Ontology highlight
ABSTRACT:
PROVIDER: PRJNA783014 | ENA |
REPOSITORIES: ENA
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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:This study examined the functional response of a host (zebrafish) to implantation of a conspecific or allospecific (goldfish) gastrointestinal (GIT) microbiome followed by diet manipulation and the repercussions of these manipulations on host GIT physiology. Implantation of a native zebrafish biome successfully reintroduced wildtype (WT) communities with the exception of several rare, phylogenetically distant species. Implantation of a foreign goldfish biome created communities that were distinct from WT, suggesting that the seeding community created substantial differences from the native host communities. A mismatched ?natural? diet and an implanted allospecific biome enriched for rarer and more phylogenetically diverse bacteria. Transcriptional changes within the GIT clustered in relationship to biome treatments, mirroring clustering of biome implants. Implantation of an allospecific biome along with an altered diet markedly down-regulated approximately 70% of the transcripts involved in cholesterol biosynthesis, while tissue content analysis revealed an increase in total tissue cholesterol. Furthermore, transcripts involved in lipogenesis pathways were significantly downregulated and correlated with a striking decrease in intestinal lipase activity driven by both biome and diet. Glucose-6P dehydrogenase (G6PD) activities increased during dietary manipulations regardless of biome, while the allospecific biome down-regulated transcripts involved in gluconeogenesis and altered glucokinase (GK) and hexokinase (HK) activities regardless of diet. However, growth rates did not reveal an impact of these responses. Adult zebrafish are unable to reform proportional representation within bacterial communities following transplantation of an allospecific biome resulting in transcriptional and enzymatic alterations for lipid and carbohydrate metabolism that did not affect overall animal homeostasis.
2018-08-30 | GSE118496 | GEO
Project description:Intraperitoneal administration of ferric nitrilotriacetate initiates Fenton reaction in the renal proximal tubules in rodents. Its repeated administration ultimately leads to the development of renal cell carcinoma (RCC). We performed high-resolution microarray comparative genomic hybridization to identify characteristics in the genomic profiles of oxidative stress-induced RCCs in the mice of A/J strain.
2022-01-07 | GSE183173 | GEO
Project description:Mirounga angustirostris blubber transcriptome response to repeated ACTH administration
| PRJNA485363 | ENA
Project description:We have undertaken the first comprehensive analysis of gene expression influenced by acute LSD administration in the mammalian brain to elucidate the mechanism of action of this class of drugs. We have identified a number of genes that are predicted to be involved in the processes of synaptic plasticity, glutamatergic signaling and cytoskeletal architecture. Understanding these molecular events will lead to new insights into the etiology of disorders whose behavioral symptoms resemble the temporary effects of hallucinogenic drugs, and also may ultimately result in new therapies.
2021-11-11 | GSE179378 | 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:Immune system responses against adeno-associated virus (AAV) vectors are potentiated after the first administration, which has prevented the clinical use of repeated administration of AAV-based gene therapies. Here, we quantify the contributions of multiple immune system components towards AAV response in mice. We identify B-cell-mediated immunity, specifically the generation of IgM antibodies, as a critical component preventing vector re-administration.
2022-11-06 | GSE200223 | GEO
Project description:Here we show that Tet1 is down-regulated in mouse nucleus accumbens (NAc), a key brain reward structure, by repeated cocaine administration which enhances behavioral responses to cocaine. Through genome-wide 5hmC profiling, we identified 5hmC changes selectively clustered in both enhancer and coding regions of genes with several annotated neural functions. By coupling with mRNA sequencing, we found cocaine-induced alterations in 5hmC correlate positively with alternative splicing. We also demonstrated that 5hmC alteration at certain genes lasts up to a month after cocaine exposure. DNA Nac samples were collected at various time points after 7 daily cocaoine ip administration for 5hmC and transcriptome analysis
2015-02-23 | E-GEOD-63747 | biostudies-arrayexpress