Takashi Kubota
Faculty of Pharmaceutical Sciences,Department of Pharmaceutical Sciences | Lecturer |
Last Updated :2025/08/28
■Researcher basic information
Field Of Study
■Career
Career
Educational Background
■Research activity information
Paper
- Impaired Hippocampal Long-Term Potentiation and Memory Deficits upon Haploinsufficiency of MDGA1 Can Be Rescued by Acute Administration of D-Cycloserine
Daiki Ojima; Yoko Tominaga; Takashi Kubota; Atsushi Tada; Hiroo Takahashi; Yasushi Kishimoto; Takashi Tominaga; Tohru Yamamoto
International Journal of Molecular Sciences, 06 Sep. 2024, [Reviewed]
The maintenance of proper brain function relies heavily on the balance of excitatory and inhibitory neural circuits, governed in part by synaptic adhesion molecules. Among these, MDGA1 (MAM domain-containing glycosylphosphatidylinositol anchor 1) acts as a suppressor of synapse formation by interfering with Neuroligin-mediated interactions, crucial for maintaining the excitatory–inhibitory (E/I) balance. Mdga1−/− mice exhibit selectively enhanced inhibitory synapse formation in their hippocampal pyramidal neurons, leading to impaired hippocampal long-term potentiation (LTP) and hippocampus-dependent learning and memory function; however, it has not been fully investigated yet if the reduction in MDGA1 protein levels would alter brain function. Here, we examined the behavioral and synaptic consequences of reduced MDGA1 protein levels in Mdga1+/− mice. As observed in Mdga1−/− mice, Mdga1+/− mice exhibited significant deficits in hippocampus-dependent learning and memory tasks, such as the Morris water maze and contextual fear-conditioning tests, along with a significant deficit in the long-term potentiation (LTP) in hippocampal Schaffer collateral CA1 synapses. The acute administration of D-cycloserine, a co-agonist of NMDAR (N-methyl-d-aspartate receptor), significantly ameliorated memory impairments and restored LTP deficits specifically in Mdga1+/− mice, while having no such effect on Mdga1−/− mice. These results highlight the critical role of MDGA1 in regulating inhibitory synapse formation and maintaining the E/I balance for proper cognitive function. These findings may also suggest potential therapeutic strategies targeting the E/I imbalance to alleviate cognitive deficits associated with neuropsychiatric disorders. - A Bibliometric Analysis of Research Paper Productivity of Japanese Pharmacy Schools
Rei Honda; Yuki Matsubara; Takashi Kubota; Hirofumi Konno; Yutaka Kirino; Yasushi Kishimoto
YAKUGAKU ZASSHI, 01 Mar. 2023, [Reviewed] - Age-dependent impairment of memory and neurofibrillary tangle formation and clearance in a mouse model of tauopathy
Takashi Kubota; Yutaka Kirino
Brain Research, Aug. 2021, [Reviewed] - Spatial and latent memory data in PS2Tg2576 alzheimer's disease mouse model after memantine treatment
Masahisa Matsumura; Kana Sato; Takashi Kubota; Yasushi Kishimoto
Data in Brief, Jun. 2021, [Reviewed] - MDGA1-deficiency attenuates prepulse inhibition with alterations of dopamine and serotonin metabolism: An ex vivo HPLC-ECD analysis
Md Razib Hossain; Mostofa Jamal; Yu Tanoue; Daiki Ojima; Hiroo Takahashi; Takashi Kubota; Tuba M. Ansary; Asuka Ito; Naoko Tanaka; Hiroshi Kinoshita; Yasushi Kishimoto; Tohru Yamamoto
Neuroscience Letters, Jan. 2020, [Reviewed] - Data on amyloid precursor protein accumulation, spontaneous physical activity, and motor learning after traumatic brain injury in the triple-transgenic mouse model of Alzheimer׳s disease
Yasushi Kishimoto; Hajime Shishido; Mayumi Sawanishi; Yasunori Toyota; Masaki Ueno; Takashi Kubota; Yutaka Kirino; Takashi Tamiya; Nobuyuki Kawai
Data in Brief, Dec. 2016, [Reviewed] - Traumatic brain injury accelerates amyloid-β deposition and impairs spatial learning in the triple-transgenic mouse model of Alzheimer’s disease
Hajime Shishido; Yasushi Kishimoto; Nobuyuki Kawai; Yasunori Toyota; Masaki Ueno; Takashi Kubota; Yutaka Kirino; Takashi Tamiya
Neuroscience Letters, Aug. 2016, [Reviewed] - Ameliorative effect of membrane-associated estrogen receptor G protein coupled receptor 30 activation on object recognition memory in mouse models of Alzheimer's disease
Takashi Kubota; Hiroshi Matsumoto; Yutaka Kirino
Journal of Pharmacological Sciences, Jul. 2016, [Reviewed] - Involvement of brain oxidation in the cognitive impairment in a triple transgenic mouse model of Alzheimer's disease: noninvasive measurement of the brain redox state by magnetic resonance imaging
Ishihara Y; Itoh K; Mitsuda Y; Shimada T; Kubota T; Kato C; Song SY; Kobayashi Y; Mori-Yasumoto K; Sekita S; Kirino Y; Yamazaki T; Shimamoto N
Free Radical Research, Sep. 2013, [Reviewed] - カスパーゼ-3:アルツハイマー病における初期神経異常の標的か?
2012 - Hypersensitivity to pentylenetetrazol-induced convulsion in mice lacking the PLC-related inactive protein-1
Yamaguchi T; Kubota T; Kanematsu T; Nakayama K; Hirata M; Yamamoto T
Brain Research, Oct. 2004, [Reviewed] - Activation of brain prostanoid EP3 receptors via arachidonic acid cascade during behavioral suppression induced by Delta 8-tetrahydrocannabinol
Yamaguchi T; Kubota T; Watanabe S; Yamamoto T
Journal of Neurochemistry, Jan. 2004, [Reviewed] - 大麻成分テトラヒドロカンナビノールの異常行動における脳内プロスタグランジン合成経路の役割
Oct. 2002, [Reviewed]
MISC
- Spatial and latent memory data in PS2Tg2576 Alzheimer’s disease mouse model after memantine treatment
Kishimoto Y; Matsumura M; Sato K; Kubota T
Mendeley Data, Feb. 2021 - シナプス形成抑制因子MDGA1の欠失による精神神経疾患様行動異常と、これを抑止する薬剤の探索
Mar. 2020 - All‐transレチノイン酸の短期的投与がアルツハイマー病モデルマウスの認知・行動に及ぼす効果
KURIHARA NAOKAZU; KIRINO YUTAKA; KUBOTA TAKASHI; KISHIMOTO YASUSHI
日本薬学会年会要旨集(CD-ROM), Mar. 2015
(公社)日本薬学会 - アルツハイマー病モデルマウスの認知機能に対する外傷性脳損傷の影響
KISHIMOTO YASUSHI; SHISHIDO HAJIME; KUBOTA TAKASHI; UENO MASAKI; TAMIYA TAKASHI; KAWAI NOBUYUKI; KIRINO YUTAKA
日本薬学会年会要旨集(CD-ROM), Mar. 2014
(公社)日本薬学会 - 3P335 Involvement of arachidonic acid cascade in morphine dependence(Behavior,Poster Presentations)
Kubota Takashi; Kirino Yutaka
Seibutsu Butsuri, 20 Nov. 2007
The Biophysical Society of Japan General Incorporated Association
Books and other publications
Lectures, oral presentations, etc.
- A Cuprizone-induced neuroinflammation;mouse model with;prepulse inhibition deficit exhibited a complementary;yrosine hydroxylase abundance ratio in;he prefrontal cortex;midbrain
02 Dec. 2022 - Behavioral disorders and expression changes of the tyrosine hydroxylase in Cuprizone-induced neuroinflammation mouse model with schizophrenia-like symptoms
KYOKA TSUKUDA; TAKASHI KUBOTA; AOI CHIBA; TAKASHI TOMINAGA; YASUSHI KISHIMOTO; KENTARO NAKASHIMA
Neuroscience 2002 - シナプス形成抑制因子MDGA1/2の欠失は対蹠的な興奮/抑制バランス偏移と行動異常を引き起こすが、成年期の薬剤投与により回復できる
02 Jul. 2022 - ジャワショウガ抽出物trans-bangleneのタウオパチーモデルマウスの記憶障害に対する効果
08 Mar. 2022 - Acute neuroinflammation induced by short-term treatment with Cuprizone leads to behavioral disorders similar to schizophrenia
30 Aug. 2021 - 抑制性シナプス抑制因子MDGA1のヘミ欠損は海馬 LTPの低下と学習・記憶異常を引き起こすが、サイクロセリンの急性投与により回復する
29 Jul. 2021 - Cuprizone短期投与による脳内炎症モデルマウスは統合失調症様精神行動障害を示す
29 Jul. 2021 - Cuprizone短期投与脳内炎症モデルマウスは統合失調症様精神行動障害を示す
22 May 2021 - MDGA1ノックアウトマウスの社会性行動に対するD-サイクロセリンの効果
27 Mar. 2021 - タウタンパク質発現期間依存的な記憶およびタウタンパク質代謝の障害
27 Mar. 2020 - Preventive effects of dietary intake of green algae on cuprizone-induced neuroinflammation in mouse
03 Dec. 2019 - 薬学部の研究生産性に関する調査研究
09 Nov. 2019 - 「タラウミジン誘導体の短段階合成法とアルツハイマー病モデルマウスに対する認知機能改善活性
22 Mar. 2019 - Age-dependent impairment of memory, neurofibrillary tangle formation and clearance in a mouse model of tauopathy
14 Mar. 2019 - Traumatic brain injury accelerates amyloid-b deposition and impairs learning and memory in the triple-transgenic mouse model of Alzheimer
Yutaka Kirino; Hajime Shishido; Nobuyui Kawai; Yasunori Toyota; Takashi Tamiya; Takashi Kubota; Masaki Ueno; Yasushi Kishimoto
Neuroscience 2017 - アルツハイマー病モデルマウスのα7ニコチン性アセチルコリン受容体を介した学習改善作用におけるmicroRNA-134の効果
24 Mar. 2017 - アルツハイマー病モデルマウスの物体認識記憶におけるmicroRNA-132の2相性の効果
26 Mar. 2016 - α7 ニコチン性アセチルコリン受容体作動薬の作業記憶増強作用におけるマイクロRNA-134 の関与
26 Mar. 2015 - All-trans レチノイン酸の短期的投与がアルツハイマー病モデルマウスの認知・行動 に及ぼす効果
26 Mar. 2015 - アルツハイマー病モデルマウスの物体認識記憶におけるmicroRNA-132の役割
27 Mar. 2014 - アルツハイマー病モデルマウスの認知機能に対する外傷性脳損傷の影響
27 Mar. 2014 - Biphasic effect of microRNA-132 on object recognition memory in Alzheimer’s disease mouse models
19 Mar. 2014 - 外傷性脳損傷に伴うアルツハイマー病誘発の分子機構の解明
11 Oct. 2013 - 作業記憶おける細胞膜結合型エストロゲン受容体GPR30の関与
27 Mar. 2013 - Involvement of membrane-associated estrogen receptor GPR30 in the object recognition memory in Alzheimer's disease mouse models
21 Mar. 2013 - 作業記憶および物体認識記憶における細胞膜結合型エストロゲン受容体GPR30の関与
14 Mar. 2013 - アルツハイマー病およびプリオン病モデルマウスを用いた瞬目反射条件付けの解析
14 Mar. 2013 - アルツハイマー病モデルマウスの物体認知記憶における細胞膜貫通型エストロゲン受容体GPR30の役割
29 Mar. 2012 - Involvement of microRNA-134 in the working memory-enhancing effect of nicotinic acetylcholine receptor agonist
14 Mar. 2012 - Contribution of & alpha-7 nicotinic acetylcholine receptor to the classical eyeblink conditioning in Alzheimer’s disease model mice
20 Sep. 2010 - 老化マウス及びアルツハイマー痴呆症マウスモデルにおける瞬目反射条件付けに対するニコチンの効果
28 Jul. 2010 - 老化マウスおよびアルツハイマー病モデルマウスの瞬目反射条件付け学習におけるニコチン性アセチルコリン受容体の関与
16 Mar. 2010 - Contribution of nicotinic acetylcholine receptor to the classical eyeblink conditioning in aged mice and Alzheimer’s disease model mice
30 Oct. 2009 - Involvement of brain cannabinoid system to trace eyeblink classical conditioning in diet-induced obese mice
03 Dec. 2008 - Involvement of arachidonic acid cascade in morphine dependence
21 Dec. 2007 - 肥満モデルマウスの瞬目反射条件付け学習におけるカンナビノイドの関与
16 Jun. 2007 - 肥満モデルマウスにおける瞬目反射条件付け学習に対するカンナビノイシステムの関与
28 Mar. 2007 - Influence of cannabinoid system on the classical eyeblink conditioning in diet-induced obese mice
14 Mar. 2007 - モルヒネ探索行動の再燃および身体依存形成におけるアラキドン酸カスケードの関与
06 Jul. 2005 - モルヒネ探索行動の再燃および身体依存形成に対するアラキドン酸カスケードの関与
21 Mar. 2005 - モルヒネ自己摂取行動の発現に、アラキドン酸カスケードが関与する
28 Nov. 2003 - 薬物自己投与法を用いてのモルヒネ報酬効果発現におけるアラキドン酸カスケードの関与
08 Oct. 2003 - Involvement of arachidonic acid cascade in suppression of lever pressing behavior by repeated treatment of Δ8-tetrahydrocannabinol
24 Mar. 2003 - Repeated Δ8-tetrahyrocannabinol enhances cyclooxygenase protein expression in the rat brain
15 Mar. 2002 - Δ8-テトラヒドロカンナビノールによるシクロオキシゲナーゼの発現変化
Aug. 2001
Research Themes
- Learning and Memory Performance of Alzheimer Disease Mouse Model with Mutant Human Tau Protein
Grant-in-Aid for Scientific Research (C)
Tokushima Bunri University
Apr. 2016 - Mar. 2020
rTg4510 mice constitutively express mutant human tau protein until transgene expression is inactivated by administration of the doxycycline (DOX). In 6-month-old (young) rTg4510 mice, the hippocampus dependent learning abilities including spatial memory, object recognition memory, and trace eyeblink conditioning were impaired. These impairments were reduced by pre-treatment with DOX for 2 months. In parallel, the expression of NFTs decreased in DOX-treated group. 10-month-old (aged) rTg4510 mice showed severe recognition impairment and increased levels of NFTs. Treatment with DOX could not ameliorate the tau pathology in aged rTg4510 mice as well as DOX-untreated group. Since the amount of autophagy markers decreased along with the amelioration of tau pathology, clearance mechanisms of NFTs via autophagy have kept normal functions in 4- to 6-month-old mice while, in 10-month-old mice, clearance system may reach a saturation level. - An Attempt to Detect a Neural Activity Change during Eyeblink Conditioning in Monkeys with PET Imaging
Grant-in-Aid for Scientific Research (C)
Tokushima Bunri University
Apr. 2012 - Mar. 2016
We developed a system which enables us to measure eyeblink conditioning in a monkey species (Macaca mulatta) with a brain size suitable for PET imaging. Eyeblinking was monitored simultaneously by orbicularis oculi electromyographic measurements and a high-speed camera. This system based on the two different principles yielded an interesting finding that the probability of observing a conditioned response in a given trial was not influenced by whether the monkeys closed their eyelids just before conditioned stimulus, suggesting that this memory could be expressed independently of wakefulness.
We tried to gain PET imaging using a selective agonist cannabinoid-1 receptor tracer [11C]CB-119. However, the attempt was not completed due to the limited availability of expensive animals and PET ligands. Nevertheless, this study presents a novel system for cognitive assessment in monkeys that will be useful for elucidating the neural mechanisms of implicit learning in nonhuman primates. - マウス瞬目反射学習に小脳は不要か?
2007 - 2008 - A study on molecular and neural mechanism of eyeblink conditioning
Grant-in-Aid for Scientific Research (A)
2005 - 2008