Gene expression analysis indicates CB1 receptor upregulation in the hippocampus and neurotoxic effects in the frontal cortex 3 weeks after single-dose MDMA administration in Dark Agouti rats.

BACKGROUND: 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is a widely used recreational drug known to impair cognitive functions on the long-run. Both hippocampal and frontal cortical regions have well established roles in behavior, memory formation and other cognitive tasks and damage of these regions is associated with altered behavior and cognitive functions, impairments frequently described in heavy MDMA users. The aim of this study was to examine the hippocampus, frontal cortex and dorsal raphe of Dark Agouti rats with gene expression arrays (Illumina RatRef bead arrays) looking for possible mechanisms and new candidates contributing to the effects of a single dose of MDMA (15 mg/kg) 3 weeks earlier. RESULTS: The number of differentially expressed genes in the hippocampus, frontal cortex and the dorsal raphe were 481, 155, and 15, respectively. Gene set enrichment analysis of the microarray data revealed reduced expression of 'memory' and 'cognition', 'dendrite development' and 'regulation of synaptic plasticity' gene sets in the hippocampus, parallel to the upregulation of the CB1 cannabinoid- and Epha4, Epha5, Epha6 ephrin receptors. Downregulated gene sets in the frontal cortex were related to protein synthesis, chromatin organization, transmembrane transport processes, while 'dendrite development', 'regulation of synaptic plasticity' and 'positive regulation of synapse assembly' gene sets were upregulated. Changes in the dorsal raphe region were mild and in most cases not significant. CONCLUSION: The present data raise the possibility of new synapse formation/synaptic reorganization in the frontal cortex three weeks after a single neurotoxic dose of MDMA. In contrast, a prolonged depression of new neurite formation in the hippocampus is suggested by the data, which underlines the particular vulnerability of this brain region after the drug treatment. Finally, our results also suggest the substantial contribution of CB1 receptor and endocannabinoid mediated pathways in the hippocampal impairments. Taken together the present study provides evidence for the participation of new molecular candidates in the long-term effects of MDMA

Role of hypogenesis in the evolution of karst in the Taurus Mountains Range, Turkey

Field observations and laboratory data collected from the Taurus Mountains Range, Turkey during the last two decades provided evidence for the link between the evolution of hypogene karst and the geodynamic history. Major evidence includes; carbonate-hosted secondary ore deposits that are converted from primarily hypogene minerals by epigene, oxygen-rich groundwater circulating at local to intermediate depths. Another piece of evidence of hypogene karst in the Tauride is the Kırkgöz springs’ huge submerged cave/conduit system, which formed the Antalya Travertine Plateau, which is the world’s largest deposit precipitated by cool karst groundwater. The obruks in central Tauride are giant collapse dolines formed by ascending hypogene fluids in the upper continental crust, rich in volcanogenic carbondioxide. The groundwater’s noble gas and carbon isotope data are helpful in determining the existing but asymptomatic hypogene activity in the upper crust. Hypogene karst development seems common in parts of the world with current or past geodynamic activity. However, a hydrogeological overview of the geodynamic history is essential to assess the hypogene processes and their reflections on the land surface