The effect of ganglioside GQ1b on the NMDA receptor signaling pathway in H19-7 cells and rat hippocampus.
Gangliosides, sialic acid-containing glycosphingolipids, are related to various synaptic functions in the rat brain. Previously, we investigated the behavioral effects of the ganglioside GQ1b on learning and memory using the Y-maze and Morris water maze test. GQ1b-treated rats showed highly increased memory performance on the Y-maze and the Morris water maze test. In this study, we determined the role of GQ1b on the activation of the N-methyl-d-aspartate (NMDA) receptor signaling pathway in H19-7 rat hippocampal cells and the hippocampus of rats. After 12 h of treatment with GQ1b, the expression levels of NMDA receptor subunit 2A and 2B were increased in H19-7 cells and the hippocampus of rats. In addition, treatment of GQ1b increased the tyrosine phosphorylation of NR2B that may enhance NMDA receptor synaptic activation and enhancement of NMDA receptors. Also, following GQ1b treatment, the phosphorylation of extracellular signal-regulated kinases (ERK1/2) and protein kinase A, a cAMP activated protein kinase (PKA) increased in H19-7 cells and the hippocampus of rats. These increases resulted in an increase in the phosphorylation of cAMP response element binding protein (CREB). These results suggest that GQ1b might facilitate the activation of the NMDA receptor signaling pathway in the hippocampus of rats, an effect which is dependent on ERK1/2, PKA and CREB phosphorylation. Also, these data support our previous result that GQ1b improves the learning and memory of rats.
Jung
W R
WR
Department of Biological Science, Sungkyunkwan University, Jangan-Gu, Suwon, Gyeonggi-Do, Republic of Korea.
Kim
H G
HG
Shin
M K
MK
Park
D I
DI
Kim
K L
KL
D000818:Animals; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005732:Gangliosides / Q000494:pharmacology / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000502:physiology*; D015398:Signal Transduction
D017362:Cyclic AMP Response Element-Binding Protein; D017868:Cyclic AMP-Dependent Protein Kinases; D005732:Gangliosides; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D016194:Receptors, N-Methyl-D-Aspartate; C121001:NR2B NMDA receptor; C039129:GQ1b ganglioside