PMID- 28840469 OWN - NLM STAT- MEDLINE DCOM- 20190508 LR - 20190508 IS - 1559-1182 (Electronic) IS - 0893-7648 (Print) IS - 0893-7648 (Linking) VI - 55 IP - 1 DP - 2018 Jan TI - Early Exposure to Ketamine Impairs Axonal Pruning in Developing Mouse Hippocampus. PG - 164-172 LID - 10.1007/s12035-017-0730-0 [doi] AB - Mounting evidence suggests that prolonged exposure to general anesthesia (GA) during brain synaptogenesis damages the immature neurons and results in long-term neurocognitive impairments. Importantly, synaptogenesis relies on timely axon pruning to select axons that participate in active neural circuit formation. This process is in part dependent on proper homeostasis of neurotrophic factors, in particular brain-derived neurotrophic factor (BDNF). We set out to examine how GA may modulate axon maintenance and pruning and focused on the role of BDNF. We exposed post-natal day (PND)7 mice to ketamine using a well-established dosing regimen known to induce significant developmental neurotoxicity. We performed morphometric analyses of the infrapyramidal bundle (IPB) since IPB is known to undergo intense developmental modeling and as such is commonly used as a well-established model of in vivo pruning in rodents. When IPB remodeling was followed from PND10 until PND65, we noted a delay in axonal pruning in ketamine-treated animals when compared to controls; this impairment coincided with ketamine-induced downregulation in BDNF protein expression and maturation suggesting two conclusions: a surge in BDNF protein expression "signals" intense IPB pruning in control animals and ketamine-induced downregulation of BDNF synthesis and maturation could contribute to impaired IPB pruning. We conclude that the combined effects on BDNF homeostasis and impaired axon pruning may in part explain ketamine-induced impairment of neuronal circuitry formation. FAU - Obradovic, Aleksandar Lj AU - Obradovic AL AD - Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA. FAU - Atluri, Navya AU - Atluri N AD - Department of Anesthesiology, University of Colorado School of Medicine, 12401 East 17th Avenue, Aurora, CO, 80045, USA. FAU - Dalla Massara, Lorenza AU - Dalla Massara L AD - Department of Anesthesiology and Pharmacology, University of Padua, Padua, Italy. FAU - Oklopcic, Azra AU - Oklopcic A AD - Department of Medicine, University of Virginia Health System, Charlottesville, VA, USA. FAU - Todorovic, Nikola S AU - Todorovic NS AD - University of Virginia College of Arts and Sciences, Charlottesville, VA, USA. FAU - Katta, Gaurav AU - Katta G AD - Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA. FAU - Osuru, Hari P AU - Osuru HP AD - Department of Anesthesiology, University of Colorado School of Medicine, 12401 East 17th Avenue, Aurora, CO, 80045, USA. FAU - Jevtovic-Todorovic, Vesna AU - Jevtovic-Todorovic V AD - Department of Anesthesiology, University of Colorado School of Medicine, 12401 East 17th Avenue, Aurora, CO, 80045, USA. vesna.jevtovic-todorovic@ucdenver.edu. LA - eng GR - R01 GM118197/GM/NIGMS NIH HHS/United States GR - R01 HD044517/HD/NICHD NIH HHS/United States GR - R21 HD080281/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 RN - 0 (Anesthetics, Dissociative) RN - 690G0D6V8H (Ketamine) SB - IM MH - Anesthetics, Dissociative/*toxicity MH - Animals MH - Animals, Newborn MH - Axons/*drug effects/*pathology MH - Hippocampus/*drug effects/growth & development/*pathology MH - Ketamine/*toxicity MH - Mice PMC - PMC5808855 MID - NIHMS901936 OTO - NOTNLM OT - Brain-derived neurotrophic factor OT - General anesthesia OT - Immature brain OT - Infrapyramidal bundle OT - Mossy fibers OT - Synaptogenesis EDAT- 2017/08/26 06:00 MHDA- 2019/05/09 06:00 PMCR- 2019/01/01 CRDT- 2017/08/26 06:00 PHST- 2017/08/26 06:00 [pubmed] PHST- 2019/05/09 06:00 [medline] PHST- 2017/08/26 06:00 [entrez] PHST- 2019/01/01 00:00 [pmc-release] AID - 10.1007/s12035-017-0730-0 [pii] AID - 10.1007/s12035-017-0730-0 [doi] PST - ppublish SO - Mol Neurobiol. 2018 Jan;55(1):164-172. doi: 10.1007/s12035-017-0730-0.