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

Abe, Yuichi; Honsho, Masanori; Itoh, Roichi; Kawaguchi, Ryoko; Fujitani, Masashi; Fujiwara, Kazushirou; Hirokane, Masaaki; Matsuzaki, Takashi; Nakayama, Keiko; Ohgi, Ryohei; Marutani, Toshihiro; Nakayama, Keiichi I.; Yamashita, Toshio; Fujiki, Yukio

doi:10.26508/lsa.201800062

Cited by 20 publications

(27 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pex14 Δ C /Δ C mouse on a C57BL/6 background was previously described ( Abe et al, 2018 ). Heterozygous offspring ( Pex14 +/Δ C ) were intercrossed to produce homozygous mutant animals.…”

Section: Methodsmentioning

confidence: 99%

“…Patients with Zellweger syndrome (ZS), the most severe PBDs, display malformation of central nervous system (CNS) such as disturbance of cortical laminar structure, dysmorphology of Purkinje cells, and dysplasia of inferior olivary nucleus ( Volpe and Adams, 1972 ; de León et al, 1977 ; Evrard et al, 1978 ; Steinberg et al, 2006 ). To date, several Pex gene-defective ZS model mice have been generated, showing abnormal development of CNS as observed in ZS patients ( Baes et al, 1997 ; Faust and Hatten, 1997 ; Maxwell et al, 2003 ; Abe et al, 2018 ). Using these ZS model mice, pathological mechanisms underlying PBDs have been studied.…”

Section: Introductionmentioning

confidence: 99%

“…Using these ZS model mice, pathological mechanisms underlying PBDs have been studied. We recently reported that Pex14 Δ C /Δ C mouse, a ZS model mouse, upregulates brain-derived neurotrophic factor (BDNF) in the inferior olivary nucleus and elevates an inactive truncated form of its receptor, TrkB-T1, in cerebellum ( Abe et al, 2018 ). A combination of the elevated BDNF and the prominent expression of TrkB-T1 in the Pex14 Δ C /Δ C mouse gives rise to abnormal morphogenesis of Purkinje cells ( Abe et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

“…We recently reported that Pex14 Δ C /Δ C mouse, a ZS model mouse, upregulates brain-derived neurotrophic factor (BDNF) in the inferior olivary nucleus and elevates an inactive truncated form of its receptor, TrkB-T1, in cerebellum ( Abe et al, 2018 ). A combination of the elevated BDNF and the prominent expression of TrkB-T1 in the Pex14 Δ C /Δ C mouse gives rise to abnormal morphogenesis of Purkinje cells ( Abe et al, 2018 ). We also showed that cytosolically mislocalized catalase in peroxisome-deficient cells induces the cytosolic reductive state, resulting in the elevation of BDNF ( Abe et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…A number of studies reported that BDNF-TrkB signaling in the adult brain is involved in various neural functions such as synaptic plasticity, memory, and neurogenesis ( Park and Poo, 2013 ). Peroxisome deficiency attenuates BDNF signaling, resulting in the malformation of neonatal cerebellum of Pex14 Δ C /Δ C mouse at early stages after birth ( Abe et al, 2018 ). In the present study, as a step to investigating the peroxisomal functions in adulthood, we generated tamoxifen-inducible conditional Pex2 -knockout mouse.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Peroxisome Deficiency Impairs BDNF Signaling and Memory

Abe

Nishimura

Nakamura

et al. 2020

Front. Cell Dev. Biol.

Self Cite

View full text Add to dashboard Cite

Peroxisome is an intracellular organelle that functions in essential metabolic pathways including β-oxidation of very-long-chain fatty acids and biosynthesis of plasmalogens. Peroxisome biogenesis disorders (PBDs) manifest severe dysfunction in multiple organs including central nervous system (CNS), whilst the pathogenic mechanisms are largely unknown. We recently reported that peroxisome-deficient neural cells secrete an increased level of brain-derived neurotrophic factor (BDNF), resulting in the cerebellar malformation. Peroxisomal functions in adulthood brain have been little investigated. To induce the peroxisome deficiency in adulthood brain, we here established tamoxifen-inducible conditional Pex2 -knockout mouse. Peroxisome deficiency in the conditional Pex2 -knockout adult mouse brain induces the upregulated expression of BDNF and its inactive receptor TrkB-T1 in hippocampus, which notably results in memory disturbance. Our results suggest that peroxisome deficiency gives rise to the dysfunction of hippocampal circuit via the impaired BDNF signaling.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Peroxisome Deficiency Impairs BDNF Signaling and Memory

Abe

Nishimura

Nakamura

et al. 2020

Front. Cell Dev. Biol.

Self Cite

View full text Add to dashboard Cite

show abstract

Genetic defects in peroxisome morphogenesis (Pex11β, dynamin‐like protein 1, and nucleoside diphosphate kinase 3) affect docosahexaenoic acid‐phospholipid metabolism

Abe

Wanders

Waterham

et al. 2022

J of Inher Metab Disea

Self Cite

View full text Add to dashboard Cite

Peroxisomes are essential organelles involved in lipid metabolisms including plasmalogen biosynthesis and β-oxidation of very long-chain fatty acids. Peroxisomes proliferate by the growth and division of pre-existing peroxisomes. The peroxisomal membrane is elongated by Pex11β and then divided by the dynamin-like GTPase, DLP1 (also known as DRP1 encoded by DNM1L gene), which also functions as a fission factor for mitochondria. Nucleoside diphosphate kinase 3 (NME3) localized in both peroxisomes and mitochondria generates GTP for DLP1 activity. Deficiencies of either of these factors induce abnormal morphology of peroxisomes and/or mitochondria, and are associated with central nervous system dysfunction. To investigate whether the impaired division of peroxisomes affects lipid metabolisms, we assessed the phospholipid composition of cells lacking each of the different division factors. In fibroblasts from the patients deficient in DLP1, NME3, or Pex11β, docosahexaenoic acid (DHA, C22:6)containing phospholipids were found to be decreased. Conversely, the levels of several fatty acids such as arachidonic acid (AA, C20:4) and oleic acid (C18:1) were elevated. Mouse embryonic fibroblasts from Drp1and Pex11β-knockout mice also showed a decrease in the levels of phospholipids containing DHA and AA. Collectively, these results suggest that the dynamics of organelle morphology exert marked effects on the fatty acid composition of phospholipids.

show abstract

Mouse Models to Study Peroxisomal Functions and Disorders: Overview, Caveats, and Recommendations

Kocherlakota¹,

Swinkels²,

Veldhoven³

et al. 2023

Methods in Molecular Biology

View full text Add to dashboard Cite

During the last three decades many mouse lines were created or identified that are deficient in one or more peroxisomal functions. Different methodologies were applied to obtain global, hypomorph, cell type selective, inducible and knockin mice. Whereas some models closely mimic pathologies in patients, others strongly deviate or no human counterpart has been reported. Often, mice, apparently endowed with a stronger transcriptional adaptation, have to be challenged with dietary additions or restrictions in order to trigger phenotypic changes. Depending on the inactivated peroxisomal protein, several approaches can be taken to validate the loss-of-function. Here, an overview is given of the available mouse models and their most important characteristics.

show abstract

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

Abstract: Peroxisome biogenesis deficiency leads to increased expression of BDNF and of a truncated form of the BDNF receptor in the cerebellum, attenuates BDNF-TrkB signaling, and results in malformation of the cerebellum.

Cited by 20 publications

References 74 publications

Peroxisome Deficiency Impairs BDNF Signaling and Memory

Peroxisome Deficiency Impairs BDNF Signaling and Memory

Genetic defects in peroxisome morphogenesis (Pex11β, dynamin‐like protein 1, and nucleoside diphosphate kinase 3) affect docosahexaenoic acid‐phospholipid metabolism

Mouse Models to Study Peroxisomal Functions and Disorders: Overview, Caveats, and Recommendations

Contact Info

Product

Resources

About