The current study used two inbred mouse strains, C57BL/6 J and A/J, to investigate the genetics of behavioral responses to fentanyl. Mice were tested for conditioned place preference and fentanyl-induced locomotor activity. C57BL/6J mice formed a conditioned place preference to fentanyl injections and fentanyl increased their activity. Neither effect was noted in A/J mice. We conducted RNA-sequencing on the nucleus accumbens of mice used for fentanyl-induced locomotor activity. Surprisingly, we noted few differentially expressed genes using treatment as the main factor. However many genes differed between strains.
Authors:
Samuel J Harp, Mariangela Martini, Will Rosenow, Larry D Mesner, Hugh Johnson, Charles R Farber, Emilie F Rissman
Differential gene expression in nucleus accumbens somatostatin interneurons_cocaine_mice_pvalue
Description:
To characterize transcriptional alterations that cocaine induces in these cells, we perform cell type-specific RNA-sequencing on FACS-isolated nuclei of somatostatin interneurons and identified 1100 DETs enriched for processes related to neural plasticity. To profile the entire (non poly-A selected) transcriptome of NAc somatostatin interneurons, we generated a transgenic reporter line (SST-TLG498 mice) to label the nuclei of these cells with a modified form of EGFP that is retained in the nuclear membrane (EGFP-F)22, enabling their isolation from NAc dissections using FACS. We succeeded in FACS-isolating nuclei suitable for RNA-sequencing from individual SST-TLG498 mice. We proceeded with differential expression analysis of the RNA-sequencing data to identify differentially expressed transcripts (DETs) in NAc somatostatin interneurons in response to repeated cocaine exposure: 778 transcripts were upregulated by cocaine and 322 were downregulated.
Authors:
Efrain A Ribeiro, Marine Salery, Joseph R Scarpa, Erin S Calipari, Peter J Hamilton, Stacy M Ku, Hope Kronman, Immanuel Purushothaman, Barbara Juarez, Mitra Heshmati, Marie Doyle, Casey Lardner, Dominicka Burek, Ana Strat, Stephen Pirpinias, Ezekiell Mouzon, Ming-Hu Han, Rachael L Neve, Rosemary C Bagot, Andrew Kasarskis, Ja Wook Koo, Eric J Nestler
Alcohol transcriptome changes in mice microglia total homogenate p-value
Description:
Microglia are fundamentally important immune cells within the central nervous system (CNS) that respond to environmental challenges to maintain normal physiological processes. Alterations in steady-state cellular function and over-activation of microglia can facilitate the initiation and progression of neuropathological conditions such as Alzheimer’s disease, Multiple Sclerosis, and Major Depressive Disorder. Alcohol consumption disrupts signaling pathways including both innate and adaptive immune responses that are necessary for CNS homeostasis. Coordinate expression of these genes is not ascertained from an admixture of CNS cell-types, underscoring the importance of examining isolated cellular populations to reveal systematic gene expression changes arising from mature microglia. Unbiased RNA-Seq profiling was used to identify gene expression changes in isolated prefrontal cortical microglia in response to recurring bouts of voluntary alcohol drinking behavior. The voluntary ethanol paradigm utilizes long-term consumption ethanol that results in escalated alcohol intake and altered cortical plasticity that is seen in humans. Gene coexpression analysis identified a coordinately regulated group of genes, unique to microglia, that collectively are associated with alcohol consumption. Genes within this group are involved in toll-like receptor signaling and transforming growth factor beta signaling. Network connectivity of this group identified Siglech as a putative hub gene and highlighted the potential importance of proteases in the microglial response to chronic ethanol. In conclusion, we identified a distinctive microglial gene expression signature for neuroimmune responses related to alcohol consumption that provides valuable insight into microglia-specific changes underlying the development of substance abuse, and possibly other CNS disorders.
Authors:
Gizelle M McCarthy, Sean P Farris, Yuri A Blednov, R Adron Harris, R Dayne Mayfield
"Interacting selectively and non-covalently with a ribonucleoside, a compound consisting of a purine or pyrimidine nitrogenous base linked to ribose." [GOC:mah]
"A metabolic process - chemical reactions and pathways, including anabolism and catabolism, by which living organisms transform chemical substances - which involves a single organism." [GOC:jl]
"Interacting selectively and non-covalently with a purine nucleoside, a compound consisting of a purine base linked either to ribose or deoxyribose." [GOC:hjd]
"Interacting selectively and non-covalently with a nucleoside, a compound consisting of a purine or pyrimidine nitrogenous base linked either to ribose or deoxyribose." [GOC:hjd]
Genes with particular expression in the Anterior olfactory nucleus, dorsal part. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Cortical amygdalar area, anterior part, layer 1. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Orbital area, lateral part, layer 1. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Cortical amygdalar area, anterior part. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Orbital area, ventrolateral part, layer 1. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Taenia tecta, dorsal part, layer 1. Data represent fold expression difference in structure versus grey matter average expression.
Differentially expressed genes in male Sprague-Dawley rats (300-375 g or 250-300 g) following cocaine administration. Gene expression was evaluated via RNA-seq. Data taken from Supplemental Table S1 (associated with Fig 2. E-F and H). Values presented are p-values. Data available at GEO with accession number GSE124055.
Authors:
Ashley E Lepack, Craig T Werner, Andrew F Stewart, Sasha L Fulton, Ping Zhong, Lorna A Farrelly, Alexander C W Smith, Aarthi Ramakrishnan, Yang Lyu, Ryan M Bastle, Jennifer A Martin, Swarup Mitra, Richard M O'Connor, Zi-Jun Wang, Henrik Molina, Gustavo Turecki, Li Shen, Zhen Yan, Erin S Calipari, David M Dietz, Paul J Kenny, Ian Maze
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