Altered dynamic brain activity and its association with memory decline after night shift-related sleep deprivation in nurses.

AIMS AND OBJECTIVES: To investigate, for the first time, aberrant time-varying local brain activity in nurses following night shift-related sleep deprivation (SD) and its association with memory decline. BACKGROUND: Prior studies have elucidated alterations in static local brain activity resulting from SD in the occupations outside medical profession. DESIGN: A longitudinal study followed the STROBE recommendations. METHODS: Twenty female nurses underwent resting-state functional magnetic resonance imaging and memory function assessment (by Complex Figure Test (CFT) and the California Verbal Learning Test, Second Edition (CVLT-II)) twice, once in a rested wakefulness (RW) state and another after SD. By combining the sliding-window approach and amplitude of low-frequency fluctuation (ALFF) analysis, the dynamic ALFF (dALFF) variability was calculated to reflect the characteristics of dynamic local brain activity. RESULTS: Poor performance on the CFT and CVLT-II was observed in nurses with night shift-related SD. Reduced dALFF variability was found in a set of cognition-related brain regions (including the medial/middle/superior frontal gyrus, anterior/posterior cingulate gyrus, precuneus, angular gyrus, orbitofrontal and subgenual areas, and posterior cerebellum lobe), while increased dALFF variability was observed in the somatosensory-related, visual and auditory regions. SD-related dALFF variability alterations correlated with changes in subjects' performance on the CFT and CVLT-II. CONCLUSIONS: Night shift-related SD disturbed dynamic brain activity in high cognitive regions and induced compensatory reactions in primary perceptual cortex. Identifying dALFF variability abnormalities may broaden our understanding of neural substrates underlying SD-related cognitive alterations, especially memory dysfunction. RELEVANCE TO CLINICAL PRACTICE: Night shift-related SD is as an important occupational hazard affecting brain function in nurses. The effective countermeasure addressing the adverse outcomes of SD should be advocated for nurses. PATIENT OR PUBLIC CONTRIBUTION: Patients or public were not involved in the design and implementation of the study or the analysis and interpretation of the data.

Inhibitory effects of benzoate on chiral inversion and clearance of N(G)-nitro-arginine in conscious rats.

N(G)-nitro-arginine (NNA) is known to exhibit stereoselective pharmacokinetics in which N(G)-nitro-d-arginine (d-NNA) has a faster clearance rate than N(G)-nitro-l-arginine (l-NNA) in anesthetized rats, and d-NNA undergoes unidirectional chiral inversion. It was postulated that chiral inversion of d-NNA was performed in a two-step pathway by d-amino acid oxidase (DAAO) followed by an unidentified transaminase. Such chiral inversion contributes (at least partially) to the pharmacokinetic stereoselectivity of NNA. This study used the selective inhibitor of DAAO, sodium benzoate, to test the above hypothesis. An i.v. bolus injection of d-NNA (32 mg/kg) and l-NNA (16 mg/kg) in conscious rats exhibited biphasic disposition with different pharmacokinetic parameters in a stereospecific manner (approximately 5-10-fold differences). Unidirectional chiral inversion of d-NNA but not l-NNA was found from these animals. In addition to its similar inhibitory effects on the d-NNA conversion and DAAO activity in kidney homogenates, sodium benzoate completely blocked chiral inversion of d-NNA and led to a smaller stereospecific difference, reflected by a nearly 50% reduction of d-NNA clearance and a 2-fold increase in t(1/2) and area under the curve of d-NNA in benzoate-pretreated rats. The results suggest that DAAO plays an essential role in chiral inversion of d-NNA and chiral inversion contributes mostly to the pharmacokinetic stereospecificity of NNA.