PMID- 29559371 OWN - NLM STAT- MEDLINE DCOM- 20190415 LR - 20211204 IS - 1878-4216 (Electronic) IS - 0278-5846 (Linking) VI - 86 DP - 2018 Aug 30 TI - Intravenous infusion of xenon-containing liposomes generates rapid antidepressant-like effects. PG - 140-149 LID - S0278-5846(17)31040-0 [pii] LID - 10.1016/j.pnpbp.2018.03.011 [doi] AB - AIM: Similar to ketamine, xenon gas acts as a glutamatergic N-methyl-(d)-aspartate receptor antagonist, but devoid of propensity to cause untoward effects. Herein, we loaded xenon gas into a liposomal carrier called xenon-containing liposomes (Xe-liposome) for systemic delivery, and investigated its effect as an antidepressant and also analyzed synaptic biomarkers including brain-derived neurotrophic factor (BDNF), protein kinase B (AKT), mammalian target of rapamycin (mTOR), protein kinase C (PKC) and extracellular signal-regulated kinase-1/2 (ERK1/2) in blood and brain. METHODS: Xe-liposomes (15 mul/mg) were prepared by a pressurized freeze-thaw method, and injected via the lateral tail vein (0.6 mL/rat) in male Wistar rats. The uncaging of xenon gas from circulating Xe-liposome was facilitated by continuous ultrasound application externally on the neck over the internal common carotid artery. One-hour after Xe-liposome infusion, animals were assessed for depression-like behaviors using a forced swimming test (FST), and spontaneous locomotor activity. Blood, as well as frontal cortex and hippocampal samples were obtained for immunoblotting and/or enzyme-linked immune sorbent assays. RESULTS: Acute intravenous infusion of Xe-liposome, at 6 mg/kg, showed an increase in swimming time in the FST (p < 0.006), indicating antidepressant-like phenotypes. Higher doses of Xe-liposomes (9 mg/kg) failed to improve swimming duration. This behavioral discrepancy was not associated with locomotion aberrations, as gross activity of rats remained similar for both doses. In biochemical analyses of frontal cortex, protein levels of BDNF increased by 64%, and enhanced phosphorylation of AKT (43%) and mTOR (93%) was observed at the 6 mg/kg dose level of Xe-liposomes, while these biomarkers and phosphorylated PKC and ERK1/2 levels remained unchanged at the higher dose. Moreover, Xe-liposomal treatment did not change the plasma and protein levels of BDNF, and phosphorylated AKT, mTOR, PKC and ERK1/2 hippocampal expressions. CONCLUSION: Xe-liposomes mediate a rapid antidepressant-like effect through activation of AKT/mTOR/BDNF signaling pathway. CI - Published by Elsevier Inc. FAU - Dandekar, Manoj P AU - Dandekar MP AD - Department of Internal Medicine, Division of Cardiology, The University of Texas Health Science Center at Houston (UTHealth), McGovern Medical School, Houston, TX, USA. FAU - Peng, Tao AU - Peng T AD - Department of Internal Medicine, Division of Cardiology, The University of Texas Health Science Center at Houston (UTHealth), McGovern Medical School, Houston, TX, USA; Center for Clinical and Translational Sciences, The University of Texas Health Science Center at Houston, USA. FAU - McPherson, David D AU - McPherson DD AD - Department of Internal Medicine, Division of Cardiology, The University of Texas Health Science Center at Houston (UTHealth), McGovern Medical School, Houston, TX, USA; Center for Clinical and Translational Sciences, The University of Texas Health Science Center at Houston, USA; Department of Biomedical Sciences, The University of Texas Medical School at Houston, USA; Memorial Hermann Heart and Vascular Institute-Texas Medical Center, USA. FAU - Quevedo, Joao AU - Quevedo J AD - Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA; Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA; Neuroscience Graduate Program, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA.; Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciuma, SC, Brazil. FAU - Soares, Jair C AU - Soares JC AD - Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston (UTHealth), McGovern Medical School, Houston, TX, USA. FAU - Huang, Shao-Ling AU - Huang SL AD - Department of Internal Medicine, Division of Cardiology, The University of Texas Health Science Center at Houston (UTHealth), McGovern Medical School, Houston, TX, USA; Center for Clinical and Translational Sciences, The University of Texas Health Science Center at Houston, USA. Electronic address: shaoling.huang@uth.tmc.edu. LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20180317 PL - England TA - Prog Neuropsychopharmacol Biol Psychiatry JT - Progress in neuro-psychopharmacology & biological psychiatry JID - 8211617 RN - 0 (Antidepressive Agents) RN - 0 (Bdnf protein, rat) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Depsipeptides) RN - 0 (Liposomes) RN - 0 (MA026 compound) RN - 3H3U766W84 (Xenon) RN - EC 2.7.1.1 (mTOR protein, rat) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - Antidepressive Agents/*administration & dosage MH - Brain-Derived Neurotrophic Factor/blood MH - Depressive Disorder/*drug therapy/metabolism MH - Depsipeptides MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Infusions, Intravenous MH - Liposomes MH - Motor Activity/drug effects MH - Proto-Oncogene Proteins c-akt/metabolism MH - Random Allocation MH - Rats, Wistar MH - TOR Serine-Threonine Kinases/metabolism MH - Xenon/*administration & dosage OTO - NOTNLM OT - AKT OT - BDNF OT - Depression OT - Forced swimming test OT - Xenon OT - mTOR EDAT- 2018/03/22 06:00 MHDA- 2019/04/16 06:00 CRDT- 2018/03/22 06:00 PHST- 2017/12/21 00:00 [received] PHST- 2018/02/26 00:00 [revised] PHST- 2018/03/09 00:00 [accepted] PHST- 2018/03/22 06:00 [pubmed] PHST- 2019/04/16 06:00 [medline] PHST- 2018/03/22 06:00 [entrez] AID - S0278-5846(17)31040-0 [pii] AID - 10.1016/j.pnpbp.2018.03.011 [doi] PST - ppublish SO - Prog Neuropsychopharmacol Biol Psychiatry. 2018 Aug 30;86:140-149. doi: 10.1016/j.pnpbp.2018.03.011. Epub 2018 Mar 17.