AUTHOR=Abe Yuichi , Nishimura Yoshiki , Nakamura Kaori , Tamura Shigehiko , Honsho Masanori , Udo Hiroshi , Yamashita Toshihide , Fujiki Yukio 

TITLE=Peroxisome Deficiency Impairs BDNF Signaling and Memory

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=8

YEAR=2020

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.567017

DOI=10.3389/fcell.2020.567017

ISSN=2296-634X

ABSTRACT=<p>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 <italic>Pex2</italic>-knockout mouse. Peroxisome deficiency in the conditional <italic>Pex2</italic>-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.</p>