2022-12-292022-12-292017-01-20Gören, B. vd. (2017). ''Long-term cognitive effects of uridine treatment in a neonatal rat model of hypoxic-ischemic encephalopathy''. Brain Research, 1659, 81-87.0006-8993https://doi.org/10.1016/j.brainres.2017.01.026https://www.sciencedirect.com/science/article/pii/S00068993173004091872-6240http://hdl.handle.net/11452/30159Hypoxic-ischemic encephalopathy (HIE), is the most common brain disorder in neonates during the perinatal period, which, to date, can only be managed to some extent by hypothermia. Uridine is the principal circulating pyrimidine in humans which is utilized as a precursor for membrane phospholipid biosynthesis. Uridine has recently been shown to provide clinical benefit in treatment of Alzheimer's disease due to its involvement in increasing number of brain synapses along with other phospholipid precursors. We previously showed that uridine treatment ameliorated brain damage by reducing apoptosis in a rat model of neonatal HIE. The aim of the present study was to investigate the effects of uridine administration on cognitive functions during periadolescent period in rats subjected to hypoxic-ischemic (HI) brain damage in neonatal period. Male newborn rats were subjected to HI insult on postnatal day 7 (P7) and were injected intraperitoneally with either saline or uridine (500 mg/kg) for three consecutive days. Part of pups in each group were sacrificed on P10 to collect brain samples for active Caspase-3 analyses and the remaining pups were raised through P40 to evaluate early reflexes, sensorimotor coordination and learning and memory functions by Negative Geotaxis (NG), Beam Walking (BW) and Morris Water Maze (MWM) tasks, respectively. Confirming our previous findings, we showed that uridine administration reduced apoptotic cell damage on P10. No significant difference was observed between uridine and saline groups in early reflexes or sensorimotor coordination. On the other hand, rats receiving uridine displayed improved learning and memory in MWM during periadolescent period. We conclude that uridine treatment improves learning and memory in the long term by, probably, reducing apoptotic cell death in early newborn period. This is the first study to show beneficial cognitive effects of uridine in rats with brain damage.eninfo:eu-repo/semantics/closedAccessNeurosciences & neurologyBehaviorHypoxic-ischemicEncephalopathyLearning and memoryNeonatal ratUridineBrain-injuryWater-mazeBehavioral deficitsImpoverished ratsMagnesium-sulfateAnimal-modelProtectsMemoryDamageMelatoninAnimalsAnimals, newbornApoptosisCaspase 3CognitionDisease models, animalDrug evaluation, preclinicalHypoxia-ischemia, brainMaleMaze learningMotor activityNootropic agentsRats, sprague-dawleyUridineArticle0003956000000092-s2.0-850110366078187165928126402NeurosciencesPyramidal Tracts; Cervical Cord; ParesisCaspase 3UridineCasp3 protein, ratCaspase 3Nootropic agentUridineAdolescentAnimal experimentAnimal modelAnimal tissueApoptosisArticleBrainCell damageCognitionControlled studyEnzyme analysisFemaleHypoxic ischemic encephalopathyLearningMaleNeuroprotectionNewbornNonhumanPriority journalProtein expressionRatReference memoryReflexSensorimotor functionWorking memoryAnimalCognitionDisease modelDrug effectsHypoxia-ischemia, brainMaze testMetabolismMotor activityPhysiologyPreclinical studyPsychologySprague dawley rat