Radiation-induced overexpression of transthyretin inhibits retinol-mediated hippocampal neurogenesis

Scientific Reports
JiHoon KangBuHyun Youn

Abstract

Cranial irradiation is the main therapeutic strategy for treating primary and metastatic brain tumors. However, radiation is well-known to induce several unexpected side effects including emotional disorders. Although radiation-induced depression may cause decreased quality of life after radiotherapy, investigations of its molecular mechanism and therapeutic strategies are still insufficient. In this study, we found that behavioral symptoms of depression on mice models with the decrease of BrdU/NeuN- and Dcx-positive populations and MAP-2 expression in hippocampus were induced by cranial irradiation, and transthyretin (TTR) was highly expressed in hippocampus after irradiation. It was shown that overexpression of TTR resulted in the inhibition of retinol-mediated neuritogenesis. PAK1 phosphorylation and MAP-2 expression were significantly reduced by TTR overexpression following irradiation. Moreover, we observed that treatment of allantoin and neferine, the active components of Nelumbo nucifera, interrupted irradiation-induced TTR overexpression, consequently leading to the increase of PAK1 phosphorylation, neurite extension, BrdU/NeuN- and Dcx-positive populations, and MAP-2 expression. Behavioral symptoms of depression follow...Continue Reading

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Citations

Aug 23, 2019·Nature Communications·Chiara MariottiniRavi Iyengar
Sep 10, 2019·International Journal of Radiation Biology·Beomseok SonBuHyun Youn
Sep 22, 2020·Journal of Neuroinflammation·Lindsay A HohsfieldKim N Green
Aug 10, 2020·Experimental Cell Research·Christoph NiemietzAndree Zibert
Jun 25, 2021·Human & Experimental Toxicology·Y-F Gu, L-T Kong

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Datasets Mentioned

BETA
GSE94440

Methods Mentioned

BETA
ELISA
transfection
electrophoresis
PCR
Chip
Assay
chips
protein assay

Software Mentioned

Affymetrix Command Console
DAVID ( Database for Annotation , Visualization , and Integrat...
Affymetrix Expression Console
ImageJ
Scion Image
R
MEV ( Multi Experiment Viewer )
Fiji
Prism

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