In This Issue pubs.acs.org/chemneuro
Cite This: ACS Chem. Neurosci. 2018, 9, 1516−1516
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PSYCHEDELICS FOR TREATING MOOD DISORDERS
model, the authors screened seven heterospirocyclic γ-lactams, isolated from the marine fungus Aspergillus f umigatus, for antiseizure activity. Two of the compounds, pseurotin A2 and azaspirofuran A, were identified as hits with druglike activity, and are current lead compounds for the development of nextgeneration epilepsy medication.
ACS Chem. Neurosci. 2018.9:1516-1516. Downloaded from pubs.acs.org by 5.188.217.106 on 08/08/18. For personal use only.
■ Depression and anxiety are widespread and often debilitating mood disorders. Despite being extraordinarily common, we still lack effective and rapid treatments. Current standard-ofcare medications usually take several weeks for effects to be felt, often requiring several different drug combinations. Additionally, 30% of patients are nonresponsive to currently available medications. Increasingly, researchers are looking toward psychedelic alternatives, such as ketamine and psilocybin, as leads for the next generation of neurotherapeutics. Now, Cameron and co-workers (DOI: 10.1021/acschemneuro.8b00134) explore N,N-dimethyltryptamine (DMT), the principal hallucinogenic component of the psychoactive ayahuasca plant, as another potential alternative treatment for mood disorders. The authors investigated the effects of DMT on rodent behaviors relevant to depression and anxiety. They found that hallucinogenic doses of DMT produced anxiogenic responses in rats initially after dosing, but longer term antianxiety and antidepressant effects were observed.
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Recent advances in RNA sequencing have enabled profiling of the dynamic transcriptome, affording new insights into how gene expression is regulated at the level of RNA. Transcriptomic profiling of neurons can give important insights underlying gene expression patterns that transpire in response to stimuli, such as learning and memory formation. The dynamic and unstable nature of RNA, coupled with the fragility of neuronal cell systems, makes metabolic RNA profiling in neurons a unique challenge. To profile stimulus-induced RNA expression in specific neuronal populations, Zajaczkowski and co-workers (DOI: 10.1021/acschemneuro.8b00197) developed chemical tools for labeling newly transcribed RNA. Using 5-ethynyl-uracil (5E-Uracil), a nucleotide analogue that is incorporated into nascent RNA, in combination with the enzyme uracil phophoribosyltransferase (UPRT), which drives this incorporation and can be overexpressed in discrete cell populations, the authors were able to label nascent RNA transcribed in primary cortical neurons in vitro. The ethynyl group on 5EUracil acts as a handle for bioconjugation of RNA to fluorophores or other enrichment methods, and the spatiotemporal control afforded by the UPRT system enables tracking of stimulus-responsive transcripts in specific neuronal populations.
SEARCHING THE SEA FOR NEW EPILEPSY DRUGS
Epilepsy, a neurological disorder characterized by spontaneous seizures, affects 70 million people worldwide. Approximately one-third of those affected are unresponsive to current antiseizure drugs. In the search for new drugs, many continue to explore natural products for new leads to treat epilepsy. In this issue, Copmans et al. (DOI: 10.1021/acschemneuro.8b00060) perform systematic large-scale screening of marine-derived natural products to discover potential new antiseizure drugs. Marine species provide a rich source of novel bioactive structures not observed on land. Using a zebrafish © 2018 American Chemical Society
RNA LABELING IN NEURONS
Published: July 18, 2018 1516
DOI: 10.1021/acschemneuro.8b00328 ACS Chem. Neurosci. 2018, 9, 1516−1516
