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• Slow progression of sciatic nerve degeneration and regeneration after loose ligation through microglial activation and decreased KCC2 levels in the mouse spinal cord ventral horn.

  Yafuso T, Kosaka Y, Shimizu-Okabe C, Okura N, Kobayashi S, Kim J, Matsuda K, Kinjo D, Okabe A, Takayama C

  Neuroscience research   177   52 - 63   2022.04 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  Peripheral nerve injury affects motor functions. To reveal the mechanisms underlying motor dysfunction and recovery after nerve compression, which have not been precisely examined, we investigated the temporal relationship among changes in motor function, nerve histopathology, and marker molecule expression in the spinal cord after loose ligation of the mouse sciatic nerve. After ligation, sciatic motor function suddenly declined, and axons gradually degenerated. During degeneration, galanin was localized in motor neuron cell bodies. Then, in the ventral horn, microglia were activated, and expression of choline acetyltransferase (ChAT), a synthetic enzyme of acetylcholine, and potassium chloride co-transporter 2 (KCC2), which shifts the action of γ-amino butyric acid (GABA) and glycine to inhibitory, decreased. Motor function recovery was insufficient although axonal regeneration was complete. ChAT levels gradually recovered during axonal regeneration. When regeneration was nearly complete, microglial activation declined, and KCC2 expression started to increase. The KCC2 level sufficiently recovered when axonal regeneration was complete, suggesting that the excitatory action of GABA/glycine may participate in axonal regeneration. Furthermore, these changes proceeded slower than those after severance, suggesting that loose ligation, compression, may mediate slower progression of degeneration and regeneration than severance, and these changes may cause the motor dysfunction and its recovery.

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• Developmental Formation of the GABAergic and Glycinergic Networks in the Mouse Spinal Cord.

  Chigusa Shimizu-Okabe, Shiori Kobayashi, Jeongtae Kim, Yoshinori Kosaka, Masanobu Sunagawa, Akihito Okabe, Chitoshi Takayama

  International journal of molecular sciences   23 ( 2 )   2022.01 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  Gamma-aminobutyric acid (GABA) and glycine act as inhibitory neurotransmitters. Three types of inhibitory neurons and terminals, GABAergic, GABA/glycine coreleasing, and glycinergic, are orchestrated in the spinal cord neural circuits and play critical roles in regulating pain, locomotive movement, and respiratory rhythms. In this study, we first describe GABAergic and glycinergic transmission and inhibitory networks, consisting of three types of terminals in the mature mouse spinal cord. Second, we describe the developmental formation of GABAergic and glycinergic networks, with a specific focus on the differentiation of neurons, formation of synapses, maturation of removal systems, and changes in their action. GABAergic and glycinergic neurons are derived from the same domains of the ventricular zone. Initially, GABAergic neurons are differentiated, and their axons form synapses. Some of these neurons remain GABAergic in lamina I and II. Many GABAergic neurons convert to a coreleasing state. The coreleasing neurons and terminals remain in the dorsal horn, whereas many ultimately become glycinergic in the ventral horn. During the development of terminals and the transformation from radial glia to astrocytes, GABA and glycine receptor subunit compositions markedly change, removal systems mature, and GABAergic and glycinergic action shifts from excitatory to inhibitory.

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• Specific Expression of KCC2 in the α Cells of Normal and Type 1 Diabetes Model Mouse Pancreatic Islets

  Chigusa Shimizu-Okabe, Shigeki Okada, Shiki Okamoto, Hiroaki Masuzaki, Chitoshi Takayama

  ACTA HISTOCHEMICA ET CYTOCHEMICA ( Japan Society of Histochemistry & Cytochemistry )  55 ( 1 ) 47 - 56   2022 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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• Development of the GABAergic network in the mouse spinal cord

  Shiori Kobayashi, Chigusa Shimizu-Okabe, Jeongtae Kim, Yoshinori Kosaka, Masanobu Sunagawa, Akihito Okabe, Chitoshi Takayama

  Development of the GABAergic network in the mouse spinal cord Factors Affecting Neurodevelopment - Genetics, Neurology, Behavior, and Diet - Chapter 24,     273 - 286   2021 [ Peer Review Accepted ]

  Type of publication: Research paper (other science council materials etc.)

• Development and persistence of neuropathic pain through microglial activation and KCC2 decreasing after mouse tibial nerve injury

  Kosaka Yoshinori, Yafuso Tsukasa, Shimizu-Okabe Chigusa, Kim Jeongtae, Kobayashi Shiori, Okura Nobuhiko, Ando Hironobu, Okabe Akihito, Takayama Chitoshi

  BRAIN RESEARCH   1733   146718 - 146718   2020.04 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  Gamma-amino butyric acid (GABA) is an inhibitory neurotransmitter in the mature brain, but is excitatory during development and after motor nerve injury. This difference in GABAergic action depends on the intracellular chloride ion concentration ([Cl-]i), primarily regulated by potassium chloride co-transporter 2 (KCC2). To reveal precise processes of the neuropathic pain through changes in GABAergic action, we prepared tibial nerve ligation and severance models using male mice, and examined temporal relationships amongst changes in (1) the mechanical withdrawal threshold in the sural nerve area, (2) localization of the molecules involved in GABAergic transmission and its upstream signaling in the dorsal horn, and (3) histology of the tibial nerve. In the ligation model, tibial nerve degeneration disappeared by day 56, but mechanical allodynia, reduced KCC2 localization, and increased microglia density remained until day 90. Microglia density was higher in the tibial zone than the sural zone before day 21, but this result was inverted after day 28. In contrast, in the severance model, all above changes were detected until day 28, but were simultaneously and significantly recovered by day 90. These results suggested that in male mice, allodynia may be caused by reduced GABAergic synaptic inhibition, resulting from elevated [Cl-]i after the reduction of KCC2 by activated microglia. Furthermore, our results suggested that factors from degenerating nerve terminals may diffuse into the sural zone, whereby they induced the development of allodynia in the sural nerve area, while other factors in the sural zone may mediate persistent allodynia through the same pathway.

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Other Papers 【 display / non-display 】

Other Papers 【 display / non-display 】

• TRPM7キナーゼ活性は肝臓の脂質代謝調節に関与する

  片桐 千秋, 貝塚 拓, 井上 華, 清水 千草, 小西 真人, 富澤 一仁, 高山 千利, コザック・アショット, 松下 正之

  生命科学系学会合同年次大会 ( 生命科学系学会合同年次大会運営事務局 )  2017年度   [2P - 1049]   2017.12

   

Grant-in-Aid for Scientific Research 【 display / non-display 】

Grant-in-Aid for Scientific Research 【 display / non-display 】

• Grant-in-Aid for Scientific Research(C)

  Project Year: 2023.04  -  2026.03 

• Grant-in-Aid for Scientific Research(C)

  Project Year: 2021.04  -  2024.03 

  Direct: 3,200,000 (YEN) 

• Grant-in-Aid for Scientific Research(C)

  Project Year: 2018.04  -  2022.03 

  Direct: 3,400,000 (YEN)  Overheads: 1,020,000 (YEN)  Total: 4,420,000 (YEN)

• Grant-in-Aid for Scientific Research(C)

  Project Year: 2018.04  -  2021.03 

  Direct: 3,400,000 (YEN) 

• Grant-in-Aid for JSPS Fellows

  Project Year: 2016.04  -  2019.03 

  Direct: 4,000,000 (YEN)  Overheads: 5,200,000 (YEN)  Total: 1,200,000 (YEN)

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