Journal
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
Volume 87, Issue -, Pages 60-72Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.niox.2019.03.006
Keywords
eNOS deficiency; Cerebral blood flow; Neurovascular coupling; Nitric oxide; Arginine metabolism; Glutamine
Categories
Funding
- Health Research Council of New Zealand [16/597]
- New Zealand Lottery Health Research [R-LHR-2016-27043]
- University of Otago Research Grant
- Department of Anatomy, University of Otago, New Zealand
- Hercus Taieri Resource Unit, University of Otago, New Zealand
- University of Otago
Ask authors/readers for more resources
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 and brain arginine metabolism (glutamine in particular) under the condition of eNOS deficiency, which further supports the role of eNOS dysfunction in the AD neuropathogenesis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available