WorldCat Identities

Sakimura, Kenji

Overview
Works: 21 works in 21 publications in 1 language and 36 library holdings
Roles: Other
Publication Timeline
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Most widely held works by Kenji Sakimura
<> by Michaela Kerstin Müller( )

1 edition published in 2018 in English and held by 2 WorldCat member libraries worldwide

Mice deficient in the C-terminal domain of TAR DNA-binding protein 43 develop age-dependent motor dysfunction associated with impaired Notch1−Akt signaling pathway by Kohei Nishino( )

1 edition published in 2019 in English and held by 2 WorldCat member libraries worldwide

Correction to: Female-biased sexual dimorphism of corticotropin-releasing factor neurons in the bed nucleus of the stria terminalis by Katsuya Uchida( )

1 edition published in 2019 in English and held by 2 WorldCat member libraries worldwide

Higher visual responses in the temporal cortex of mice by Nana Nishio( )

1 edition published in 2018 in English and held by 2 WorldCat member libraries worldwide

Dense projection of Stilling's nucleus spinocerebellar axons that convey tail proprioception to the midline area in lobule VIII of the mouse cerebellum by Yuanjun Luo( )

1 edition published in 2020 in English and held by 2 WorldCat member libraries worldwide

NMDA receptor subunits have different roles in NMDA-induced neurotoxicity in the retina by Ning Bai( )

1 edition published in 2013 in English and held by 2 WorldCat member libraries worldwide

Female-biased sexual dimorphism of corticotropin-releasing factor neurons in the bed nucleus of the stria terminalis by Katsuya Uchida( )

1 edition published in 2019 in English and held by 2 WorldCat member libraries worldwide

<> by Shota Katori( )

1 edition published in 2017 in English and held by 2 WorldCat member libraries worldwide

Distribution of Caskin1 protein and phenotypic characterization of its knockout mice using a comprehensive behavioral test battery by Tayo Katano( )

1 edition published in 2018 in English and held by 2 WorldCat member libraries worldwide

The number and distribution of AMPA receptor channels containing fast kinetic GluA3 and GluA4 subunits at auditory nerve synapses depend on the target cells by María E Rubio( )

1 edition published in 2017 in English and held by 2 WorldCat member libraries worldwide

Orexin modulates behavioral fear expression through the locus coeruleus by Shingo Soya( )

1 edition published in 2017 in English and held by 2 WorldCat member libraries worldwide

Impaired cortico-striatal excitatory transmission triggers epilepsy by Hiroyuki Miyamoto( )

1 edition published in 2019 in English and held by 2 WorldCat member libraries worldwide

Microglia permit climbing fiber elimination by promoting GABAergic inhibition in the developing cerebellum by Hisako Nakayama( )

1 edition published in 2018 in English and held by 2 WorldCat member libraries worldwide

Non-coding cis-element of Period2 is essential for maintaining organismal circadian behaviour and body temperature rhythmicity by Masao Doi( )

1 edition published in 2019 in English and held by 2 WorldCat member libraries worldwide

Cdk5/p35 is required for motor coordination and cerebellar plasticity( )

1 edition published in 2014 in English and held by 1 WorldCat member library worldwide

Abstract Previous studies have implicated the role of Purkinje cells in motor learning and the underlying mechanisms have also been identified in great detail during the last decades. Here we report that cyclin-dependent kinase 5 (Cdk5)/p35 in Purkinje cell also contributes to synaptic plasticity. We previously showed that p35−/− (p35 KO) mice exhibited a subtle abnormality in brain structure and impaired spatial learning and memory. Further behavioral analysis showed that p35 KO mice had a motor coordination defect, suggesting that p35, one of the activators of Cdk5, together with Cdk5 may play an important role in cerebellar motor learning. Therefore, we created Purkinje cell-specific conditional Cdk5/p35 knockout (L7-p35 cKO) mice, analyzed the cerebellar histology and Purkinje cell morphology of these mice, evaluated their performance with balance beam and rota-rod test, and performed electrophysiological recordings to assess long-term synaptic plasticity. Our analyses showed that Purkinje cell-specific deletion of Cdk5/p35 resulted in no changes in Purkinje cell morphology but severely impaired motor coordination. Furthermore, disrupted cerebellar long-term synaptic plasticity was observed at the parallel fiber-Purkinje cell synapse in L7-p35 cKO mice. These results indicate that Cdk5/p35 is required for motor learning and involved in long-term synaptic plasticity. Purkinje cells play an important role in motor learning, the underlying mechanisms of which have been studied during the last two decades. We report here that the ablation of Cdk5/p35 in Purkinje cells impairs motor coordination, along with deficits in the cerebellar synaptic plasticity, which gives new insights into the mechanism of synaptic plasticity in Purkinje cells
Determination of kainate receptor subunit ratios in mouse brain using novel chimeric protein standards( )

1 edition published in 2015 in English and held by 1 WorldCat member library worldwide

Abstract: Kainate-type glutamate receptors (KARs) are tetrameric channels assembled from GluK1-5. GluK1-3 are low-affinity subunits that form homomeric and heteromeric KARs, while GluK4 and GluK5 are high-affinity subunits that require co-assembly with GluK1-3 for functional expression. Although the subunit composition is thought to be highly heterogeneous in the brain, the distribution of KAR subunits at the protein level and their relative abundance in given regions of the brain remain largely unknown. In the present study, we titrated C-terminal antibodies to each KAR subunit using chimeric GluA2-GluK fusion proteins, and measured their relative abundance in the P2 and post-synaptic density (PSD) fractions of the adult mouse hippocampus and cerebellum. Analytical western blots showed that GluK2 and GluK3 were the major KAR subunits, with additional expression of GluK5 in the hippocampus and cerebellum. In both regions, GluK4 was very low and GluK1 was below the detection threshold. The relative amount of low-affinity subunits (GluK2 plus GluK3) was several times higher than that of high-affinity subunits (GluK4 plus GluK5) in both regions. Of note, the highest ratio of high-affinity subunits to low-affinity subunits was found in the hippocampal PSD fraction (0.32), suggesting that heteromeric receptors consisting of high- and low-affinity subunits highly accumulate at hippocampal synapses. In comparison, this ratio was decreased to 0.15 in the cerebellar PSD fraction, suggesting that KARs consisting of low-affinity subunits are more prevalent in the cerebellum. Therefore, low-affinity KAR subunits are predominant in the brain, with distinct subunit combinations between the hippocampus and cerebellum. Kainate receptors, an unconventional member of the iGluR receptor family, have a tetrameric structure assembled from low-affinity (GluK1-3) and high-affinity (GluK4 and GluK5) subunits. We used a simple but novel procedure to measure the relative abundance of both low- and high-affinity subunits. This method revealed that the relative amount of GluK2 plus GluK3 subunits was several times higher than that of GluK4 plus GluK5 subunits, in both the hippocampus and cerebellum. Abstract : Kainate receptors, an unconventional member of the iGluR receptor family, have a tetrameric structure assembled from low-affinity (GluK1-3) and high-affinity (GluK4 and GluK5) subunits. We used a simple but novel procedure to measure the relative abundance of both low- and high-affinity subunits. This method revealed that the relative amount of GluK2 plus GluK3 subunits was several times higher than that of GluK4 plus GluK5 subunits, in both the hippocampus and cerebellum
Pharmacological properties of SAK3, a novel T-type voltage-gated Ca2+ channel enhancer( )

1 edition published in 2017 in English and held by 1 WorldCat member library worldwide

Abstract: T-type voltage-gated Ca 2+ channels (T-VGCCs) function in the pathophysiology of epilepsy, pain and sleep. However, their role in cognitive function remains unclear. We previously reported that the cognitive enhancer ST101, which stimulates T-VGCCs in rat cortical slices, was a potential Alzheimer's disease therapeutic. Here, we introduce a more potent T-VGCC enhancer, SAK3 (ethyl 82 methyl-22 4-dioxo-2-(piperidin-1-yl)-22 -spiro[cyclopentane-1, 32 imidazo [1, 2-a]pyridin]-2-ene-3-carboxylate), and characterize its pharmacological properties in brain. Based on whole cell patch-clamp analysis, SAK3 (0.01-10nM) significantly enhanced Cav3.1 currents in neuro2A cells ectopically expressing Cav3.1. SAK3 (0.1-10nMnM) also enhanced Cav3.3 but not Cav3.2 currents in the transfected cells. Notably, Cav3.1 and Cav3.3T-VGCCs were localized in cholinergic neurve systems in hippocampus and in the medial septum. Indeed, acute oral administration of SAK3 (0.5mg/kg, p.o.), but not ST101 (0.5mg/kg, p.o.) significantly enhanced acetylcholine (ACh) release in the hippocampal CA1 region of naïve mice. Moreover, acute SAK3 (0.5mg/kg, p.o.) administration significantly enhanced hippocampal ACh levels in olfactory-bulbectomized (OBX) mice, rescuing impaired memory-related behaviors. Treatment of OBX mice with the T-VGCC-specific blocker NNC 55-0396 (12.5mg/kg, i.p.) antagonized both enhanced ACh release and memory improvements elicited by SAK3 administration. We also observed that SAK3-induced ACh releases were significantly blocked in the hippocampus from Cav3.1 knockout (KO) mice. These findings suggest overall that T-VGCCs play a key role in cognition by enhancing hippocampal ACh release and that the cognitive enhancer SAK3 could be a candidate therapeutic in Alzheimer's disease. Highlights: SAK3 enhances Cav3.1 and Cav3.3T-type Ca 2+ channel currents. SAK3 promotes ACh release in the hippocampus via enhancing T-type Ca 2+ channel. Acute SAK3 administration improves memory deficits in olfactory-bulbectomized mice
Unconventional role of voltage-gated proton channels (VSOP/Hv1) in regulation of microglial ROS production( )

1 edition published in 2017 in English and held by 1 WorldCat member library worldwide

Abstract : Voltage gated proton channel (VSOP/Hv1) has been believed to support reactive oxygen species (ROS) production in microglia. We found that VSOP/Hv1 has also paradoxical suppressive role in microglial ROS production possibly by changing actin dynamics. We also suggested that neuroprotective effect of VSOP/Hv1 deficiency on infarct volume in brain ischemia depends on the age of animals. Abstract: It has been established that voltage-gated proton channels (VSOP/Hv1), encoded by Hvcn1, support reactive oxygen species (ROS) production in phagocytic activities of neutrophils (El Chemaly et al .2010 ) and antibody production in B lymphocytes (Capasso et al .2010 ). VSOP/Hv1 is a potential therapeutic target for brain ischemia, since Hvcn1 deficiency reduces microglial ROS production and protects brain from neuronal damage (Wu et al .2012 ). In the present study, we report that VSOP/Hv1 has paradoxical suppressive role in ROS production in microglia. Extracellular ROS production was lower in neutrophils of Hvcn1 −/− mice than WT mice as reported. In contrast, it was drastically enhanced in isolated Hvcn1 −/− microglia as compared with cells from WT mice. Actin dynamics was altered in Hvcn1 −/− microglia and intracellular distribution of cytosolic NADPH oxidase subunit, p67, was changed. When expression levels of oxidative stress responsive antioxidant genes were compared between WT and Hvcn1 −/− in cerebral cortex at different ages of animals, they were slightly decreased in Hvcn1 −/− mice at younger stage (1 day, 5 days, 3 weeks old), but drastically increased at aged stage (6 months old), suggesting that the regulation of microglial ROS production by VSOP/Hv1 is age-dependent. We also performed brain ischemic stroke experiments and found that the neuroprotective effect of VSOP/Hv1deficiency on infarct volume depended on the age of animals. Taken together, regulation of ROS production by VSOP/Hv1 is more complex than previously thought and significance of VSOP/Hv1 in microglial ROS production depends on age
Contribution of postsynaptic T-type calcium channels to parallel fibre-Purkinje cell synaptic responses( )

1 edition published in 2016 in English and held by 1 WorldCat member library worldwide

Abstract : Key points: At the parallel fibre-Purkinje cell glutamatergic synapse, little or no Ca 2+ entry takes place through postsynaptic neurotransmitter receptors, although postsynaptic calcium increases are clearly involved in the synaptic plasticity. Postsynaptic voltage-gated Ca 2+ channels therefore constitute the sole rapid postsynaptic Ca 2+ signalling mechanism, making it essential to understand how they contribute to the synaptic signalling. Using a selective T-type calcium channel antagonist, we describe a T-type component of the EPSC that is activated by the AMPA receptor-mediated depolarization of the spine and thus will contribute to the local calcium dynamics. This component can amount up to 20% of the EPSC, and this fraction is maintained even at the high frequencies sometimes encountered in sensory processing. Modelling based on our biophysical characterization of T-type calcium channels in Purkinje cells suggests that the brief spine EPSCs cause the activated T-type channels to deactivate rather than inactivate, enabling repetitive activation. Abstract: In the cerebellum, sensory information is conveyed to Purkinje cells (PC) via the granule cell/parallel fibre (PF) pathway. Plasticity at the PF-PC synapse is considered to be a mechanism of information storage in motor learning. The induction of synaptic plasticity in the cerebellum and elsewhere usually involves intracellular Ca 2+ signals. Unusually, postsynaptic Ca 2+ signalling in PF-PC spines does not involve ionotropic glutamatergic receptors because postsynaptic NMDA receptors are absent and the AMPA receptors are Ca 2+ -impermeable; postsynaptic voltage-gated Ca 2+ channels therefore constitute the sole rapid Ca 2+ signalling mechanism. Low-threshold activated T-type calcium channels are present at the synapse, although their contribution to PF-PC synaptic responses is unknown. Taking advantage of 3, 5-dichloro- N -[1-(2, 2-dimethyl-tetrahydro-pyran-4-ylmethyl)-4-fluoro-piperidin-4-ylmethyl]-benzamide, a selective T-type channel antagonist, we show in the mouse that inhibition of these channels reduces PF-PC excitatory postsynaptic currents and excitatory postsynaptic potentials by 15-20%. This contribution was preserved during sparse input and repetitive activity. We characterized the biophysical properties of native T-type channels in young animals and modelled their activation during simulated dendritic excitatory postsynaptic potential waveforms. The comparison of modelled and observed synaptic responses suggests that T-type channels only activate in spines that are strongly depolarized by their synaptic input, a process requiring a high spine neck resistance. This brief and local activation ensures that T-type channels rapidly deactivate, thereby limiting inactivation during repetitive synaptic activity. T-type channels are therefore ideally situated to provide synaptic Ca 2+ entry at PF-PC spines. Key points: At the parallel fibre-Purkinje cell glutamatergic synapse, little or no Ca 2+ entry takes place through postsynaptic neurotransmitter receptors, although postsynaptic calcium increases are clearly involved in the synaptic plasticity. Postsynaptic voltage-gated Ca 2+ channels therefore constitute the sole rapid postsynaptic Ca 2+ signalling mechanism, making it essential to understand how they contribute to the synaptic signalling. Using a selective T-type calcium channel antagonist, we describe a T-type component of the EPSC that is activated by the AMPA receptor-mediated depolarization of the spine and thus will contribute to the local calcium dynamics. This component can amount up to 20% of the EPSC, and this fraction is maintained even at the high frequencies sometimes encountered in sensory processing. Modelling based on our biophysical characterization of T-type calcium channels in Purkinje cells suggests that the brief spine EPSCs cause the activated T-type channels to deactivate rather than inactivate, enabling repetitive activation
 
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English (20)