The effect of X-radiation on cerebellar granule cells grown in culture. Ganglioside GM1 neuroprotective activity

Guelman, Laura Ruth; Zieher, Luis Marı́a; Fiszman, Mónica L.

doi:10.1016/0197-0186(96)00016-2

Cited by 16 publications

(9 citation statements)

References 26 publications

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“…More than the other three major brain gangliosides, GM1 has long been considered to have broad neuroprotective properties [54]–[59]. Exogenously-administered GM1 attenuates lesions induced by, for example, ischemia, X-radiation, glutamate, 6-hydroxydopamine, and ethanol [60]–[63]. A number of neuroprotective mechanisms have been associated with GM1, including increased secretion of neurotrophic factors and activation of TrkB, and inhibition of calcium influx [64], [65].…”

Section: Discussionmentioning

confidence: 99%

Intracranial V. cholerae Sialidase Protects against Excitotoxic Neurodegeneration

Dhanushkodi

McDonald

2011

PLoS ONE

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Converging evidence shows that GD3 ganglioside is a critical effector in a number of apoptotic pathways, and GM1 ganglioside has neuroprotective and noötropic properties. Targeted deletion of GD3 synthase (GD3S) eliminates GD3 and increases GM1 levels. Primary neurons from GD3S−/− mice are resistant to neurotoxicity induced by amyloid-β or hyperhomocysteinemia, and when GD3S is eliminated in the APP/PSEN1 double-transgenic model of Alzheimer's disease the plaque-associated oxidative stress and inflammatory response are absent. To date, no small-molecule inhibitor of GD3S exists. In the present study we used sialidase from Vibrio cholerae (VCS) to produce a brain ganglioside profile that approximates that of GD3S deletion. VCS hydrolyzes GD1a and complex b-series gangliosides to GM1, and the apoptogenic GD3 is degraded. VCS was infused by osmotic minipump into the dorsal third ventricle in mice over a 4-week period. Sensorimotor behaviors, anxiety, and cognition were unaffected in VCS-treated mice. To determine whether VCS was neuroprotective in vivo, we injected kainic acid on the 25th day of infusion to induce status epilepticus. Kainic acid induced a robust lesion of the CA3 hippocampal subfield in aCSF-treated controls. In contrast, all hippocampal regions in VCS-treated mice were largely intact. VCS did not protect against seizures. These results demonstrate that strategic degradation of complex gangliosides and GD3 can be used to achieve neuroprotection without adversely affecting behavior.

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Section: Discussionmentioning

confidence: 99%

Intracranial V. cholerae Sialidase Protects against Excitotoxic Neurodegeneration

Dhanushkodi

McDonald

2011

PLoS ONE

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“…The source–target distance was fixed at 95 cm. A single dose of γ‐rays (0.3 Gy, the dose that produces 50% of cell death (ED 50 ), see Guelman et al, 1996b) was delivered to the dishes, randomly designed as γ‐irradiated, amf /γ‐irradiated and control (sham‐irradiated) groups, 1–2 h after plating. Cell viability was assessed 2 days after irradiation.…”

Section: Methodsmentioning

confidence: 99%

“…After 48 h, viable neurons were counted using Trypan Blue exclusion in five fields of triplicate samples per experimental group (100 mm 2 per dish) using a gridded ocular, under a Nikon inverted phase‐contrast microscope at 200× magnification (Guelman et al, 1996b). For each treatment, 200–300 cells were counted.…”

Section: Methodsmentioning

confidence: 99%

“…In addition, a quantitative assessment of ionizing radiation‐induced damage on rat cerebellum has been recently published (Guelman et al, 2001). Moreover, an in vitro model of radiation‐induced damage on cerebellar immature neurons has been developed, demonstrating a high radiosensitivity (Guelman et al, 1996b).…”

Section: Introductionmentioning

confidence: 99%

“…The aim of the present paper was to test the hypothesis that radiation‐induced damage on immature cerebellar granule cells was mainly mediated by ROS accumulation. The ROS scavenger amf was used in an in vitro model of granule cell cultures, in which sensitivity to low doses of ionizing radiation has been previously reported (Guelman et al, 1996b; Ciani et al, 1996). Moreover, the amf therapeutic effect was investigated by adding the agent at different pre‐ and post‐irradiation intervals, to further provide useful data about the effective “window of opportunity” to reach the best neuroprotection.…”

Section: Introductionmentioning

confidence: 99%

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Ionizing radiation‐induced damage on developing cerebellar granule cells cultures can be prevented by an early amifostine post‐treatment

Guelman

Cabana

Pagotto

et al. 2004

Intl J of Devlp Neuroscience

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Developing central nervous system (CNS) is highly sensitive to ionizing radiation due, in part, to reactive oxygen species (ROS) damage. A variety of compounds able to protect brain cells essentially by decreasing ROS production have been widely used to confirm ROS participation in different mechanisms of brain injury, as well as to evaluate them as therapeutic tools. To test if ionizing radiation-induced damage on immature cerebellar granule cells is mainly mediated by ROS accumulation, a free radical scavenger--amifostine (amf)--was used in an in vitro model. Moreover, the amf therapeutic effect was investigated. Results show that only an early (20-30 min) post-treatment with amf, acting through an antioxidant mechanism, has been effective in preventing cerebellar granule cell loss observed after ionizing radiation exposure in vitro. These data suggest that immature cerebellar granule cells grown in vitro are highly vulnerable to ROS damage and that a therapeutic intervention could be effective in a narrow temporal window. Moreover, radiation-induced cell death can be partially prevented by a complete limitation of ROS generation, suggesting that other mechanisms besides oxidative stress would also be responsible for the cellular damage found in this model.

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Glycosphingolipids and central nervous system–related diseases

Guo

2024

Glycosphingolipids in the Central Nervous System

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The effect of X-radiation on cerebellar granule cells grown in culture. Ganglioside GM1 neuroprotective activity

Cited by 16 publications

References 26 publications

Intracranial V. cholerae Sialidase Protects against Excitotoxic Neurodegeneration

Intracranial V. cholerae Sialidase Protects against Excitotoxic Neurodegeneration

Ionizing radiation‐induced damage on developing cerebellar granule cells cultures can be prevented by an early amifostine post‐treatment

Glycosphingolipids and central nervous system–related diseases

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