title: Neonatal exposure to propofol affects BDNF but not CaMKII, GAP-43, synaptophysin and tau in the neonatal brain and causes an altered behavioural response to diazepam in the adult mouse brain.
abstract: Animal studies have shown that neonatal anaesthesia is associated with acute signs of neurodegeneration and later behavioural changes in adult animals. The anaesthetic effect of propofol is thought to be mediated by γ-amino butyric acid (GABA)(A) receptors. The present study investigated the effects on proteins important for normal neonatal brain development (i.e. BDNF, CaMKII, GAP-43, synaptophysin and tau), and adult spontaneous motor and anxiety-like behaviours in response to diazepam, after neonatal exposure to propofol. Ten-day-old mice were exposed to 0, 10 or 60 mg/kg bodyweight propofol. Neonatal propofol exposure changed the levels of BDNF in the brain, 24h after exposure, but did not alter any of the other proteins. Neonatal propofol exposure significantly changed the adult response to the GABA-mimetic drug diazepam, manifest as no change in spontaneous motor activity and/or reduced sedative effect and an extinguished effect on the reduction of anxiety-like behaviours in an elevated plus maze. Although no adult spontaneous behavioural changes were detected after neonatal propofol exposure, the exposure caused an adult dose-dependent decrease in the response to the GABA-mimetic drug diazepam. These changes may be due to neonatal alterations in BDNF levels.
authors.affiliation: Department of Surgical Sciences, Anaesthesiology and Intensive Care, Uppsala University, Sweden. Emma.Ponten@surgsci.uu.se
authors.forename: Emma
authors.initials: E
authors.lastname: Pontén
authors.forename: Anders
authors.initials: A
authors.lastname: Fredriksson
authors.forename: Torsten
authors.initials: T
authors.lastname: Gordh
authors.forename: Per
authors.initials: P
authors.lastname: Eriksson
authors.forename: Henrik
authors.initials: H
authors.lastname: Viberg
mesh_terms: D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000009:adverse effects; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology*; D005260:Female; D018757:GABA Modulators / Q000494:pharmacology; D019922:GAP-43 Protein / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D015742:Propofol / Q000008:administration & dosage / Q000009:adverse effects*; D016708:Synaptophysin / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D018686:Anesthetics, Intravenous; D019208:Brain-Derived Neurotrophic Factor; D018757:GABA Modulators; D019922:GAP-43 Protein; D016708:Synaptophysin; D016875:tau Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D003975:Diazepam; D015742:Propofol