Disialogangliosides induce neurodegeneration in rat mesencephalic cultures

Chung, Eun‐Sung; Jin, Byung Kwan

doi:10.1016/j.bbrc.2006.05.150

Cited by 3 publications

(5 citation statements)

References 24 publications

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“…Many studies also demonstrate that, GD3 disrupts mitochondria membrane potential [32,33], induces cell death and activates caspases in HuT78, derived from a human cutaneous T cell lymphoma [34]. Similarly, neurotoxicity of major brain gangliosides, such as GD1a and GD1b against dopaminergic neurons in mesencephalic cultures has been reported [35]. We also found that GT1b was neurotoxic to mesencephalic dopaminergic neurons in vivo and in vitro [23,24].…”

Section: Discussionsupporting

confidence: 58%

“…As described previously, the cell composition included ~5% astrocytes and less than 1% microglia which were glial fibrillary acidic protein (GFAP; Sigma) immunopositive (ip) and CD11b (OX-42, Serotec, Oxford, UK)-ip cells, respectively. The remaining cells were presumed to be neurons, 4.5~6% and 9.5~11% of which were tyrosine hydroxylase-ip (TH-ip) and gamma amino butyric acid (GABA, ; Sigma)-ip neurons, respectively [35]. …”

Section: Methodsmentioning

confidence: 99%

“…As previously described [24,35], paraformaldehyde-fixed cells were immunostained with following cell type specific antibodies; mouse-neuron specific nuclear protein (NeuN, 1:300) for general neurons, mouse-TH (1:7500) for DA neurons or rabbit-GABA (1:2000) for GABAergic neurons. Cultures were incubated with a primary antibody for overnight at room temperature (RT) and subsequently incubated with an appropriated biotinylated secondary antibody.…”

Section: Methodsmentioning

confidence: 99%

“…The measurement of dopamine uptake was performed as our described previously [24,35]. Briefly, cultures were washed twice with the incubation solution (HBSS containing 10 mM HEPES, 0.6% glucose, 0.2 mM pargyline, and 0.01% ascorbic acid, pH 7.4), and then incubated at 37°C for 20 min in incubation solution with a final concentration of 83.3 nM tritiated dopamine ([ 3 H]dopamine, 444 GBq/mmol).…”

Section: Methodsmentioning

confidence: 99%

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GT1b-induced neurotoxicity is mediated by the Akt/GSK-3/tau signaling pathway but not caspase-3 in mesencephalic dopaminergic neurons

et al. 2010

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BackgroundGangliosides, sialic acid-containing glycosphingolipids exist in mammalian cell membranes particularly neuronal membranes. The trisialoganglioside (GT1b) is one of the major brain gangliosides and acts as an endogenous regulator in the brain. We previously showed GT1b induces mesencephalic dopaminergic (DA) neuronal death, both in vivo and in vitro. We further investigate the underlying mechanisms of GT1b neurotoxicity.ResultsConsistent with earlier findings, GT1b attenuated the DA neuron number and dopamine uptake level in mesencephalic cultures. Morphological evidence revealed GT1b-induced chromatin condensation and nuclear fragmentation as well as an increased number of TUNEL-positive cells, compared to control cultures. Interestingly, while GT1b enhanced caspase-3 activity, DEVD, a caspase-3 inhibitor, failed to rescue DA neuronal death. Immunoblot analysis revealed that GT1b inactivates Akt through dephosphorylation at both Ser473 and Thr308, subsequent dephosphorylation of GSK-3β, a substrate of Akt, and hyperphosphorylation of tau, downstream of GSK-3β. Moreover, a GSK-3β specific inhibitor, L803-mt, attenuated tau phosphorylation and rescued DA neurons from cell death in mesencephalic cultures.ConclusionOur data provide novel evidence that a Akt/GSK-3β/tau-dependent, but not caspase-3 signaling pathway plays a pivotal role in GT1b-mediated neurotoxic actions on mesencephalic DA neurons.

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Section: Discussionsupporting

confidence: 58%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

GT1b-induced neurotoxicity is mediated by the Akt/GSK-3/tau signaling pathway but not caspase-3 in mesencephalic dopaminergic neurons

et al. 2010

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“…When cultures were immunostained with cell-type specific Abs (see above immunohistochemistry), the cell composition included ∼5% astrocytes and less than ∼1% microglia (21). The remaining cells were presumed to be neurons, 1-1.2 and 9.5-11% of which were TH-ip and g amino butyric acid-ip neurons, respectively (22). For methyl green staining, cells were stained for 5 min at room temperature with 0.5% methyl green solution (Sigma-Aldrich) after immunostained with TH Ab.…”

Section: Neuron-enriched Mesencephalic Culturesmentioning

confidence: 99%

Ethyl Pyruvate Rescues Nigrostriatal Dopaminergic Neurons by Regulating Glial Activation in a Mouse Model of Parkinson’s Disease

Huh

Chung

Piao

et al. 2011

The Journal of Immunology

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This study examined whether ethyl pyruvate (EP) promotes the survival of nigrostriatal dopaminergic (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease. MPTP induced degeneration of nigrostriatal DA neurons and glial activation as visualized by tyrosine hydroxylase, macrophage Ag complex-1, and/or glial fibrillary acidic protein immunoreactivity. Western blotting and immunohistochemistry showed activation of microglial NADPH oxidase and astroglial myeloperoxidase (MPO) and subsequent reactive oxygen species/reactive nitrogen species production and oxidative DNA damage in the MPTP-treated substantia nigra. Treatment with EP prevented degeneration of nigrostriatal DA neurons, increased striatal dopamine levels, and improved motor function. This neuroprotection afforded by EP was associated with the suppression of astroglial MPO expression, NADPH oxidase-, and/or inducible NO synthase-derived reactive oxygen species/reactive nitrogen species production by activated microglia. Interestingly, EP was found to protect DA neurons from 1-methyl-4-phenyl-pyridinium neurotoxicity in cocultures of mesencephalic neurons and microglia but not in neuron-enriched mesencephalic cultures devoid of microglia. The present findings show that EP may inhibit glial-mediated oxidative stress, suggesting that EP may have therapeutic value in the treatment of aspects of Parkinson’s disease related to glia-derived oxidative damage.

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Transient receptor potential vanilloid subtype 1 contributes to mesencephalic dopaminergic neuronal survival by inhibiting microglia-originated oxidative stress

Park

Kim

Jin

2012

Brain Research Bulletin

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Disialogangliosides induce neurodegeneration in rat mesencephalic cultures

Cited by 3 publications

References 24 publications

GT1b-induced neurotoxicity is mediated by the Akt/GSK-3/tau signaling pathway but not caspase-3 in mesencephalic dopaminergic neurons

GT1b-induced neurotoxicity is mediated by the Akt/GSK-3/tau signaling pathway but not caspase-3 in mesencephalic dopaminergic neurons

Ethyl Pyruvate Rescues Nigrostriatal Dopaminergic Neurons by Regulating Glial Activation in a Mouse Model of Parkinson’s Disease

Transient receptor potential vanilloid subtype 1 contributes to mesencephalic dopaminergic neuronal survival by inhibiting microglia-originated oxidative stress

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