Neonatal propofol anesthesia modifies activity-dependent processes and induces transient hyperlocomotor response to d-amphetamine during adolescence in rats.
This study examined the influence of propofol anesthesia on the expression of activity-regulated molecules (BDNF and c-Fos) and synaptic plasticity markers (synaptophysin, GAP-43, drebrin) in the frontal cortex and thalamus of 7-day-old (P7) rats. Although these brain regions are the main targets of anesthetic action, they are contained in the cortico-striato-thalamo-cortical feedback loops, involved in naturally occurring and drug-induced psychoses. Therefore, functional integrity of these loops was examined in adolescent and adult rats through d-amphetamine-induced hyperactivity. Propofol treatment (25mg/kg) decreased exon-specific and total BDNF mRNA expression in the frontal cortex and thalamus, in a time-dependent manner. BDNF protein level was increased in the frontal cortex and decreased in the thalamus, which was accompanied by the change of phospho-TrkB expression. Similarly to BDNF, the expression of c-Fos was decreased in the frontal cortex while it was changed only at the protein level in the thalamus. Synaptic plasticity markers changed in a time- and region-specific manner, indicating increased synaptogenesis in the frontal cortex and synapse elimination in the thalamus in P7 rats after the propofol anesthesia exposure. These early molecular changes were followed by time-related, increased motor reaction to d-amphetamine in adolescent, but not in adult rats. Our study revealed that exposure of immature brain to propofol anesthesia during the critical phase of development provoked immediate changes in activity-dependent processes and synaptic adjustment, influencing brain capacity to integrate later developmental events and resulting in temporary altered response to acute psychotropic stimulation during adolescence.
Department of Neurobiology, Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia. Electronic address: vesnav@ibiss.bg.ac.rs.
Vesna
V
Pešić
Department of Neurobiology, Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
Desanka
D
Milanović
Department of Biochemistry and Goodman Cancer Research Centre, McGill University, 1160 Pine Ave. West, H3A 1A3, Montreal, QC, Canada.
Jelena
J
Popić
Department of Neurobiology, Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
Kosara
K
Smiljanić
Department of Neurobiology, Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
Vesna
V
Tešić
Department of Neurobiology, Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
Selma
S
Kanazir
Department of Anesthesiology, University of Virginia Health System, Charlottesville, VA, USA.
Vesna
V
Jevtović-Todorović
Department of Neurobiology, Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia. Electronic address: sabir@ibiss.bg.ac.rs.
Sabera
S
Ruždijić
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D003913:Dextroamphetamine / Q000633:toxicity*; D019922:GAP-43 Protein / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006948:Hyperkinesis / Q000139:chemically induced* / Q000188:drug therapy*; D006993:Hypnotics and Sedatives / Q000627:therapeutic use*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D015742:Propofol / Q000627:therapeutic use*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D000697:Central Nervous System Stimulants; D019922:GAP-43 Protein; D006993:Hypnotics and Sedatives; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; C053386:drebrins; D003913:Dextroamphetamine; D015742:Propofol
BDNF transcripts; Locomotor activity; Propofol anesthesia; Synaptophysin; Trk-B; c-Fos