PMID- 24184316 OWN - NLM STAT- MEDLINE DCOM- 20140826 LR - 20131216 IS - 1873-7064 (Electronic) IS - 0028-3908 (Linking) VI - 77 DP - 2014 Feb TI - The ganglioside GQ1b regulates BDNF expression via the NMDA receptor signaling pathway. PG - 414-21 LID - S0028-3908(13)00498-X [pii] LID - 10.1016/j.neuropharm.2013.10.022 [doi] AB - 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 naive 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. CI - Copyright (c) 2013 Elsevier Ltd. All rights reserved. FAU - Shin, Min Kyoo AU - Shin MK AD - Department of Biological Science, Sungkyunkwan University, Suwon, Gyeonggi-Do 440-746, Republic of Korea. Electronic address: smk9444778@skku.edu. FAU - Jung, Woo Ram AU - Jung WR AD - Department of Biological Science, Sungkyunkwan University, Suwon, Gyeonggi-Do 440-746, Republic of Korea. Electronic address: skumac@skku.edu. FAU - Kim, Hong Gi AU - Kim HG AD - Department of Biological Science, Sungkyunkwan University, Suwon, Gyeonggi-Do 440-746, Republic of Korea. Electronic address: tenork100@kipo.go.kr. FAU - Roh, Seung Eon AU - Roh SE AD - Department of Physiology, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: doinfine39@gmail.com. FAU - Kwak, Choong Hwan AU - Kwak CH AD - Department of Biological Science, Sungkyunkwan University, Suwon, Gyeonggi-Do 440-746, Republic of Korea. Electronic address: hahaaaa@hanmail.net. FAU - Kim, Cheorl Ho AU - Kim CH AD - Department of Biological Science, Sungkyunkwan University, Suwon, Gyeonggi-Do 440-746, Republic of Korea. Electronic address: chkimbio@skku.edu. FAU - Kim, Sang Jeong AU - Kim SJ AD - Department of Physiology, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: sangjkim@snu.ac.kr. FAU - Kim, Kil Lyong AU - Kim KL AD - Department of Biological Science, Sungkyunkwan University, Suwon, Gyeonggi-Do 440-746, Republic of Korea. Electronic address: kimkl@skku.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131030 PL - England TA - Neuropharmacology JT - Neuropharmacology JID - 0236217 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Gangliosides) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 68652-37-9 (GQ1b ganglioside) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Cell Line, Tumor MH - Cells, Cultured MH - Cerebral Cortex/cytology/drug effects/metabolism MH - Gangliosides/*pharmacology MH - Humans MH - Mice MH - Neurons/cytology/drug effects/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, N-Methyl-D-Aspartate/*metabolism MH - Signal Transduction/drug effects/*physiology OTO - NOTNLM OT - BDNF OT - Brain-derived neurotrophic factor OT - CREB OT - D-2-amino-5-phosphonopentanoate OT - D-AP5 OT - D-PDMP OT - D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propranol OT - ERK OT - GQ1b OT - Ganglioside OT - LTP OT - Long term potentiation OT - N-methyl-d-aspartate OT - N-methyl-d-aspartate receptor OT - NMDA OT - cAMP response element binding protein OT - extracellular signal-regulated kinase EDAT- 2013/11/05 06:00 MHDA- 2014/08/27 06:00 CRDT- 2013/11/05 06:00 PHST- 2013/05/24 00:00 [received] PHST- 2013/09/17 00:00 [revised] PHST- 2013/10/18 00:00 [accepted] PHST- 2013/11/05 06:00 [entrez] PHST- 2013/11/05 06:00 [pubmed] PHST- 2014/08/27 06:00 [medline] AID - S0028-3908(13)00498-X [pii] AID - 10.1016/j.neuropharm.2013.10.022 [doi] PST - ppublish SO - Neuropharmacology. 2014 Feb;77:414-21. doi: 10.1016/j.neuropharm.2013.10.022. Epub 2013 Oct 30.