| First Author | Wu G | Year | 2017 |
| Journal | CNS Neurosci Ther | Volume | 23 |
| Issue | 6 | Pages | 510-517 |
| PubMed ID | 28421673 | Mgi Jnum | J:273760 |
| Mgi Id | MGI:6282491 | Doi | 10.1111/cns.12695 |
| Citation | Wu G, et al. (2017) Endothelial ErbB4 deficit induces alterations in exploratory behavior and brain energy metabolism in mice. CNS Neurosci Ther 23(6):510-517 |
| abstractText | 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. |
