Theophylline causes dose dependent persistent behavioural changes in neonatal mice
(English)Manuscript (preprint) (Other academic)
Theophylline is used in clinic to promote breathing in premature infants and in neonates. Caffeine, a compound also belonging to the group of xanthenes, is known to increase apoptosis and to cause behavioural defects. The present study was conducted to investigate whether theophylline can induce neuronal death and behavioural disturbances when administered to neonatal mice during a period of brain growth corresponding to premature infants and an approximately week 13 to 24.
Neonatal mice, three days old, were exposed to theophylline at doses 1, 5, or 25 mg/kg body weight twice daily for five consecutive days. Controls received in the same manner the vehicle, saline. Neuronal death was assessed in whole brain sections by Fluoro Jade 24 hours after the last exposure to theophylline. Adult mice, age 55 to 63 days old, were observed for spontaneous behavior in a novel home environment, learning and memory in a radial arm maze and for anxiety-like behavior in an elevated plus maze.
Adult mice neonatally exposed to theophylline showed significant dose-response changes in all three behavioural tests. The lowest dose to induce any behavioral defects was 5 mg/kg body weight. No significant alterations in neuronal death were observed in the neonatal brains.
The present study shows that neonatal exposure to theophylline can cause behavioural defects related to learning and memory impairments and reduced cognitive function in young adult mice.
neonatal, apoptosis, theophylline, behaviour, mice, learning
Anesthesiology and Intensive Care
Research subject Medicine
IdentifiersURN: urn:nbn:se:uu:diva-173786OAI: oai:DiVA.org:uu-173786DiVA: diva2:525182