title: Comprehensive Application of Time-of-flight Secondary Ion Mass Spectrometry (TOF-SIMS) for Ionic Imaging and Bio-energetic Analysis of Club Drug-induced Cognitive Deficiency.
abstract: Excessive exposure to club drug (GHB) would cause cognitive dysfunction in which impaired hippocampal Ca(2+)-mediated neuroplasticity may correlate with this deficiency. However, the potential changes of in vivo Ca(2+) together with molecular machinery engaged in GHB-induced cognitive dysfunction has never been reported. This study aims to determine these changes in bio-energetic level through ionic imaging, spectrometric, biochemical, morphological, as well as behavioral approaches. Adolescent rats subjected to GHB were processed for TOF-SIMS, immunohistochemistry, biochemical assay, together with Morris water maze to detect the ionic, molecular, neurochemical, and behavioral changes of GHB-induced cognitive dysfunction, respectively. Extent of oxidative stress and bio-energetics were assessed by levels of lipid peroxidation, Na(+)/K(+) ATPase, cytochrome oxidase, and [(14)C]-2-deoxyglucose activity. Results indicated that in GHB intoxicated rats, decreased Ca(2+) imaging and reduced NMDAR1, nNOS, and p-CREB reactivities were detected in hippocampus. Depressed Ca(2+)-mediated signaling corresponded well with intense oxidative stress, diminished Na(+)/K(+) ATPase, reduced COX, and decreased 2-DG activity, which all contributes to the development of cognitive deficiency. As impaired Ca(2+)-mediated signaling and oxidative stress significantly contribute to GHB-induced cognitive dysfunction, delivering agent(s) that improves hippocampal bio-energetics may thus serve as a promising strategy to counteract the club drug-induced cognitive dysfunction emerging in our society nowadays.
authors.affiliation: Institute of Medicine, College of Medicine, Chung Shan Medical University, Taichung 40201.|Department of Anatomy, Faculty of Medicine, Chung Shan Medical University, Taichung 40201.
authors.forename: Su-Chung
authors.initials: SC
authors.lastname: Youn
authors.affiliation: Department of Anatomy, Faculty of Medicine, Chung Shan Medical University, Taichung 40201.
authors.forename: Li-You
authors.initials: LY
authors.lastname: Chen
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031.
authors.forename: Ruei-Jen
authors.initials: RJ
authors.lastname: Chiou
authors.affiliation: Institute of Medicine, College of Medicine, Chung Shan Medical University, Taichung 40201.
authors.forename: Te-Jen
authors.initials: TJ
authors.lastname: Lai
authors.affiliation: Department of Anatomy, Faculty of Medicine, Chung Shan Medical University, Taichung 40201.
authors.forename: Wen-Chieh
authors.initials: WC
authors.lastname: Liao
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Fu-Der
authors.initials: FD
authors.lastname: Mai
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031.
authors.forename: Hung-Ming
authors.initials: HM
authors.lastname: Chang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003952:Diagnostic Imaging / Q000379:methods*; D003576:Electron Transport Complex IV / Q000378:metabolism; D004734:Energy Metabolism; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D013287:Illicit Drugs; D015151:Immunoblotting; D007150:Immunohistochemistry; D007477:Ions / Q000032:analysis*; D015227:Lipid Peroxidation; D008297:Male; D018782:Maze Learning / Q000502:physiology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D018629:Spectrometry, Mass, Secondary Ion / Q000379:methods*
chemical_list: D002118:Calcium; D017362:Cyclic AMP Response Element-Binding Protein; D003576:Electron Transport Complex IV; D013287:Illicit Drugs; D007477:Ions; D052248:Nitric Oxide Synthase Type I; D016194:Receptors, N-Methyl-D-Aspartate; D000254:Sodium-Potassium-Exchanging ATPase