Peroxisome biogenesis deficiency attenuates the BDNF-TrkB pathway-mediated development of the cerebellum

Yuichi Abe, Masanori Honsho, Ryota Itoh, Ryoko Kawaguchi, Masashi Fujitani, Kazushirou Fujiwara, Masaaki Hirokane, Takashi Matsuzaki, Keiko Nakayama, Ryohei Ohgi, Toshihiro Marutani, Keiichi Nakayama, Toshihide Yamashita, Yukio Fujiki

研究成果: ジャーナルへの寄稿記事

1 引用 (Scopus)

抄録

Peroxisome biogenesis disorders (PBDs) manifest as neurological deficits in the central nervous system, including neuronal migration defects and abnormal cerebellum development. However, the mechanisms underlying pathogenesis remain enigmatic. Here, to investigate how peroxisome deficiency causes neurological defects of PBDs, we established a new PBD model mouse defective in peroxisome assembly factor Pex14p, termed Pex14ΔC/ΔC mouse. Pex14ΔC/ΔC mouse manifests a severe symptom such as disorganization of cortical laminar structure and dies shortly after birth, although peroxisomal biogenesis and metabolism are partially defective. The Pex14ΔC/ΔC mouse also shows malformation of the cerebellum including the impaired dendritic development of Purkinje cells. Moreover, extracellular signal-regulated kinase and AKT signaling are attenuated in this mutant mouse by an elevated level of brain-derived neurotrophic factor (BDNF) together with the enhanced expression of TrkB-T1, a dominant-negative isoform of the BDNF receptor. Our results suggest that dysregulation of the BDNF-TrkB pathway, an essential signaling for cerebellar morphogenesis, gives rise to the pathogenesis of the cerebellum in PBDs.

元の言語英語
ジャーナルLife Science Alliance
1
発行部数6
DOI
出版物ステータス出版済み - 1 1 2018

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neurotrophins
Peroxisomes
Brain-Derived Neurotrophic Factor
cerebellum
peroxisomes
Cerebellum
brain
trkB Receptor
Defects
defect
Extracellular Signal-Regulated MAP Kinases
Neurology
Metabolism
Protein Isoforms
morphogenesis
mice
nervous system
pathogenesis
metabolism
Purkinje Cells

All Science Journal Classification (ASJC) codes

  • Ecology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Plant Science
  • Health, Toxicology and Mutagenesis

これを引用

Peroxisome biogenesis deficiency attenuates the BDNF-TrkB pathway-mediated development of the cerebellum. / Abe, Yuichi; Honsho, Masanori; Itoh, Ryota; Kawaguchi, Ryoko; Fujitani, Masashi; Fujiwara, Kazushirou; Hirokane, Masaaki; Matsuzaki, Takashi; Nakayama, Keiko; Ohgi, Ryohei; Marutani, Toshihiro; Nakayama, Keiichi; Yamashita, Toshihide; Fujiki, Yukio.

:: Life Science Alliance, 巻 1, 番号 6, 01.01.2018.

研究成果: ジャーナルへの寄稿記事

Abe, Y, Honsho, M, Itoh, R, Kawaguchi, R, Fujitani, M, Fujiwara, K, Hirokane, M, Matsuzaki, T, Nakayama, K, Ohgi, R, Marutani, T, Nakayama, K, Yamashita, T & Fujiki, Y 2018, 'Peroxisome biogenesis deficiency attenuates the BDNF-TrkB pathway-mediated development of the cerebellum', Life Science Alliance, 巻. 1, 番号 6. https://doi.org/10.26508/lsa.201800062
Abe, Yuichi ; Honsho, Masanori ; Itoh, Ryota ; Kawaguchi, Ryoko ; Fujitani, Masashi ; Fujiwara, Kazushirou ; Hirokane, Masaaki ; Matsuzaki, Takashi ; Nakayama, Keiko ; Ohgi, Ryohei ; Marutani, Toshihiro ; Nakayama, Keiichi ; Yamashita, Toshihide ; Fujiki, Yukio. / Peroxisome biogenesis deficiency attenuates the BDNF-TrkB pathway-mediated development of the cerebellum. :: Life Science Alliance. 2018 ; 巻 1, 番号 6.
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AU - Abe, Yuichi

AU - Honsho, Masanori

AU - Itoh, Ryota

AU - Kawaguchi, Ryoko

AU - Fujitani, Masashi

AU - Fujiwara, Kazushirou

AU - Hirokane, Masaaki

AU - Matsuzaki, Takashi

AU - Nakayama, Keiko

AU - Ohgi, Ryohei

AU - Marutani, Toshihiro

AU - Nakayama, Keiichi

AU - Yamashita, Toshihide

AU - Fujiki, Yukio

PY - 2018/1/1

Y1 - 2018/1/1

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AB - Peroxisome biogenesis disorders (PBDs) manifest as neurological deficits in the central nervous system, including neuronal migration defects and abnormal cerebellum development. However, the mechanisms underlying pathogenesis remain enigmatic. Here, to investigate how peroxisome deficiency causes neurological defects of PBDs, we established a new PBD model mouse defective in peroxisome assembly factor Pex14p, termed Pex14ΔC/ΔC mouse. Pex14ΔC/ΔC mouse manifests a severe symptom such as disorganization of cortical laminar structure and dies shortly after birth, although peroxisomal biogenesis and metabolism are partially defective. The Pex14ΔC/ΔC mouse also shows malformation of the cerebellum including the impaired dendritic development of Purkinje cells. Moreover, extracellular signal-regulated kinase and AKT signaling are attenuated in this mutant mouse by an elevated level of brain-derived neurotrophic factor (BDNF) together with the enhanced expression of TrkB-T1, a dominant-negative isoform of the BDNF receptor. Our results suggest that dysregulation of the BDNF-TrkB pathway, an essential signaling for cerebellar morphogenesis, gives rise to the pathogenesis of the cerebellum in PBDs.

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