title: Impaired hippocampal long-term potentiation and failure of learning in β1,4-N-acetylgalactosaminyltransferase gene transgenic mice.
abstract: Gangliosides (sialic acid-containing glycosphingolipids) play important roles in many physiological functions, including synaptic plasticity in the hippocampus, which is considered as a cellular mechanism of learning and memory. In the present study, three types of synaptic plasticity, long-term potentiation (LTP), long-term depression (LTD) and reversal of LTP (depotentiation, DP), in the field excitatory post-synaptic potential in CA1 hippocampal neurons and learning behavior were examined in β1,4-N-acetylgalactosaminyltransferase (β1,4 GalNAc-T; GM2/GD2 synthase) gene transgenic (TG) mice, which showed a marked decrease in b-pathway gangliosides (GQ1b, GT1b and GD1b) in the brain and isolated hippocampus compared with wild-type (WT) mice. The magnitude of the LTP induced by tetanus (100 pulses at 100 Hz) in TG mice was significantly smaller than that in control WT mice, whereas there was no difference in the magnitude of the LTD induced by three short trains of low-frequency stimulation (LFS) (200 pulses at 1 Hz) at 20 min intervals between the two groups of mice. The reduction in the LTP produced by delivering three trains of LFS (200 pulses at 1 Hz, 20 min intervals) was significantly greater in the TG mice than in the WT mice. Learning was impaired in the four-pellet taking test (4PTT) in TG mice, with no significant difference in daily activity or activity during the 4PTT between TG and WT mice. These results suggest that the overexpression of β1,4 GalNAc-T resulted in altered synaptic plasticity of LTP and DP in hippocampal CA1 neurons and learning in the 4PTT, and this is attributable to the shift from b-pathway gangliosides to a-pathway gangliosides.
authors: Department of Physiology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
authors: Kotaro
authors: K
authors: Ikarashi
authors: Hiroki
authors: H
authors: Fujiwara
authors: Yoshihiko
authors: Y
authors: Yamazaki
authors: Jun-Ichi
authors: J
authors: Goto
authors: Kenya
authors: K
authors: Kaneko
authors: Hiroshi
authors: H
authors: Kato
authors: Satoshi
authors: S
authors: Fujii
authors: Hiroshi
authors: H
authors: Sasaki
authors: Satoshi
authors: S
authors: Fukumoto
authors: Keiko
authors: K
authors: Furukawa
authors: Hatsue
authors: H
authors: Waki
authors: Koichi
authors: K
authors: Furukawa
mesh_terms: D000818:Animals; D005732:Gangliosides / Q000378:metabolism; D006624:Hippocampus / Q000502:physiology*; D007858:Learning; D017774:Long-Term Potentiation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics* / Q000378:metabolism
chemical_list: D005732:Gangliosides; D017350:N-Acetylgalactosaminyltransferases; C023220:(N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase