Biology subjects

Wright, C. J.

Publications and source records attributed to Wright, C. J..

2 recordsLinked to original sources

bioRxiv2022

Kynurenine aminotransferase II inhibition promotes sleep and rescues impairments induced by neurodevelopmental insult

Dysregulated sleep is commonly reported in individuals with neuropsychiatric disorders, including schizophrenia (SCZ) and bipolar disorder (BPD). Physiology and pathogenesis of these disorders points to aberrant metabolism, during neurodevelopment and adulthood, of tryptophan via the kynurenine pathway (KP). Kynurenic acid (KYNA), a neuroactive KP metabolite derived from its precursor kynurenine by kynurenine aminotransferase II (KAT II), is increased in the brains of individuals with SCZ and BPD. We hypothesize that elevated KYNA, an inhibitor of glutamatergic and cholinergic neurotransmission, contributes to sleep dysfunction. Employing the embryonic kynurenine (EKyn) paradigm to elevate KYNA in the fetal brain, we presently examined whether reducing KYNA in adulthood by pharmacologically inhibiting KAT II would improve sleep quality. Pregnant Wistar rats were fed either kynurenine (100 mg/day) (EKyn) or control wet mash (ECon) from embryonic day (ED) 15 to ED 22. In adulthood, male and female offspring were implanted with devices to record electroencephalogram (EEG) and electromyogram (EMG) telemetrically for continuous sleep-wake data acquisition. Each subject was treated with either vehicle or PF-04859989 (30 mg/kg, s.c.), an irreversible KAT II inhibitor, at zeitgeber time (ZT) 0 or ZT 12. KAT II inhibitor improved sleep architecture maintaining entrainment of the light-dark cycle; ZT 0 treatment with PF-04859989 induced transient improvements in rapid eye movement (REM) and non-REM (NREM) during the immediate light phase, while the impact of ZT 12 treatment was delayed until the subsequent light phase. PF-04859989 administration at ZT 0 enhanced NREM delta spectral power and reduced activity and body temperature. In conclusion, reducing de novo KYNA production alleviated sleep disturbances and increased sleep quality in EKyn, while also improving sleep outcomes in ECon offspring. Our findings place attention on KAT II inhibition as a novel mechanistic approach to treating disrupted sleep behavior with potential translational implications for patients with neurodevelopmental and neuropsychiatric disorders.

neuroscience↗

bioRxiv2020

One Health, One Hive: A scoping review of honey bees, climate change, pollutants, and antimicrobial resistance

Anthropogenic climate change and increasing antimicrobial resistance (AMR) together threaten the last 50 years of public health gains. Honey bees are a model One Health organism to investigate interactions between climate change and AMR. The objective of this scoping review was to examine the range, extent, and nature of published literature on the relationship between AMR and honey bees in the context of climate change and environmental pollutants. The review followed systematic search methods and reporting guidelines. A protocol was developed a priori in consultation with a research librarian. Resulting Boolean search strings were used to search Embase(R) via Ovid(R), MEDLINE(R), Scopus(R), AGRICOLA and Web of Science databases. Two independent reviewers conducted two-stage screening on retrieved articles. To be included, the article had to examine honey bees, AMR, and either climate change or environmental pollution. Data, in accordance with Joanna Briggs Institute guidelines, were extracted from relevant articles and descriptively synthesized in tables, figures, and narrative form. A total of 21 articles met the inclusion criteria, with almost half of all articles being published in the last five years (n=10). These articles predominantly investigated hive immunocompetence and multi-drug resistance transporter downregulation (n=10), susceptibility to pests (n=15), especially American foul brood (n=9), and hive product augmentation (n=3). This review identified key themes and gaps in the literature, including the need for future interdisciplinary research to explore the link between AMR and environmental change evidence streams in honey bees. We identified three potential linkages between pollutive and climatic factors and risk of AMR. These interconnections reaffirm the necessity of a One Health framework to tackle global threats and investigate complex issues that extend beyond honey bee research into the public health sector. It is integral that we view these "wicked" problems through an interdisciplinary lens to explore long-term strategies for change.

ecology↗