Nasal obstruction during adolescence induces memory/learning impairments associated with BDNF/TrkB signaling pathway hypofunction and high corticosterone levels

青春期鼻塞会导致与 BDNF/TrkB 信号通路功能减退和皮质酮水平升高相关的记忆/学习障碍

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作者:Takuya Ogawa, Hidemasa Okihara, Satoshi Kokai, Yasunori Abe, Uchima Koecklin Karin Harumi, Mio Makiguchi, Chiho Kato, Tadachika Yabushita, Makoto Michikawa, Takashi Ono

Abstract

The hippocampus is an important brain region involved in memory and learning. Brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB), and phospho-p44/p42 mitogen-activated protein kinase (MAPK) are known to contribute to hippocampal memory/learning. The present study aimed to clarify the effects of nasal obstruction during the growth period on memory/learning in an animal model, using combined behavioral, biochemical, and histological approaches. Male BALB/C mice underwent unilateral nasal obstruction (UNO) by cauterization at 8 days of age and were subjected to Y-maze and passive avoidance tests at 15 weeks of age. The serum corticosterone levels were measured using an enzyme-linked immunosorbent assay, and brain tissues were subjected to hematoxylin-eosin staining and histological analysis or homogenization and Western blot analysis. Compared with control mice, UNO mice had lower blood oxygen saturation levels and exhibited apparent memory/learning impairments during behavioral testing. Additionally, the UNO group had higher hippocampal BDNF levels and serum corticosterone levels, lower hippocampal TrkB and phospho-p44/p42 MAPK levels, and reduced neuron numbers relative to controls. Our findings suggest that UNO during adolescence affects the hippocampus and causes memory/learning impairments.

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