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GM1 ganglioside reduces glutamate toxicity to cortical cells

Lowered LDH release and preserved membrane integrity

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Molecular and Chemical Neuropathology

Abstract

As an in vitro model of CNS excitatory amino acid (EAA) injury, rat cortical neuronal cultures were challenged with glutamate (0.5 or 10 mM) and the levels of released lactate dehydrogenase (LDH) were monitored at 1 h, 1, 2, and 7 d. LDH release is correlated with levels of plasma membrane damage. GM1 has been shown to be continuously distributed on the outer surface of CNS cellular membranes. By staining for the distribution of endogenous GM1 ganglioside using cholera toxin/antitoxin immunohistochemistry, we were able to assess morphologically cellular plasma membrane integrity after damage. We used these two measures (LDH and GM1 localization) to study the neuroprotective effects of exogenous GM1 ganglioside to further elucidate its mechanism. Cortical cultures derived from 15-d rat fetuses were subjected to the glutamate challenge for 30 min. Parallel cultures were either pre- or posttreated with 80 μM of GM1. Exposure to 10 mM glutamate caused a highly significant increase in LDH release at 1–48 h. Pretreatment with GM1 reduced the release, whereas post-treatment reduced the LDH release even more. Plasma membrane changes observed by the GM1 immunohistochemistry reflected the LDH release data. All cultures treated with GM1 evidenced substantial structural integrity (continuous staining of GM1 along perykarya and processes) as compared to untreated cultures. These data support our hypothesis that GM1 treatment (pre- and post-) reduces plasma membrane damage.

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Author notes

  1. Sahebarao P. Mahadik

    Present address: Department of Psychiatry, Medical College of Georgia and Veterans Affairs Medical Center, Augusta, GA

Authors and Affiliations

  1. Division of Neuroscience, New York State Psychiatric Institute, Department of Psychiatry, Columbia University, College of Physicians and Surgeons, 10032, New York, NY

    Heljo Laev, Sahebarao P. Mahadik, Jennifer L. Bonheur, Noreen Hernandez & Stephen E. Karpiak

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  1. Heljo Laev
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  2. Sahebarao P. Mahadik
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  3. Jennifer L. Bonheur
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  4. Noreen Hernandez
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Laev, H., Mahadik, S.P., Bonheur, J.L. et al. GM1 ganglioside reduces glutamate toxicity to cortical cells. Molecular and Chemical Neuropathology 20, 229–243 (1993). https://doi.org/10.1007/BF03160076

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