Nasal obstruction during the growth period modulates the Wnt/β-catenin pathway and brain-derived neurotrophic factor production in association with tyrosine kinase receptor B mRNA reduction in mouse hippocampus

生长期鼻塞调节 Wnt/β-catenin 通路和脑源性神经营养因子的产生,并与小鼠海马酪氨酸激酶受体 B mRNA 减少有关

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作者:Hideyuki Ishidori, Hidemasa Okihara, Takuya Ogawa, Yasunori Abe, Chiho Kato, Phyo Thura Aung, Akiyo Fujita, Satoshi Kokai, Takashi Ono

Abstract

There is accumulating evidence that nasal obstruction induces high-level brain dysfunction, including memory and learning deficits. We previously demonstrated that unilateral nasal obstruction (UNO) during the growth period increases the expression of brain-derived neurotrophic factor (BDNF). The expression of BDNF is regulated by the Wnt/β-Catenin pathway, which is linked to neuronal differentiation, proliferation, and maintenance. However, little is known about whether Wnt3a protein expression could be an index for modulations analyses in the Wnt/β-Catenin pathway caused by UNO during the growth period. This study aimed to investigate the effects of UNO during the growth period on the Wnt/β-Catenin pathway in the hippocampus using combined behavioural, biochemical, and histological approaches. Male BALB/C mice were randomly divided into the control (CONT; n = 6) and experimental (UNO; n = 6) groups. Blood oxygen saturation (SpO2 ) levels were measured, and a passive avoidance test was performed in mice aged 15 weeks. Brain tissues were subjected to immunohistochemistry, real-time reverse transcription-polymerase chain reaction, and western blot analysis. Compared with control mice, UNO mice had lower SpO2 levels and exhibited memory/learning impairments during behavioural testing. Moreover, Wnt3a protein, BDNF mRNA, and tyrosine kinase receptor B (TrkB) mRNA expression levels were significantly lower in the hippocampus in the UNO group than in the CONT group. Our findings suggested that UNO during the growth period appeared to modulate the hippocampal Wnt/β-catenin pathway and BDNF production in association with TrkB mRNA reduction, thereby resulting in memory and learning impairments.

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