Mar 17, 2019

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

Nitric Oxide : Biology and Chemistry
Ashwini HariharanPing Liu

Abstract

Nitric 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 frontal cortex, hippocampus, parahippocampal region and cerebellum. These findings demonstrate altered behavioural function, neurovascular coupling ...Continue Reading

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Mentioned in this Paper

Indazoles
Arginine hydrochloride
Study
Familial Alzheimer Disease (FAD)
Visual Field Study
Memory Impairment
Brain
Nos1 protein, mouse
Alzheimer's Disease
Blood Flow

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