Analysis of gene expression changes associated with long-lasting synaptic enhancement in hippocampal slice cultures after repetitive exposures to glutamate

Katsuhiro Kawaai, Keiko Tominaga-Yoshino, Tomoyoshi Urakubo, Naoko Taniguchi, Yasumitsu Kondoh, Hideo Tashiro, Akihiko Ogura, Tomoko Tashiro

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

We have previously shown that repetitive exposures to glutamate (100 μM, 3 min, three times at 24-hr intervals) induced a long-lasting synaptic enhancement accompanied by synaptogenesis in rat hippocampal slice cultures, a phenomenon termed RISE (for repetitive LTP-induced synaptic enhancement). To investigate the molecular mechanisms underlying RISE, we first analyzed the time course of gene expression changes between 4 hr and 12 days after repetitive stimulation using an original oligonucleotide microarray: "synaptoarray. " The results demonstrated that changes in the expression of synapse-related genes were induced in two time phases, an early phase of 24-96 hr and a late phase of 6-12 days after the third stimulation. Comprehensive screening at 48 hr after the third stimulation using commercially available high-density microarrays provided candidate genes responsible for RISE. From real-time PCR analysis of these and related genes, two categories of genes were identified, 1) genes previously reported to be induced by physiological as well as epileptic activity (bdnf, grm5, rgs2, syt4, ania4/carp/dclk) and 2) genes involved in cofilin-based regulation of actin filament dynamics (ywhaz, ssh1l, pak4, limk1, cfl). In the first category, synaptotagmin 4 showed a third stimulation-specific up-regulation also at the protein level. Five genes in the second category were coordinately upregulated by the second stimulation, resulting in a decrease in cofilin phosphorylation and an enhancement of actin filament dynamics. In contrast, after the third stimulation, they were differentially regulated to increase cofilin phosphorylation and enhance actin polymerization, which may be a key step leading to the establishment of RISE.

Original languageEnglish
Pages (from-to)2911-2922
Number of pages12
JournalJournal of neuroscience research
Volume88
Issue number13
DOIs
Publication statusPublished - 2010 Oct 1
Externally publishedYes

Fingerprint

Glutamic Acid
Gene Expression
Actin Depolymerizing Factors
Genes
Actin Cytoskeleton
Phosphorylation
Synaptotagmins
Carps
Oligonucleotide Array Sequence Analysis
Polymerization
Synapses
Actins
Real-Time Polymerase Chain Reaction
Up-Regulation
Proteins

Keywords

  • DNA microarray
  • Long-lasting plasticity
  • Long-term potentiation
  • Repetitive stimulation
  • Synaptogenesis

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Analysis of gene expression changes associated with long-lasting synaptic enhancement in hippocampal slice cultures after repetitive exposures to glutamate. / Kawaai, Katsuhiro; Tominaga-Yoshino, Keiko; Urakubo, Tomoyoshi; Taniguchi, Naoko; Kondoh, Yasumitsu; Tashiro, Hideo; Ogura, Akihiko; Tashiro, Tomoko.

In: Journal of neuroscience research, Vol. 88, No. 13, 01.10.2010, p. 2911-2922.

Research output: Contribution to journalArticle

Kawaai, K, Tominaga-Yoshino, K, Urakubo, T, Taniguchi, N, Kondoh, Y, Tashiro, H, Ogura, A & Tashiro, T 2010, 'Analysis of gene expression changes associated with long-lasting synaptic enhancement in hippocampal slice cultures after repetitive exposures to glutamate', Journal of neuroscience research, vol. 88, no. 13, pp. 2911-2922. https://doi.org/10.1002/jnr.22457
Kawaai, Katsuhiro ; Tominaga-Yoshino, Keiko ; Urakubo, Tomoyoshi ; Taniguchi, Naoko ; Kondoh, Yasumitsu ; Tashiro, Hideo ; Ogura, Akihiko ; Tashiro, Tomoko. / Analysis of gene expression changes associated with long-lasting synaptic enhancement in hippocampal slice cultures after repetitive exposures to glutamate. In: Journal of neuroscience research. 2010 ; Vol. 88, No. 13. pp. 2911-2922.
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