Publications (20) View all
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Article: Evidence for cell density affecting C2C12 myogenesis: possible regulation of myogenesis by cell-cell communication.
Kanako Tanaka, Kaori Sato, Tomomi Yoshida, Toshio Fukuda, Kenji Hanamura, Nobuhiko Kojima, Tomoaki Shirao, Takashi Yanagawa, Hideomi Watanabe[show abstract] [hide abstract]
ABSTRACT: Community effect is a phenomenon caused by cell-cell communication during myogenesis. In myogenic C2C12 cells in vitro, the confluent phase is needed for myogenesis induction. To examine the cell-density effect, growth kinetics and myogenic differentiation were investigated in cells plated at four different cell densities. We found that expression of a myogenic differentiation marker was high in a density-dependent manner. At high density, where cell-cell contact was obvious, contact inhibition after the proliferation stage was accompanied by microarray findings demonstrating upregulation of negative regulating cell-cycle markers, including CDKI p21 and the muscle differentiation markers MyoD and myogenin. Interestingly, developmentally regulated protein expression (drebrin) protein expression was also upregulated in a density-dependent manner. These results suggest that contact inhibition after the proliferation stage may induce growth arrest via cell-cell communication through the expression of CDKI p21 and may be responsible for progressing cell fusion.Muscle & Nerve 12/2011; 44(6):968-77. · 2.37 Impact Factor -
Article: Reduced locomotor sensitization induced by methamphetamine and altered gene expression in ICER overexpressing mice.
Wenhua Han, Yukio Takamatsu, Shinya Kasai, Shogo Endo, Tomoaki Shirao, Nobuhiko Kojima, Kazutaka IkedaNihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology 04/2011; 31(2):79-80. -
Article: Differential regional distribution of phosphorylated tau and synapse loss in the nucleus accumbens in tauopathy model mice.
Taiki Kambe, Yumiko Motoi, Ran Inoue, Nobuhiko Kojima, Norihiro Tada, Tetsuya Kimura, Naruhiko Sahara, Shunji Yamashita, Tatsuya Mizoroki, Akihiko Takashima, Kohei Shimada, Koichi Ishiguro, Hiroshi Mizuma, Hirotaka Onoe, Yoshikuni Mizuno, Nobutaka Hattori[show abstract] [hide abstract]
ABSTRACT: Tauopathies differ in terms of the brain regions that are affected. In Alzheimer's disease, basal forebrain and hippocampus are mainly involved, while frontotemporal lobar degeneration affects the frontal and temporal lobes and subcortical nuclei including striatum. Over 90% of human cases of tauopathies are sporadic, although the majority of established tau-transgenic mice have had mutations. This prompted us to establish transgenic mice expressing wild-type human tau (Tg601). Old (>14 months old) Tg601 mice displayed decreased anxiety in the elevated plus maze test and impaired place learning in the Morris water maze test. Immunoblotting of brain tissue identified that soluble tau multimer was increased with aging even though insoluble tau was not observed. In the striatum of old Tg601, the level of AT8- or AT180-positive tau was decreased compared with that of other regions, while PHF-1-positive tau levels remained equal. Phosphorylated tau-positive axonal dilations were present mainly in layers V and VI of the prefrontal cortex. Loss of synaptic dendritic spine and decreased immunohistochemical level of synaptic markers were observed in the nucleus accumbens. In vivo 2-[(18)F]fluoro-2-deoxy-d-glucose positron emission tomography analysis also showed decreased activity exclusively in the nucleus accumbens of living Tg601 mice. In Tg601 mice, the axonal transport defect in the prefrontal cortex-nucleus accumbens pathway may lead to decreased anxiety behavior. Differential distribution of hyperphosphorylated tau may cause region-specific neurodegeneration.Neurobiology of Disease 02/2011; 42(3):404-14. · 5.40 Impact Factor -
SourceAvailable from: Tomoaki Shirao
Article: Inhibitory role of inducible cAMP early repressor (ICER) in methamphetamine-induced locomotor sensitization.
Wenhua Han, Yukio Takamatsu, Hideko Yamamoto, Shinya Kasai, Shogo Endo, Tomoaki Shirao, Nobuhiko Kojima, Kazutaka Ikeda[show abstract] [hide abstract]
ABSTRACT: The inducible cyclic adenosine monophosphate (cAMP) early repressor (ICER) is highly expressed in the central nervous system and functions as a repressor of cAMP response element-binding protein (CREB) transcription. The present study sought to clarify the role of ICER in the effects of methamphetamine (METH). We tested METH-induced locomotor sensitization in wildtype mice, ICER knockout mice, and ICER I-overexpressing mice. Both ICER wildtype mice and knockout mice displayed increased locomotor activity after continuous injections of METH. However, ICER knockout mice displayed a tendency toward higher locomotor activity compared with wildtype mice, although no significant difference was observed between the two genotypes. Moreover, compared with wildtype mice, ICER I-overexpressing mice displayed a significant decrease in METH-induced locomotor sensitization. Furthermore, Western blot analysis and quantitative real-time reverse transcription polymerase chain reaction demonstrated that ICER overexpression abolished the METH-induced increase in CREB expression and repressed cocaine- and amphetamine-regulated transcript (CART) and prodynorphin (Pdyn) expression in mice. The decreased CART and Pdyn mRNA expression levels in vivo may underlie the inhibitory role of ICER in METH-induced locomotor sensitization. Our data suggest that ICER plays an inhibitory role in METH-induced locomotor sensitization.PLoS ONE 01/2011; 6(6):e21637. · 4.09 Impact Factor -
Article: Drebrin a knockout eliminates the rapid form of homeostatic synaptic plasticity at excitatory synapses of intact adult cerebral cortex.
Chiye Aoki, Nobuhiko Kojima, Nicole Sabaliauskas, Lokesh Shah, Tunazzina H Ahmed, John Oakford, Tahir Ahmed, Hiroyuki Yamazaki, Kenji Hanamura, Tomoaki Shirao[show abstract] [hide abstract]
ABSTRACT: Homeostatic synaptic plasticity (HSP) is important for maintaining neurons' excitability within the dynamic range and for protecting neurons from unconstrained long-term potentiation that can cause breakdown of synapse specificity (Turrigiano [2008] Cell 135:422-435). Knowledge of the molecular mechanism underlying this phenomenon remains incomplete, especially for the rapid form of HSP. To test whether HSP in adulthood depends on an F-actin binding protein, drebrin A, mice deleted of the adult isoform of drebrin (DAKO) but retaining the embryonic isoform (drebrin E) were generated. HSP was assayed by determining whether the NR2A subunit of N-methyl-D-aspartate receptors (NMDARs) can rise rapidly within spines following the application of an NMDAR antagonist, D-APV, onto the cortical surface. Electron microscopic immunocytochemistry revealed that, as expected, the D-APV treatment of wild-type (WT) mouse cortex increased the proportion of NR2A-immunolabeled spines within 30 minutes relative to basal levels in hemispheres treated with an inactive enantiomer, L-APV. This difference was significant at the postsynaptic membrane and postsynaptic density (i.e., synaptic junction) as well as at nonsynaptic sites within spines and was not accompanied by spine size changes. In contrast, the D-APV treatment of DAKO brains did not augment NR2A labeling within the spine cytoplasm or at the synaptic junction, even though basal levels of NR2A were not significantly different from those of WT cortices. These findings indicate that drebrin A is required for the rapid (<30 minutes) form of HSP at excitatory synapses of adult cortices, whereas drebrin E is sufficient for maintaining basal NR2A levels within spines.The Journal of Comparative Neurology 07/2009; 517(1):105-21. · 3.81 Impact Factor