title: Post-anesthesia AMPA receptor potentiation prevents anesthesia-induced learning and synaptic deficits.
abstract: Accumulating evidence has shown that repeated exposure to general anesthesia during critical stages of brain development results in long-lasting behavioral deficits later in life. To date, there has been no effective treatment to mitigate the neurotoxic effects of anesthesia on brain development. By performing calcium imaging in the mouse motor cortex, we show that ketamine anesthesia causes a marked and prolonged reduction in neuronal activity during the period of post-anesthesia recovery. Administration of the AMPAkine drug CX546 [1-(1,4-benzodioxan-6-ylcarbonyl)piperidine] to potentiate AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor activity during emergence from anesthesia in mice enhances neuronal activity and prevents long-term motor learning deficits induced by repeated neonatal anesthesia. In addition, we show that CX546 administration also ameliorates various synaptic deficits induced by anesthesia, including reductions in synaptic expression of NMDA (N-methyl-d-aspartate) and AMPA receptor subunits, motor training-evoked neuronal activity, and dendritic spine remodeling associated with motor learning. Together, our results indicate that pharmacologically enhancing neuronal activity during the post-anesthesia recovery period could effectively reduce the adverse effects of early-life anesthesia.
authors.affiliation: Department of Anesthesiology, Perioperative Care, and Pain Medicine, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Lianyan
authors.initials: L
authors.lastname: Huang
authors.affiliation: Medical Scientist Training Program at New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Cichon
authors.affiliation: Department of Psychiatry, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Ipe
authors.initials: I
authors.lastname: Ninan
authors.affiliation: Department of Anesthesiology, Perioperative Care, and Pain Medicine, New York University School of Medicine, New York, NY 10016, USA. guang.yang@med.nyu.edu.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
mesh_terms: D000758:Anesthesia / Q000009:adverse effects*; D000818:Animals; D015153:Blotting, Western; D004149:Dioxoles / Q000494:pharmacology; D007858:Learning / Q000187:drug effects; D051379:Mice; D016202:N-Methylaspartate / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D018091:Receptors, AMPA / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: C443080:1-(1,4-benzodioxan-6-ylcarbonyl)piperidine; D004149:Dioxoles; D010880:Piperidines; D018091:Receptors, AMPA; D016202:N-Methylaspartate