title: The ganglioside GQ1b regulates BDNF expression via the NMDA receptor signaling pathway.
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.
authors.affiliation: Department of Biological Science, Sungkyunkwan University, Suwon, Gyeonggi-Do 440-746, Republic of Korea. Electronic address: smk9444778@skku.edu.
authors.forename: Min Kyoo
authors.initials: MK
authors.lastname: Shin
authors.affiliation: Department of Biological Science, Sungkyunkwan University, Suwon, Gyeonggi-Do 440-746, Republic of Korea. Electronic address: skumac@skku.edu.
authors.forename: Woo Ram
authors.initials: WR
authors.lastname: Jung
authors.affiliation: Department of Biological Science, Sungkyunkwan University, Suwon, Gyeonggi-Do 440-746, Republic of Korea. Electronic address: tenork100@kipo.go.kr.
authors.forename: Hong Gi
authors.initials: HG
authors.lastname: Kim
authors.affiliation: Department of Physiology, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: doinfine39@gmail.com.
authors.forename: Seung Eon
authors.initials: SE
authors.lastname: Roh
authors.affiliation: Department of Biological Science, Sungkyunkwan University, Suwon, Gyeonggi-Do 440-746, Republic of Korea. Electronic address: hahaaaa@hanmail.net.
authors.forename: Choong Hwan
authors.initials: CH
authors.lastname: Kwak
authors.affiliation: Department of Biological Science, Sungkyunkwan University, Suwon, Gyeonggi-Do 440-746, Republic of Korea. Electronic address: chkimbio@skku.edu.
authors.forename: Cheorl Ho
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Physiology, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: sangjkim@snu.ac.kr.
authors.forename: Sang Jeong
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Biological Science, Sungkyunkwan University, Suwon, Gyeonggi-Do 440-746, Republic of Korea. Electronic address: kimkl@skku.edu.
authors.forename: Kil Lyong
authors.initials: KL
authors.lastname: Kim
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005732:Gangliosides / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D005732:Gangliosides; D016194:Receptors, N-Methyl-D-Aspartate; C039129:GQ1b ganglioside
keywords: BDNF; Brain-derived neurotrophic factor; CREB; D-2-amino-5-phosphonopentanoate; D-AP5; D-PDMP; D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propranol; ERK; GQ1b; Ganglioside; LTP; Long term potentiation; N-methyl-d-aspartate; N-methyl-d-aspartate receptor; NMDA; cAMP response element binding protein; extracellular signal-regulated kinase