The ganglioside GQ1b regulates BDNF expression via the NMDA receptor signaling pathway

Min Kyoo Shin, Woo Ram Jung, Hong Gi Kim, Seung Eon Roh, Choong Hwan Kwak, Cheorl Ho Kim, Sangjeong Kim, Kil Lyong Kim

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11 Citations (Scopus)

Abstract

Gangliosides are sialic acid-containing glycosphingolipids which play a role in neuronal functions. Among the gangliosides, tetrasialoganglioside GQ1b shows neurotrophic factor-like actions, such as increasing neurite outgrowth, cell proliferation, and long-term potentiation. In addition, we recently reported that GQ1b improves spatial learning and memory performance in naïve rats. However, it is still unknown how GQ1b exerts its diverse neuronal functions. Thus, we hypothesized that GQ1b might influence synaptic activity by regulating brain-derived neurotrophic factor (BDNF) expression, which is an important protein for synaptic plasticity and cognition. Interestingly, GQ1b treatment increased BDNF expression in GQ1b-null SH-SY5Y cell lines and rat primary cortical neurons. Additionally, we confirmed whether the observed effects were due to GQ1b or due to a ganglioside with fewer sialic acid molecules (GT1b and GD1b) created by the sialidases present on the plasma membranes, by directly applying GT1b and GD1b or GQ1b co-treated with a sialidase inhibitor. Treatment with GT1b or GD1b had no effect on BDNF expression, whereas co-treatment with a sialidase inhibitor and GQ1b significantly increased BDNF levels. Moreover, GQ1b restored the decreased BDNF expression induced by the ganglioside synthesis inhibitor, D-PDMP, in rat primary cortical neurons. GQ1b treatment significantly increased BDNF levels, whereas pretreatment with the N-methyl-d-aspartate (NMDA) receptor antagonist D-AP5 blocked the effects of GQ1b on BDNF expression, suggesting that GQ1b regulates BDNF expression via the NMDA receptor signaling. Finally, we performed an intracerebroventricular GQ1b injection, which resulted in increased prefrontal and hippocampal BDNF expression in vivo. These findings demonstrate, for the first time, that tetrasialoganglioside GQ1b regulates BDNF expression in vitro and in vivo.

Original languageEnglish
Pages (from-to)414-421
Number of pages8
JournalNeuropharmacology
Volume77
DOIs
StatePublished - 1 Jan 2014

Fingerprint

Brain-Derived Neurotrophic Factor
Gangliosides
Neuraminidase
N-Acetylneuraminic Acid
aspartic acid receptor
GQ1b ganglioside
Neurons
Glycosphingolipids
Neuronal Plasticity
Long-Term Potentiation
Nerve Growth Factors
Therapeutics
Cognition
Cell Proliferation
Cell Membrane
Cell Line
Injections

Keywords

  • Brain-derived neurotrophic factor
  • GQ1b
  • Ganglioside
  • N-methyl-d-aspartate receptor

Cite this

Shin, M. K., Jung, W. R., Kim, H. G., Roh, S. E., Kwak, C. H., Kim, C. H., ... Kim, K. L. (2014). The ganglioside GQ1b regulates BDNF expression via the NMDA receptor signaling pathway. Neuropharmacology, 77, 414-421. https://doi.org/10.1016/j.neuropharm.2013.10.022
Shin, Min Kyoo ; Jung, Woo Ram ; Kim, Hong Gi ; Roh, Seung Eon ; Kwak, Choong Hwan ; Kim, Cheorl Ho ; Kim, Sangjeong ; Kim, Kil Lyong. / The ganglioside GQ1b regulates BDNF expression via the NMDA receptor signaling pathway. In: Neuropharmacology. 2014 ; Vol. 77. pp. 414-421.
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The ganglioside GQ1b regulates BDNF expression via the NMDA receptor signaling pathway. / Shin, Min Kyoo; Jung, Woo Ram; Kim, Hong Gi; Roh, Seung Eon; Kwak, Choong Hwan; Kim, Cheorl Ho; Kim, Sangjeong; Kim, Kil Lyong.

In: Neuropharmacology, Vol. 77, 01.01.2014, p. 414-421.

Research output: Contribution to journalArticleResearchpeer-review

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