Ting-Ting Zhuang1, Chuan Pan1, Jing-Jing Chen1, Fei Han1, Xiu-Ling Zhu2, Hui Xu3, Ya-Ping Lu4. 1. College of Life Science, Anhui Normal University, No. 1 Beijing East Road, Wuhu 241000, China. 2. College of Life Science, Anhui Normal University, No. 1 Beijing East Road, Wuhu 241000, China; Department of Anatomy, Wannan Medical College, No. 22 Wenchang West Road, Wuhu 241002, China. 3. College of Life Science, Anhui Normal University, No. 1 Beijing East Road, Wuhu 241000, China; Anhui College of Traditional Chinese Medicine, No. 18 Wushashan West Road, Wuhu 241002, China. 4. College of Life Science, Anhui Normal University, No. 1 Beijing East Road, Wuhu 241000, China. Electronic address: yapinglu@ahnu.edu.cn.
Abstract
INTRODUCTION: Recent studies have found that persistent hypoxia caused by chronic asthma, especially during childhood, affects the development and function of the brain, but the mechanism is unclear. In the present study, BDNF and its signal pathway was investigated in mediating chronic asthma induced-neuronal changes that lead to behavior alterations. METHODS: The chronic asthma model was induced by sensitization with ovalbumin for more than 9 weeks in immature mice. Morris water maze test (MWMT), open field test (OFT) and elevated plus maze test (EPMT) were used to conduct behavioral evaluation. Neuronal morphology in hippocampal CA1, CA3 and DG was assessed using ImageJ's Sholl plugin and RESCONSTRUCT software. BDNF signaling pathway related molecules was determined by Western blotting. RESULTS: Chronic asthma does affect the behavioral performances of immature mice evaluated in MWMT, OFT, and EPMT. The analysis by three-dimensional reconstruction software found that following the behavioral alteration of asthmatic mice, dendritic changes also occurred in hippocampal neurons, including shortened dendrite length, significantly reduced number of dendritic branches, decreased density of dendritic spines, and reduced percentage of functional dendritic spine types. At the same time, by immunofluorescence and western blotting, we also found that alterations in dendritic morphology were consistent with activation of cofilin1 and changes in BDNF-Cdc42/RhoA levels. Some of the changes mentioned above can be alleviated by intranasal administration of budesonide. CONCLUSION: Our data suggest that response similar to nicotine withdrawal or/and hypoxia induced by childhood chronic asthma enhances the BDNF-Cdc42/RhoA signaling pathway and activates cofilin1, leading to the remodeling of actin, causing the loss of dendritic spines and atrophy of dendrites, eventually resulting in behavioral alterations.
INTRODUCTION: Recent studies have found that persistent hypoxia caused by chronic asthma, especially during childhood, affects the development and function of the brain, but the mechanism is unclear. In the present study, BDNF and its signal pathway was investigated in mediating chronic asthma induced-neuronal changes that lead to behavior alterations. METHODS: The chronic asthma model was induced by sensitization with ovalbumin for more than 9 weeks in immature mice. Morris water maze test (MWMT), open field test (OFT) and elevated plus maze test (EPMT) were used to conduct behavioral evaluation. Neuronal morphology in hippocampal CA1, CA3 and DG was assessed using ImageJ's Sholl plugin and RESCONSTRUCT software. BDNF signaling pathway related molecules was determined by Western blotting. RESULTS:Chronic asthma does affect the behavioral performances of immature mice evaluated in MWMT, OFT, and EPMT. The analysis by three-dimensional reconstruction software found that following the behavioral alteration of asthmatic mice, dendritic changes also occurred in hippocampal neurons, including shortened dendrite length, significantly reduced number of dendritic branches, decreased density of dendritic spines, and reduced percentage of functional dendritic spine types. At the same time, by immunofluorescence and western blotting, we also found that alterations in dendritic morphology were consistent with activation of cofilin1 and changes in BDNF-Cdc42/RhoA levels. Some of the changes mentioned above can be alleviated by intranasal administration of budesonide. CONCLUSION: Our data suggest that response similar to nicotine withdrawal or/and hypoxia induced by childhood chronic asthma enhances the BDNF-Cdc42/RhoA signaling pathway and activates cofilin1, leading to the remodeling of actin, causing the loss of dendritic spines and atrophy of dendrites, eventually resulting in behavioral alterations.
Authors: Melissa A Rosenkranz; Douglas C Dean; Barbara B Bendlin; Nizar N Jarjour; Stephane Esnault; Henrik Zetterberg; Amanda Heslegrave; Michael D Evans; Richard J Davidson; William W Busse Journal: J Allergy Clin Immunol Date: 2021-09-15 Impact factor: 10.793
Authors: Ajay Kumar Nair; Carol A Van Hulle; Barbara B Bendlin; Henrik Zetterberg; Kaj Blennow; Norbert Wild; Gwendlyn Kollmorgen; Ivonne Suridjan; William W Busse; Melissa A Rosenkranz Journal: Alzheimers Dement (N Y) Date: 2022-07-08