Open AccessEndothelial ErbB4 deficit induces alterations in exploratory behavior and brain energy metabolism in mice
Author(s) -
Wu Gang,
Liu XiuXiu,
Lu NanNan,
Liu QiBing,
Tian Yun,
Ye WeiFeng,
Jiang GuoJun,
Tao RongRong,
Han Feng,
Lu YingMei
Publication year - 2017
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12695
Subject(s) - erbb4 , downregulation and upregulation , neuroscience , conditional gene knockout , receptor tyrosine kinase , receptor , gas6 , knockout mouse , biology , signal transduction , microbiology and biotechnology , chemistry , endocrinology , psychology , medicine , biochemistry , phenotype , gene
Summary 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;ErbB4 f/f mice. Consistently, the immunoblot data demonstrate the downregulation of brain Glut1, phospho‐ ULK 1 (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.