Endothelial ErbB4 deficit induces alterations in exploratory behavior and brain energy metabolism in mice. (18th April 2017)

• Record Type: Journal Article
• Authors: Wu, Gang; Liu, Xiu‐Xiu; Lu, Nan‐Nan; Liu, Qi‐Bing; Tian, Yun; Ye, Wei‐Feng; Jiang, Guo‐Jun; Tao, Rong‐Rong; Han, Feng; Lu, Ying‐Mei
• Is Part Of: CNS neuroscience & therapeutics. Volume 23:Number 6(2017)
• Page Start: 510
• Page End: 517
• Publication Date: 2017-04-18
• Subjects: brain metabolism -- CaMKII -- endothelial -- ErbB4 -- exploratory behavior; Neuropharmacology -- Periodicals; Central nervous system -- Diseases -- Effect of drugs on -- Periodicals; 612.8
• DOI: 10.1111/cns.12695
• Languages: English
• ISSNs: 1755-5930

Abstract

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 CaMKII 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‐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.