Altered neurovascular coupling and brain arginine metabolism in endothelial nitric oxide synthase deficient mice

Publication date: Available online 13 March 2019Source: Nitric OxideAuthor(s): Ashwini Hariharan, Yu Jing, Nicola D. Collie, Hu Zhang, Ping LiuAbstractNitric oxide (NO) produced by endothelial NO synthase (eNOS) is a key regulator of cerebral blood flow (CBF) dynamics. Mice with eNOS deficiency (eNOS−/-) display age-related increases in amyloid beta in the brain and memory deficits, implicating eNOS dysfunction in the neuropathogenesis and/or development of Alzheimer's disease (AD). The present study systematically investigated behavioural, CBF and brain arginine metabolic profile changes in male and female wildtype (WT) and eNOS−/- mice at 14 months of age. eNOS−/- mice displayed altered behaviour in the Y-maze and open field tests. A real-time microcirculation imager revealed a significant sex difference in the basal CBF and significantly increased perfusion response to whisker stimulations in the Barrel cortex in both male and female eNOS−/- mice relative to their sex-matched WT controls. The treatment of 7-nitroindazole blocked the increased perfusion response to whisker stimulations in eNOS−/- mice. Neurochemically, the most intriguing changes were markedly reduced glutamine levels in both male and female eNOS−/- mice in the fontal cortex, hippocampus, parahippocampal region and cerebellum. These findings demonstrate altered behavioural function, neurovascular coupling and brain arginine metabolism (glutamine in particular) under the condition of eNOS deficie...

Source: Nitric Oxide - March 13, 2019 Category: Chemistry Source Type: research