Similar Datasets
Project description:Chronic administration of lysergic acid diethylamide (LSD) every other day to rats results in a variety of abnormal behaviors. These build over the 90 day course of treatment and can persist at full strength for at least several months after cessation of treatment. The behaviors are consistent with those observed in animal models of schizophrenia and include hyperactivity, reduced sucrose-preference, and decreased social interaction. In order to elucidate molecular changes that underlie these aberrant behaviors, we chronically treated rats with LSD and performed RNA-sequencing on the medial prefrontal cortex (mPFC), an area highly associated with both the actions of LSD and the pathophysiology of schizophrenia and other psychiatric illnesses. Results: We observed widespread changes in the neurogenetic state of treated animals four weeks after cessation of LSD treatment. QPCR was used to validate a subset of gene expression changes observed with RNA-Seq, and confirmed a significant correlation between the two methods. Functional clustering analysis indicates differentially expressed genes are enriched in pathways involving neurotransmission (Drd2, Gabrb1), synaptic plasticity (Nr2a, Krox20), energy metabolism (Atp5d, Ndufa1) and neuropeptide signaling (Npy, Bdnf), among others. Many processes identified as altered by chronic LSD are also implicated in the pathogenesis of schizophrenia, and genes affected by LSD are enriched with putative schizophrenia genes. Our results provide a relatively comprehensive analysis of mPFC transcriptional regulation in response to chronic LSD, and indicate that the long-term effects of LSD may bear relevance to psychiatric illnesses, including schizophrenia.
2021-11-11 | GSE179379 | GEO
Project description:We treated the T-ALL cell line MOLT4 with a novel LSD inhibitor and performed ChIP-seq analysis using anti-histoneH3K27ac antibody to assess the enhancer function.
2018-09-22 | GSE120314 | GEO
Project description:Serotonin (5-hydroxytryptamine; 5-HT) 5-HT2-family receptors are the key targets of the prototypical psychedelic LSD. Although the canonical signaling pathway for 5-HT2 receptors is mediated by Gq protein, recent studies suggest that G-protein independent signaling, namely β-arrestin signaling pathway, may be also essential for actions of LSD in vitro and in vivo. To gain comprehensive molecular insights into the signaling mechanisms of LSD, we determined the cryoEM structures of LSD-bound 5-HT2BR in transducer-free state, G protein-coupled state and β-arrestin-1-coupled state, respectively. Besides, we use mass spectrometry to determine the phosphorylation sites of LSD-bound 5-HT2BR.
2023-10-24 | PXD030752 | Pride
Project description:Inherited metabolic diseases belong to the group of rare diseases (so called ‘orphan diseases’) whose incidence is less than 1: 5 000 live births. Among these diseases the lysosomal storage diseases (LSD) are also distinguished, which are caused by disorders in the lysosomal system resulting from the mutations in the genes coding for lysosomal hydrolases, cofactors, enzymes involved in the posttranslational processing, and proteins present in the lysosomal membrane. Although about 70 LSD are recognized so far, their pathomechanism is almost unknown. Hitherto existing results of scientific investigations indicate that different cellular pathways and events are involved in the pathogenic processes: autophagy, apoptosis, toxic action of lyso- derivatives of lipid compounds, disordered Ca2+ ions intracellular homeostasis, secondary storage of macromolecular compounds, signal transduction, inflammatory processes, deficient by-products and many more. We are especially interested in the explanation of pathomechanisms of Gaucher disease and Niemann-Pick type C disease (for the latter disease there is no therapy officially accepted). In this project we aim to experimentally explain: - which cellular pathways and mechanisms are activated and inactivated in cells originating from patients with different LSD and healthy individuals - are there differences in genes expression in different diseases - are gene expression changes related to known and observed biochemical and clinical changes.
2019-04-23 | GSE124283 | GEO
Project description:Lysergic acid diethylamide (LSD), considered the prototypical psychedelic molecule, has effects on consciousness and perception. However, the molecular mechanisms involved in LSD effects in human neural cells and how they may be translated into changes in physiology are still poorly understood. Here we used human cerebral organoids as a biological live model to explore the response of human brain cells to LSD. Mass spectrometry-based proteomics was performed to gain insights on molecular targets and signaling pathways involved in the mid and long-term effects of LSD.
2024-10-17 | PXD037814 | Pride
Project description:Lysergic acid diethylamide (LSD), considered the prototypical psychedelic molecule, has effects on consciousness and perception. However, the molecular mechanisms involved in LSD effects in human neural cells and how they may be translated into changes in physiology are still poorly understood. Here we used human cerebral organoids as a biological live model to explore the response of human brain cells to LSD. Mass spectrometry-based proteomics was performed to gain insights on molecular targets and signaling pathways involved in the mid and long-term effects of LSD.
2024-10-17 | PXD027369 | Pride
Project description:To investigate the role for LSD1 under hypoxia condition. we depleted LSD1 gene with siRNA in Huh-1 cell lines under 1% O2 hypoxia condtion, and than perforemed gene expression microarray analysis. Using Gene Set Enrichment Analysis (GSEA), determined to identify the biological pathway. Determined the gene expression profile of the LSD konckdown effect under hypoxia condition. Using Gene Set Enrichment Analysis (GSEA) decided to identify the biological pathways.
2016-08-10 | E-GEOD-85345 | biostudies-arrayexpress
Project description:The accumulation of α-synuclein (ASyn) has been observed in several lysosomal storage diseases (LSD), but it remains unclear if the accumulation of ASyn contributes to the pathology. The mitochondria degeneration, reduced expression of manganese superoxide dismutase 2, and reactive oxygen species-mediated oxidative damage were observed in the neurons of Hexb-/- mice. Gene expression in the brain of 14-week-old Hexb-/- ASyn+/+, Hexb-/- Asyn-Tg, and Hexb-/- ASyn-/- mice were analyzed.
2015-05-12 | E-GEOD-68748 | biostudies-arrayexpress
Project description:The accumulation of α-synuclein (ASyn) has been observed in several lysosomal storage diseases (LSD), but it remains unclear if the accumulation of ASyn contributes to the pathology. The mitochondria degeneration, reduced expression of manganese superoxide dismutase 2, and reactive oxygen species-mediated oxidative damage were observed in the neurons of Hexb-/- mice.
2015-05-12 | GSE68748 | GEO