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機能形態学機能組織学(解剖学第二)

研究室概要

外傷や神経変性疾患、加齢、ストレスにより脳や神経がダメージを受けると著しくその機能は低下します。これは神経細胞がダメージに対して脆弱で変性・脱落するためです。当教室では、ダメージという緊急事態に応答して神経細胞やその周囲細胞が作動させる様々なメカニズムの基本原理を分子レベルで明らかにすることを目指しています。こうした基礎的研究が損傷や疾患によりダメージを受けた神経細胞を積極的に保護し修復を促す治療や創薬の基盤になると考えています。さらに、神経は脳だけではなく全身に張り巡らされ多様な臓器に豊富に分布することにも注目しています。臓器が外傷や疾患により傷つくと同時に神経も傷つきます。するとダメージを受けた神経から臓器・組織に向けて恒常性を維持したり修復を促す指令が出ると考えられ、その仕組みを解明する研究も進めています。組織学的解析、分子生物学・生化学的解析、各種網羅的解析、イメージングなど幅広く先端技術を取り入れ、ダメージに対する神経細胞の応答に光を当てる独自のアプローチから疾患病態解明に挑み社会医療に貢献したいと考えています。

 

研究内容について詳しくは研究室独自ホームページをご覧ください。

研究プロジェクト

主要な研究テーマは以下のとおりです

  1. ダメージに対する神経細胞の耐性獲得メカニズム　

▶︎ 運動ニューロンにおけるタンパク質、オルガネラの恒常性維持と破綻

▶︎ アルツハイマー病モデルでの非神経細胞による損傷微小環境制御

▶︎ 老化に関わる神経細胞のダメージ応答

2．ダメージを受けた臓器・組織の修復を神経が促すメカニズム

▶︎ 神経依存性の創傷治癒メカニズム

▶︎ 慢性ストレスに関わる神経回路とその分子メカニズム

教員

構成員名役職所属
桐生 寿美子 教授 機能組織学
永田健一 特任講師 機能組織学
松本早紀子 講師 機能組織学
若月康次 助教 機能組織学

研究実績

  • 2024年
    1. Wakatsuki K, Kiryu-Seo S, Yasui M, Yokota H, Kida H, Konishi H, Kiyama H. Repeated cold stress, an animal model for fibromyalgia, elicits proprioceptor-induced chronic pain with microglial activation in mice. J Neuroinflammation. 2024; 21(1):25.
    2. Elgendy M, Tamada H, Taira T, Iio Y, Kawamura A, Kunogi A, Mizutani Y, Kiyama H. Dynamic changes in endoplasmic reticulum morphology and its contact with the plasma membrane in motor neurons in response to nerve injury. Cell Tissue Res. in press.
  • 2022年
    1. Konishi H, Koizumi S, Kiyama H. Phagocytic astrocytes: Emerging from the shadows of microglia (Review). Glia. 2022; 70(6):1009-1026.
    2. Kiryu-Seo S, Matsushita R, Tashiro Y, Yoshimura T, Iguchi Y, Katsuno M, Takahashi R, Kiyama H. Impaired disassembly of the axon initial segment restricts mitochondrial entry into damaged axons. EMBO J. 2022; 41(20):e110486.
    3. Shishioh N, Kiryu-Seo S, Abe-Dohmae S, Yokoyama S, Kiyama H. Expression of ATP-binding cassette transporter A1 is induced by nerve injury and its deficiency affects neurite tip morphology and elongation in cultured neurons. J Chem Neuroanat. 2022; 125:102164.
  • 2021年
    1. Sato T, Konishi H, Tamada H, Nishiwaki K, Kiyama H. Morphology, localization, and postnatal development of dural macrophages. Cell Tissue Res. 2021; 157(4):1196-1206.
    2. Li C, Konishi H, Nishiwaki K, Sato K, Miyata T, Kiyama H. A mouse model of microglia-specific ablation in the embryonic central nervous system. Neurosci Res. 2021; 173:54-61.
    3. Tamada H, Kiryu-Seo S, Sawada S, Kiyama H. Axonal injury alters the extracellular glial environment of the axon initial segment and allows substantial mitochondrial influx into axon initial segment. J Comp Neurol. 2021; 529(16):3621-3632.
  • 2020年
    1. Konishi H, Okamoto T, Hara Y, Komine O, Tamada H, Maeda M, Osako F, Kobayashi M, Nishiyama A, Kataoka Y, Takai T, Udagawa N, Jung S, Ozato K, Tamura T, Tsuda M, Yamanaka K, Ogi T, Sato K, Kiyama H. Astrocytic phagocytosis is a compensatory mechanism for microglial dysfunction. EMBO J. 2020; 39(22):e104464.
    2. Konishi H, Kiyama H. Non-pathological roles of microglial TREM2/DAP12: TREM2/DAP12 regulates the physiological functions of microglia from development to aging (Review). Neurochem Int. 2020; 141:104878.
  • 2019年
    1. Kiryu-Seo S, Kiyama H. Mitochondrial behavior during axon regeneration/degeneration in vivo (Review). Neurosci Res. 2019; 139:42-47.
    2. Konishi H, Kiyama H, Ueno M. Dual functions of microglia in the formation and refinement of neural circuits during development (Review). Int J Dev Neurosci. 2019; 77:18-25.
    3. Kiryu-Seo S, Nagata K, Saido TC, Kiyama H. New Insights of a Neuronal Peptidase DINE/ECEL1: Nerve Development, Nerve Regeneration and Neurogenic Pathogenesis (Review). Neurochem Res. 2019; 44(6):1279-1288.
    4. Yasui M, Menjyo Y, Tokizane K, Shiozawa A, Tsuda M, Inoue K, Kiyama H. Hyperactivation of proprioceptors induces microglia-mediated long-lasting pain in a rat model of chronic fatigue syndrome. J Neuroinflammation. 2019; 16(1):67.
    5. Sayo A, Konishi H, Kobayashi M, Kano K, Kobayashi H, Hibi H, Aoki J, Kiyama H. GPR34 in spinal microglia exacerbates neuropathic pain in mice. 2019; J Neuroinflammation. 16(1):82.
  • 2018年
    1. Konishi H, Kiyama H. Microglial TREM2/DAP12 Signaling: A Double-Edged Sword in Neural Diseases (Review). Front Cell Neurosci. 2018; 12:206.
  • 2017年
    1. Nagata K*, Takahashi M, Kiryu-Seo S, Kiyama H*, Saido TC*. Distinct functional consequences of ECEL1/DINE missense mutations in the pathogenesis of congenital contracture disorders. Acta Neuropathol Commun. 2017; 5(1):83. *Corresponding authors
    2. Wei L, Tokizane K, Konishi H, Yu HR, Kiyama H. Agonists for G-protein-coupled receptor 84 (GPR84) alter cellular morphology and motility but do not induce pro-inflammatory responses in microglia. J Neuroinflammation. 2017; 14(1):198.
    3. Konishi H, Kobayashi M, Kunisawa T, Imai K, Sayo A, Malissen B, Crocker PR, Sato K, Kiyama H. Siglec-H is a microglia-specific marker that discriminates microglia from CNS-associated macrophages and CNS-infiltrating monocytes. Glia. 2017; 65(12):1927-1943.
    4. Kaneko A, Kiryu-Seo S, Matsumoto S, Kiyama H. Damage-induced neuronal endopeptidase (DINE) enhances axonal regeneration potential of retinal ganglion cells after optic nerve injury. Cell Death Dis. 2017; 8(6):e2847.
    5. Konishi H, Ohgami N, Matsushita A, Kondo Y, Aoyama Y, Kobayashi M, Nagai T, Ugawa S, Yamada K, Kato M, Kiyama H. Exposure to diphtheria toxin during the juvenile period impairs both inner and outer hair cells in C57BL/6 mice. Neuroscience. 2017; 351:15-23.
    6. Tamada H, Kiryu-Seo S, Hosokawa H, Ohta K, Ishihara N, Nomura M, Mihara K, Nakamura KI, Kiyama H. Three-dimensional analysis of somatic mitochondrial dynamics in fission-deficient injured motor neurons using FIB/SEM. J Comp Neurol. 2017; 525(11):2535-2548.
    7. Tokizane K, Konishi H, Makide K, Kawana H, Nakamuta S, Kaibuchi K, Ohwada T, Aoki J, Kiyama H. Phospholipid localization implies microglial morphology and function via Cdc42 in vitro. Glia. 2017; 65(5):740-755.
  • 2016年
    1. Kobayashi M, Konishi H, Sayo A, Takai T, Kiyama H. TREM2/DAP12 signal elicits pro-inflammatory response in microglia and exacerbates neuropathic pain. J Neurosci. 2016; 36(43):11138-50
    2. Tamada H, Kiyama H. Suppression of c-Kit signaling induces adult neurogenesis in the mouse intestine after myenteric plexus ablation with benzalkonium chloride. Sci Rep. 2016; 6: 32100.
    3. Kiryu-Seo S, Tamada H, Kato Y, Yasuda K, Ishihara N, Nomura M, Mihara K, Kiyama H. Mitochondrial fission is an acute and adaptive response in injured motor neurons. Sci Rep. 2016; 6: 28331.
    4. Matsumoto S, Kiryu-Seo S, Kiyama H. Motor Nerve Arborization Requires Proteolytic Domain of Damage-Induced Neuronal Endopeptidase (DINE) during Development. J Neurosci. 2016; 36(17): 4744-57.
    5. Nagata K*, Kiryu-Seo S, Tamada H, Okuyama-Uchimura F, Kiyama H*, Saido TC*. ECEL1 mutation implicates impaired axonal arborization of motor nerves in the pathogenesis of distal arthrogryposis. Acta neuropathologica. 2016; 132(1): 111-26. *Corresponding authors
    6. Rashwan A, Konishi H, El-Sharaby A, Kiyama H. Ontogeny and innervation of taste buds in mouse palatal gustatory epithelium. J Chem Neuroanat. 2016; 71: 26-40.
    7. Jung J, Uesugi N, Jeong NY, Park BS, Konishi H, Kiyama H. Increase of transcription factor EB (TFEB) and lysosomes in rat DRG neurons and their transportation to the central nerve terminal in dorsal horn after nerve injury. Neuroscience. 2016; 313: 10-22.
  • 2015年
    1. Kobayashi M, Konishi H, Takai T, Kiyama H. A DAP12-dependent signal promotes pro-inflammatory polarization in microglia following nerve injury and exacerbates degeneration of injured neurons. Glia. 2015; 63(6): 1073-82.
    2. Tamada H, Kiyama H. Existence of c-Kit negative cells with ultrastructural features of interstitial cells of Cajal in the subserosal layer of the W/Wv mutant mouse colon. J Smooth Muscle Res. 2015; 51: 1-9.
  • 2014年
    1. Yasui M, Yoshimura T, Takeuchi S, Tokizane K, Tsuda M, Inoue K, Kiyama H. A chronic fatigue syndrome model demonstrates mechanical allodynia and muscular hyperalgesia via spinal microglial activation. Glia. 2014; 62(9): 1407-17.
    2. Nagata K, Hama I, Kiryu-Seo S, Kiyama H. microRNA-124 is down regulated in nerve-injured motor neurons and it potentially targets mRNAs for KLF6 and STAT3. Neuroscience. 2014; 256: 426-32.
  • 2013年
    1. Konishi H, Matsumoto S, Namikawa K, Kiyama H. N-terminal cleaved pancreatitis-associated protein-III (PAP-III) serves as a scaffold for neurites and promotes neurite outgrowth. J Biol Chem. 2013;288(15):10205-13.
    2. Tokizane K, Konishi H, Yasui M, Ogawa T, Sasaki K, Minamino N, Kiyama H. Continuous stress promotes expression of VGF in melanotroph via suppression of dopamine. Mol Cell Endocrinol. 2013;372(1-2):49-56.
  • 2011年
    1. Kiryu-Seo S, Kiyama H. The nuclear events guiding successful nerve regeneration (Review). Front Mol Neurosci. 2011; 4:53.
  • 2006年
    1. Kiryu-Seo S, Gamo K, Tachibana T, Tanaka K, Kiyama H. Unique anti-apoptotic activity of EAAC1 in injured motor neurons. EMBO J. 2006; 25(14): 3411-21.
  • 2003年
    1. Nakagomi S, Suzuki Y, Namikawa K, Kiryu-Seo S, Kiyama H. Expression of the Activating transcription factor 3 (ATF3) prevents JNK-induced neuronal death by promoting Hsp27 expression and Akt activation. J Neurosci. 2003; 23(12): 5187-96.
  • 2000年
    1. Kiryu-Seo S, Sasaki M, Yokohama H, Nakagomi S, Hirayama T, Aoki S, Wada K, Kiyama H. Damage induced neuronal endopeptidase (DINE) is a unique metallopeptidase expressed in response to neuronal damage and activates superoxide scavengers. Proc. Natl. Acad. Sci. USA. 2000; 97(8):4345-50.
    2. Namikawa K, Honma M, Abe K, Takeda M, Mansur K, Obata t, Miwa A, Okado H, Kiyama H. Akt / Protein kinase B prevents injury-induced motor neuron death and accelerates axonal regeneration. J Neurosci. 2000; 20(8):2875-86.

研究キーワード

神経損傷、神経再生・変性、神経変性疾患、筋萎縮性側索硬化症(ALS)、アルツハイマー病、ニューロン、グリア細胞、オルガネラダイナミクス、神経炎症、慢性ストレス

機能組織学 独自ホームページ

機能組織学　オープンキャンパス

大学院生募集

熱意ある大学院生（修士・博士課程）を募集しています。出身学部は問いません。