergic neurotransmission may play an important role in the disruption of learning and memory (Francis et al., 1999;Craig et al., 2011;Dumas and Newhouse, 2011). According to the cholinergic hypothesis, age-dependent cognitive decline is primarily related to impairment in cholinergic neurotransmission (Bartus et al., 1982;Coyle et al., 1983;Kirk et al., 1994). Administration of the competitive cholinergic muscarinic receptor antagonist scopolamine causes cognitive dysfunctions similar to those observed in normal aging and AD (Ebert and Kirch, 1998;Bejar et al., 1999;Klinkenberg and Blokland, 2010). A scopolamine-dependent model of cognitive deficits has been used to screen for potential cognition-enhancing drugs (Flood and Cherkin, 1986;Ennaceur and Meliani, 1992;Antonini et al., 2009;Klinkenberg and Blokland, 2010). Since the sigma σ1 receptor is known to potently modulate cho...

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“…Neurons and glial cells for a co-culture system were obtained from the cerebral cortex of fetal Wistar rats (17 -19 days of gestation) according to the procedures described previously (26,27). Briefly, whole cerebral cortex was isolated from a fetal rat brain and was minced using scalpel blades, and filtered through stainless steel mesh (150 mesh).…”

Section: Co-culture Of Primary Neurons and Glia Isolated From Fetal Rmentioning

confidence: 99%

Nicotine- and Tar-Free Cigarette Smoke Induces Cell Damage Through Reactive Oxygen Species Newly Generated by PKC-Dependent Activation of NADPH Oxidase

et al. 2012

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Abstract.We examined cytotoxic effects of nicotine/tar-free cigarette smoke extract (CSE) on C6 glioma cells. The CSE induced plasma membrane damage (determined by lactate dehydrogenase leakage and propidium iodide uptake) and cell apoptosis {determined by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] reduction activity and DNA fragmentation}. The cytotoxic activity decayed with a half-life of approximately 2 h at 37°C, and it was abolished by N-acetyl-L-cysteine and reduced glutathione. The membrane damage was prevented by catalase and edaravone (a scavenger of• OH) but not by superoxide dismutase, indicating involvement of • OH. In contrast, the CSE-induced cell apoptosis was resistant to edaravone and induced by authentic H 2 O 2 or O 2 − generated by the xanthine/xanthine oxidase system, indicating involvement of H 2 O 2 or O 2 − in cell apoptosis. Diphenyleneiodonium [NADPH oxidase (NOX) inhibitor] and bisindolylmaleimide I [BIS I, protein kinase C (PKC) inhibitor] abolished membrane damage, whereas they partially inhibited apoptosis. These results demonstrate that 1) a stable component(s) in the CSE activates PKC, which stimulates NOX to generate reactive oxygen species (ROS), causing membrane damage and apoptosis; 2) different ROS are responsible for membrane damage and apoptosis; and 3) part of the apoptosis is caused by oxidants independently of PKC and NOX.[Supplementary methods and Figure: available only at http://dx

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Antagonism of NMDA receptors by σ receptor ligands attenuates chemical ischemia-induced neuronal death in vitro

Cited by 55 publications

References 39 publications

Schizandrin Protects Primary Cultures of Rat Cortical Cells From Glutamate-Induced Excitotoxicity

Schizandrin Protects Primary Cultures of Rat Cortical Cells From Glutamate-Induced Excitotoxicity

The effects of sigma (σ1) receptor‐selective ligands on muscarinic receptor antagonist‐induced cognitive deficits in mice

Nicotine- and Tar-Free Cigarette Smoke Induces Cell Damage Through Reactive Oxygen Species Newly Generated by PKC-Dependent Activation of NADPH Oxidase

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