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

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.