Role of endothelial receptor-tyrosine kinase ErbB4 in regulating brain function

OBJECTIVE The receptor-tyrosine kinase ErbB4 is present throughout the primate brain and has a distinct functional profile.In the present study,we investigate the potential role of endothelial ErbB4 receptor signaling in the brain. METHODS ErbB4 conditional KO mice were generated by a lox P/Cre strategy. The experimenter conducting the experimentsand scoring the behavior was blinded to the genotype of the mice. Open field test,Y-maze and novel-object exploration test,novel object recognition task,step-through passive avoidance task,Morris water maze and memory reconsolidation task were carried out in WT and Cdh5-Cre; ErbB4^(loxP/loxP)mice. A high-resolution micro PET/CT scanner was used for brain metabolism imaging. RESULTS Here,we show that Cdh5Cre; ErbB4^(f/f) mice have lower levels ofexploration activity as measured by these particular behavior tests. However,our data indicate that conditional knockout of ErbB4 in endothelial cells did not impair working memory,memory acquisition,retrieval,and reconsolidation in mice. Furthermore,^(18)F-FDG-uptake was reduced in the Cdh5Cre; ErbB4^(f/f) mice as revealed by the significantly decreased SUVs in compared with the WT mice. Consistently,the immunoblot data demonstrate the downregulation of brain Glut1,phosphoULK1(Ser555) and TIGAR in the endothelial ErbB4 conditional knockout mice. Collectively,the endothelial ErbB4 deletion induced impairment in exploratory activity in adult mice,which may be due to the decreased brain energy metabolism. CONCLUSION Our study provides insight into the potential pathophysiological mechanisms of endothelial ErbB 4 and therapeutic strategies for neurological disorders.

Evaluation of the anxiolytic effect of the methanol stem extracts of Cissus quadrangularis

Objective:To investigate the potentials of the stem of Cissus quadrangularis(C.quadrangularis)in the control of anxiety and related motor coordination effects in mice using experimental models.Methods:The methanol extract of the stem of C.quadrangularis was studied in mice using elevated plus maze,hole board,open field and stair case tests.Acute toxicity and phytochemical analysis were also carried out.Results:The methanol extract(100,200,300 and 400 mg/kg)exhibited significant anxiolytic effects,as evident by significant(P<0.05)increase in the number of crossings at 100,200 and 300 mg/kg dose and number of rearing at 200,300 and 400 mg/kg dose in open field behavior test.Time spent in the open arms and number of entrances in the open arms increased significantly(P<0.05,P<0.01)at the dose of 200 and 300 mg/kg in elevated plus maze test.Post hoc analysis showed that C.quadrangularis at the dose of 200 and 300 mg/kg significantly(P<0.05)increased the number of steps taken and number of head dips.Significant(P<0.05)reduction in time duration on the bar and number of rearing were observed at the dose of 200,300 and 400 mg/kg.The acute toxicity test revealed an oral LD_(50)above 5000 mg/kg,while phytochemical studies showed the presence of phytosterols,terpenoids,saponins,flavanoids,tannins,carbohydrates and aminoacids.Conclusions:The stem extracts of C.quadrangularis is anxiolytic in nature,which contribute to its use in traditional medicine as anxiolytic.