1. Endothelial ErbB4 deficit induces alterations in exploratory behavior and brain energy metabolism in mice.
- Author
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Wu, Gang, Liu, Xiu‐Xiu, Lu, Nan‐Nan, Liu, Qi‐Bing, Tian, Yun, Ye, Wei‐Feng, Jiang, Guo‐Jun, Tao, Rong‐Rong, Han, Feng, and Lu, Ying‐Mei
- Subjects
PROTEIN-tyrosine kinases ,ENDOTHELIAL cells ,ENERGY metabolism ,BRAIN metabolism ,PROTEIN deficiency - Abstract
Aims The receptor tyrosine kinase ErbB4 is present throughout the primate brain and has a distinct functional profile. In this study, we investigate the potential role of endothelial ErbB4 receptor signaling in the brain. Results Here, we show that the endothelial cell-specific deletion of ErbB4 induces decreased exploratory behavior in adult mice. However, the water maze task for spatial memory and the memory reconsolidation test reveal no changes; additionally, we observe no impairment in Ca MKII phosphorylation in Cdh5Cre;ErbB4
f/f mice, which indicates that the endothelial ErbB4 deficit leads to decreased exploratory activity rather than direct memory deficits. Furthermore, decreased brain metabolism, which was measured using micro-positron emission tomography, is observed in the Cdh5Cre;ErbB4f/f mice. Consistently, the immunoblot data demonstrate the downregulation of brain Glut1, phospho- ULK1 (Ser555), and TIGAR in the endothelial ErbB4 conditional knockout mice. Collectively, our findings suggest that endothelial ErbB4 plays a critical role in regulating brain function, at least in part, through maintaining normal brain energy homeostasis. Conclusions Targeting ErbB4 or the modulation of endothelial ErbB4 signaling may represent a rational pharmacological approach to treat neurological disorders. [ABSTRACT FROM AUTHOR]- Published
- 2017
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