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

Su Chung Youn, Li You Chen, Ruei Jen Chiou, Te Jen Lai, Wen Chieh Liao, Fu Der Mai, Hung Ming Chang

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7 Citations (Scopus)

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.

Original languageEnglish
Article number18420
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - Dec 17 2015

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Secondary Ion Mass Spectrometry
Oxidative Stress
Pharmaceutical Preparations
Neuronal Plasticity
Deoxyglucose
Electron Transport Complex IV
Lipid Peroxidation
Hippocampus
Immunohistochemistry
Cognitive Dysfunction
Water

ASJC Scopus subject areas

  • General

Cite this

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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.",
author = "Youn, {Su Chung} and Chen, {Li You} and Chiou, {Ruei Jen} and Lai, {Te Jen} and Liao, {Wen Chieh} and Mai, {Fu Der} and Chang, {Hung Ming}",
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AU - Chiou, Ruei Jen

AU - Lai, Te Jen

AU - Liao, Wen Chieh

AU - Mai, Fu Der

AU - Chang, Hung Ming

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