Riddle, A. | bioRxiv Science

bioRxiv2024

Mild neonatal hypoxia disrupts adult hippocampal learning and memory and is associated with CK2-mediated dysregulation of synaptic calcium-activated potassium channel KCNN2

ObjectiveAlthough nearly half of preterm survivors display persistent neurobehavioral dysfunction including memory impairment without overt gray matter injury, the underlying mechanisms of neuronal or glial dysfunction, and their relationship to commonly observed cerebral white matter injury are unclear. We developed a mouse model to test the hypothesis that mild hypoxia during preterm equivalence is sufficient to persistently disrupt hippocampal neuronal maturation related to adult cellular mechanisms of learning and memory. Methods: Neonatal (P2) mice were exposed to mild hypoxia (8%O2) for 30 min and evaluated for acute injury responses or survived until adulthood for assessment of learning and memory and hippocampal neurodevelopment. ResultsNeonatal mild hypoxia resulted in clinically relevant oxygen desaturation and tachycardia without bradycardia and was not accompanied by cerebral gray or white matter injury. Neonatal hypoxia exposure was sufficient to cause hippocampal learning and memory deficits and abnormal maturation of CA1 neurons that persisted into adulthood. This was accompanied by reduced hippocampal CA3-CA1 synaptic strength and LTP and reduced synaptic activity of calcium-sensitive SK2 channels, key regulators of spike timing dependent neuroplasticity, including LTP. Structural illumination microscopy revealed reduced synaptic density, but intact SK2 localization at the synapse. Persistent loss of SK2 activity was mediated by altered casein kinase 2 (CK2) signaling. InterpretationClinically relevant mild hypoxic exposure in the neonatal mouse is sufficient to produce morphometric and functional disturbances in hippocampal neuronal maturation independently of white matter injury. Additionally, we describe a novel persistent mechanism of potassium channel dysregulation after neonatal hypoxia. Collectively our findings suggest an unexplored explanation for the broad spectrum of neurobehavioral, cognitive and learning disabilities that paradoxically persist into adulthood without overt gray matter injury after preterm birth.

neuroscience↗

bioRxiv2020

High Real-time Reporting of Domestic and Wild Animal Diseases Following Rollout of Mobile Phone Reporting System in Kenya

BackgroundTo improve early detection of emerging infectious diseases in sub-Saharan Africa (SSA), many of them zoonotic, numerous electronic animal disease-reporting systems have been piloted but not implemented because of cost, lack of user friendliness, and data insecurity. In Kenya, we developed and rolled out an open-source mobile phone-based domestic and wild animal disease reporting system and collected data over two years to demonstrate its robustness and ability to track disease trends. MethodsThe Kenya Animal Biosurveillance System (KABS) application was built on the Java(R) platform, freely downloadable for android compatible mobile phones, and supported by web-based account management, form editing and data monitoring. The application was integrated into the surveillance systems of Kenyas domestic and wild animal sectors by adopting their existing data collection tools, and targeting disease syndromes prioritized by national, regional and international animal and human health agencies. Smartphone-owning government and private domestic and wild animal health officers were recruited and trained on the application, and reports received and analyzed by Kenya Directorate of Veterinary Services. The KABS application performed automatic basic analyses (frequencies, spatial distribution), which were immediately relayed to reporting officers as feedback. ResultsOver 95% of trained domestic animal officers downloaded the application, and >72% of them started reporting using the application within three months. Introduction of the application resulted in 2- to 10-fold increase in number of disease reports when compared the previous year (p<0.05), and reports were more spatially distributed. Among domestic animals, food animals (cattle, sheep, goats, camels, and chicken) accounted for >90% of the reports, with respiratory, gastrointestinal and skin diseases constituting >85% of the reports. Herbivore wildlife (zebra, buffalo, elephant, giraffe, antelopes) accounted for >60% of the wildlife disease reports, followed by carnivores (lions, cheetah, hyenas, jackals, and wild dogs). Deaths, traumatic injuries, and skin diseases were most reported in wildlife. ConclusionsThis open-source system was user friendly and secure, ideal for rolling out in other countries in SSA to improve disease reporting and enhance preparedness for epidemics of zoonotic diseases. Authors SummaryTaking advantage of a recently developed freely downloadable disease reporting application in the United States, we customized it for android smartphones to collect and submit domestic and wild animal disease data in real-time in Kenya. To enhance user friendliness, the Kenya Animal Biosurveillance System (KABS) was installed with disease reporting tools currently used by the animal sector and tailored to collected data on transboundary animal disease important for detecting zoonotic endemic and emerging diseases. The KABS database was housed by the government of Kenya, providing important assurance on its security. The application had a feedback module that performed basics analysis to provide feedback to the end-user in real-time. Rolling out of KABS resulted in >70% of domestic and wildlife disease surveillance officers using it to report, resulting in exponential increase in frequency and spatial distributions of reports regions. Utility of the system was demonstrated by successful detected a Rift Valley fever outbreak in livestock in 2018, resulting in early response and prevention of widespread human infections. For the wildlife sector in Eastern Africa, the application provided the first disease surveillance system developed. This open-source system is ideal for rolling out in other countries in sub-Saharan Africa to improve disease reporting and enhance preparedness for epidemics of zoonotic diseases.

microbiology↗