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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 following cranial irradiation were also relieved by treatment of allantoin and neferine. These findings demonstrate that TTR plays a critical role in neurogenesis after irradiation, and allantoin and neferine could be potential drug candidates for recovering the effects of radiation on neurogenesis and depression.

Author information

Kang J1, Kim W2,3, Seo H1, Kim E1, Son B1, Lee S1, Park G1, Jo S4, Moon C5, Youn H6, Youn B7,8.
1
Department of Integrated Biological Science, Pusan National University, Busan, 46241, Republic of Korea.
2
Department of Biological Sciences, Pusan National University, Busan, 46241, Republic of Korea.
3
Department of Biology Education, Korea National University of Education, Cheongju, 28173, Republic of Korea.
4
Department of Radiation Oncology, Haeundae Paik Hospital, Inje University School of Medicine, Busan, 48108, Republic of Korea.
5
Department of Veterinary Anatomy, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju, 61186, Republic of Korea.
6
Department of Integrative Bioscience and Biotechnology, Sejong University, Seoul, 05006, Republic of Korea. hsyoun@sejong.ac.kr.
7
Department of Integrated Biological Science, Pusan National University, Busan, 46241, Republic of Korea. bhyoun72@pusan.ac.kr.
8
Department of Biological Sciences, Pusan National University, Busan, 46241, Republic of Korea. bhyoun72@pusan.ac.kr.