Tenuigenin protects cultured hippocampal neurons against methylglyoxal-induced neurotoxicity

Chen, Yujing; Huang, Xiaobo; Li, Zongxin; Yin, Linlin; Chen, Wenqiang; Li, Lin

doi:10.1016/j.ejphar.2010.06.034

Cited by 60 publications

(43 citation statements)

References 32 publications

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“…As our data are focused on the peripheral nervous system, it is important to discuss the MG effect compared to neuroblastoma and central nervous system. At 750 lM MG, the SH-SY5Y human neuroblastoma cells survival rate is reduced to 56.85 ± 1.6% (Li et al 2011), while at only 124 lM MG, the primary rat hippocampal neurons have a drop in viability of 50% (Chen et al 2010). By consequence, one can emphasize that the rate survival of peripheral sensory neurons upon MG treatment is comparable to SH-SY5Y neuroblastoma cells, but is far more increased than for primary rat hippocampal neurons at the same dose.…”

Section: Discussionmentioning

confidence: 82%

Dual Effect of Methylglyoxal on the Intracellular Ca2+ Signaling and Neurite Outgrowth in Mouse Sensory Neurons

et al. 2012

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The formation of advanced glycation end products is one of the major factors involved in diabetic neuropathy, aging, and neurodegenerative diseases. Reactive carbonyl compounds, such as methylglyoxal (MG), play a key role in cross-linking to various proteins in the extracellular matrix, especially in neurons, which have a high rate of oxidative metabolism. The MG effect was tested on dorsal root ganglia primary neurons in cultures from adult male Balb/c mice. Lower MG doses contribute to an increased adherence of neurons on their support and an increased glia proliferation, as proved by MTS assay and bright-field microscopy. Time-lapse fluorescence microscopy by Fura-2 was performed for monitoring the relative fluorescence ratio changes (ΔR/R(0)) upon depolarization and immunofluorescence staining for quantifying the degree of neurites extension. The relative change in fluorescence ratio modifies the amplitude and dispersion depending on the subtype of sensory neurons, the medium-sized neurons are more sensitive to MG treatment when compared to small ones. Low MG concentrations (0-150 μM) increase neuronal viability, excitability, and the capacity of neurite extension, while higher concentrations (250-750 μM) are cytotoxic in a dose-dependent manner. In our opinion, MG could be metabolized by the glyoxalase system inside sensory neurons up to a threshold concentration, afterwards disturbing the cell equilibrium. Our study points out that MG has a dual effect concentration dependent on the neuronal viability, excitability, and neurite outgrowth, but only the excitability changes are soma-sized dependent. In conclusion, our data may partially explain the distinct neuronal modifications in various neurodegenerative pathologies.

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Section: Discussionmentioning

confidence: 82%

Dual Effect of Methylglyoxal on the Intracellular Ca2+ Signaling and Neurite Outgrowth in Mouse Sensory Neurons

et al. 2012

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“…Polygalae Radix, a well-known herb listed in the Chinese Pharmacopoeia (2015 edition), has been prescribed as a tonic, antipsychotic, expectorant and detumescent for thousands of years in traditional Chinese medicine. Modern pharmacological studies have already demonstrated that Polygalae Radix extract exhibits a wide variety of effects, such as hypotensive [7] , anti-inflammatory [8] , anti-depressive [9] , anti-oxidative and antiapoptotic [10] effects, cognitive improvements and cerebral protection [11] . The Polygalae Radix extract BT-11 has been shown to have memory-enhancing effects in rats with scopolamineinduced amnesia [12] and cognition-improving effects in two randomized, double-blind, placebo-controlled comparison studies, one in healthy adults and one in elderly humans [13,14] .…”

Section: Introductionmentioning

confidence: 99%

Polygalasaponin XXXII, a triterpenoid saponin from Polygalae Radix, attenuates scopolamine-induced cognitive impairments in mice

et al. 2016

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Aim: Recent studies show that the extract of a Chinese herb Polygalae Radix exerts cognition-enhancing actions in rats and humans. The aim of this study was to characterize the pharmacological profiles of active compounds extracted from Polygalae Radix. Methods: Two fractions P3 and P6 and two compounds PTM-15 and polygalasaponin XXXII (PGS32) were prepared. Neuroprotective effects were evaluated in primary cortical neurons exposed to high concentration glutamate, serum deficiency or H 2 O 2 . Anti-dementia actions were assessed in scopolamine-induced amnesia in mice using step-through avoidance tests and channel water maze tests. After conducting the channel water maze tests, TrkB phosphorylation in mouse hippocampus was detected using Western blotting. Long-term potentiation (LTP) was induced in the dentate gyrus in adult rats; PGS32 (5 μL 400 μmol/L) was injected into the lateral cerebral ventricle 20 min after high frequency stimulation (HFS). Results: Compared to the fraction P6, the fraction P3 showed more prominent neuroprotective effects in vitro and cognitionenhancing effects in scopolamine-induced amnesia in mice. One active compound PGS32 in the fraction P3 exerted potent cognitionenhancing action: oral administration of PGS32 (0.125 mg· kg -1 ·d -1 ) for 19 days abolished scopolamine-induced memory impairment in mice. Furthermore, PGS32 (0.5 and 2 mg· kg -1 ·d -1 ) significantly stimulated the phosphorylation of TrkB in the hippocampus. Intracerebroventricular injection of PGS32 significantly enhanced HFS-induced LTP in the dentate gyrus of rats. Conclusion: PGS32 attenuates scopolamine-induced cognitive impairments in mice, suggesting that it has a potential for the treatment of cognitive dysfunction and dementia.

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“…which was associated with oxidative stress leading to apoptosis (Kikuchi et al, 1999;Di Loreto et al, 2008;Chen et al, 2010).…”

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confidence: 99%

Role of the Glyoxalase System in Astrocyte-Mediated Neuroprotection

Bélanger

Yang²,

Petit³

et al. 2011

J. Neurosci.

106

131

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The glyoxalase system is the most important pathway for the detoxification of methylglyoxal (MG), a highly reactive dicarbonyl compound mainly formed as a by-product of glycolysis. MG is a major precursor of advanced glycation end products (AGEs), which are associated with several neurodegenerative disorders. Although the neurotoxic effects of MG and AGEs are well characterized, little is known about the glyoxalase system in the brain, in particular with regards to its activity in different neural cell types. Results of the present study reveal that both enzymes composing the glyoxalase system [glyoxalase-1 (Glo-1) and Glo-2] were highly expressed in primary mouse astrocytes compared with neurons, which translated into higher enzymatic activity rates in astrocytes (9.9-and 2.5-fold, respectively). The presence of a highly efficient glyoxalase system in astrocytes was associated with lower accumulation of AGEs compared with neurons (as assessed by Western blotting), a sixfold greater resistance to MG toxicity, and the capacity to protect neurons against MG in a coculture system. In addition, Glo-1 downregulation using RNA interference strategies resulted in a loss of viability in neurons, but not in astrocytes. Finally, stimulation of neuronal glycolysis via lentiviral-mediated overexpression of 6-phosphofructose-2-kinase/fructose-2,6-bisphosphatase-3 resulted in increased MG levels and MG-modified proteins. Since MG is largely produced through glycolysis, this suggests that the poor capacity of neurons to upregulate their glycolytic flux as compared with astrocytes may be related to weaker defense mechanisms against MG toxicity. Accordingly, the neuroenergetic specialization taking place between these two cell types may serve as a protective mechanism against MG-induced neurotoxicity.

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Tenuigenin protects cultured hippocampal neurons against methylglyoxal-induced neurotoxicity

Cited by 60 publications

References 32 publications

Dual Effect of Methylglyoxal on the Intracellular Ca2+ Signaling and Neurite Outgrowth in Mouse Sensory Neurons

Dual Effect of Methylglyoxal on the Intracellular Ca2+ Signaling and Neurite Outgrowth in Mouse Sensory Neurons

Polygalasaponin XXXII, a triterpenoid saponin from Polygalae Radix, attenuates scopolamine-induced cognitive impairments in mice

Role of the Glyoxalase System in Astrocyte-Mediated Neuroprotection

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