Project description:Methamphetamine abuse continues to be a worldwide problem, damaging the individual user as well as society. Only minimal information exists on molecular changes in the brain that result from methamphetamine administered in patterns typical of human abusers. In order to investigate such changes, we examined the effect of methamphetamine on the transcriptional profile in brains of monkeys. Gene expression profiling of the caudate and hippocampus identified protein disulfide isomerase family member A3 (PDIA3) to be significantly up-regulated in the animals treated with methamphetamine as compared to saline treated control monkeys. Treatment of primary rat neurons with methamphetamine revealed an up-regulation of PDIA3, showing a direct effect of methamphetamine on neurons to increase PDIA3. In vitro studies using a neuroblastoma cell line demonstrated that PDIA3 expression protects against methamphetamine-induced cell toxicity and methamphetamine-induced intracellular reactive oxygen species production, revealing a neuroprotective role for PDIA3. The current study implicates PDIA3 to be an important cellular neuroprotective mechanism against a toxic drug, and as a potential target for therapeutic investigations. To study the effects of chronic METH effects on the brain
Project description:To explore how brains change upon species evolution, we generated the first whole central brain comparative single-cell transcriptomic atlases of three closely-related but ecologically-distinct drosophilids: D. melanogaster, D. simulans and D. sechellia. D. melanogaster and D. simulans are cosmopolitan generalists, while the island endemic D. sechellia exhibits extreme niche specialism on the ripe noni fruit of the Morinda citrifolia shrub. The global cellular composition of central brains is well-conserved in the three Drosophila species, but we predicted a few cell types (perineurial glia, sNPF and Dh44 neurons) with divergent frequencies. Gene expression analysis revealed that distinct cell types within the central brain evolve at different rates and patterns; notably, several glial cell types exhibit the greatest divergence between species. Compared to D. melanogaster, the cellular composition and gene expression patterns of the central brain in D. sechellia displays greater deviation than those of D. simulans, indicating that the distinctive ecological specialization of D. sechellia is reflected in the structure and function of its brain. Gene expression changes in D. sechellia encompass metabolic and ecdysone signaling genes, indicative of adaptations to its novel ecological demands. Additional single-cell transcriptomic analysis on D. sechellia revealed genes and cell types responsive to noni juice supplementation, showing glial cells as key sites for both physiological and genetic adaptation to novel conditions. Our comparative transcriptomic atlases of drosophilid brains will provide an entry point to more broadly study the evolvability of nervous systems across and beyond the Drosophila genus.
Project description:Diplonema papillatum represents a group of highly diverse and abundant marine protists with still unknown lifestyle and ecological functions. Based on alterations of the transcriptomic, proteomic and metabolomic profiles obtained from cells grown under different conditions we designed a metabolic map of its cellular bioenergetic pathways. Comparative analysis in the nutrient-rich and -poor media and in the absence and presence of oxygen revealed a capacity for major metabolic reprograming. D. papillatum is equipped with fundamental metabolic routes such as glycolysis, gluconeogenesis, TCA cycle, pentose phosphate pathway, respiratory complexes, β-oxidation and synthesis of fatty acid. While gluconeogenesis uniquely dominates over glycolysis, TCA cycle represents a combination of standard and unusual enzymes. The presence of typical anaerobic enzymes such as pyruvate:NADP+ oxidoreductase, fumarate reductase, opine dehydrogenase, enoyl-coenzyme A reductase, and lactate dehydrogenase reflects the ability to survive in low-oxygen environments. The metabolism quickly reacts to restricted carbon source, revealing unusual flexibility of diplonemids, also reflected in cell morphology and motility, which is in good correlation with their extreme ecological valence.