TY - JOUR T1 - Peroxisome biogenesis deficiency attenuates the BDNF-TrkB pathway-mediated development of the cerebellum JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201800062 VL - 1 IS - 6 SP - e201800062 AU - Yuichi Abe AU - Masanori Honsho AU - Ryota Itoh AU - Ryoko Kawaguchi AU - Masashi Fujitani AU - Kazushirou Fujiwara AU - Masaaki Hirokane AU - Takashi Matsuzaki AU - Keiko Nakayama AU - Ryohei Ohgi AU - Toshihiro Marutani AU - Keiichi I Nakayama AU - Toshihide Yamashita AU - Yukio Fujiki Y1 - 2018/12/01 UR - https://www.life-science-alliance.org/content/1/6/e201800062.abstract N2 - 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. ER -