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
Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. Although prescribed for dyslipidemia and type-II diabetes, PPAR agonists also possess anti-addictive characteristics. PPAR agonists decrease ethanol consumption and reduce withdrawal severity and susceptibility to stress-induced relapse in rodents. However, the cellular and molecular mechanisms facilitating these properties have yet to be investigated. We tested three PPAR agonists in a continuous access two-bottle choice (2BC) drinking paradigm and found that tesaglitazar (PPARα/γ; 1.5 mg/kg) and fenofibrate (PPARα; 150 mg/kg) decreased ethanol consumption in male C57BL/6J mice while bezafibrate (PPARα/γ/β; 75 mg/kg) did not. We hypothesized that changes in brain gene expression following fenofibrate and tesaglitazar treatment lead to reduced ethanol drinking. We studied unbiased genomic profiles in areas of the brain known to be important for ethanol dependence, the prefrontal cortex (PFC) and amygdala, and also profiled gene expression in liver. Genomic profiles from the non-effective bezafibrate treatment were used to filter out genes not associated with ethanol consumption. Because PPAR agonists are anti-inflammatory, they would be expected to target microglia and astrocytes. Surprisingly, PPAR agonists produced a strong neuronal signature in mouse brain, and fenofibrate and tesaglitazar (but not bezafibrate) targeted a subset of GABAergic interneurons in the amygdala. Weighted gene co-expression network analysis (WGCNA) revealed co-expression of treatment-significant genes. Functional annotation of these gene networks suggested that PPAR agonists might act via neuropeptide and dopaminergic signaling pathways in the amygdala. Our results reveal gene targets through which PPAR agonists can affect alcohol consumption behavior.
Authors:
Laura B Ferguson, Dana Most, Yuri A Blednov, R Adron Harris
Average rotarod training latency Chr# 5 rs13478110 (9741228) with right flanking marker rs13478092(3595407) and left marker rs3718776 (150393227). This was mapped in 300 + (b6x129)F2 mice.
QTL associated with p-glycoprotein positive CD4 T cell subset 2. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (45152335)
QTL associated with vertebral trabecular bone trait 15. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (45159272)
Authors:
Bouxsein ML, Uchiyama T, Rosen CJ, Shultz KL, Donahue LR, Turner CH, Sen S, Churchill GA, Mller R, Beamer WG
Kyoto Encyclopedia of Genes and Genomes (KEGG) Geneset. This geneset contains genes that participate in the "Alcoholism" pathway. This set was automatically constructed using the KEGG API and enumerating all mouse pathways.
gene2kegg v. 0.1.1
Last updated 2015.09.10
QTL for nicotine sensitivity on Chr13 at D13Mit59 (37.58 Mbp , Build 37)
Description:
nicotine sensitivity spans 12.58 - 62.58 Mbp (NCBI Build 37) on Chr13. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
QTL for ethanol withdrawal on Chr13 at D13Ncvs35 (71.29 Mbp , Build 37)
Description:
ethanol withdrawal spans 46.29 - 96.29 Mbp (NCBI Build 37) on Chr13. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
QTL associated with spontaneous crescentic glomerulonephritis QTL 5. The confidence interval is Chr13:35968794-96872609 bp,+strand
Authors:
Hamano Y, Tsukamoto K, Abe M, Sun GD, Zhang D, Fujii H, Matsuoka S, Tanaka M, Ishida-Okawara A, Tachikawa H, Nishimura H, Tokunaka K, Hirose S, Suzuki K
QTL associated with Angiostrongylus costaricensis nematode susceptibility 2. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (53042863)
QTL associated with castaneus 10 week body weight 4. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (72374309)
QTL associated with cystic fibrosis body weight 5. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (55673906)
QTL associated with cocaine induced activation 11. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (54579545)
QTL associated with "cerebellum pattern fissures, declival 5". This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (56582797)
QTL associated with circadian period of locomotor activity 11. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (55673906)
Authors:
Hofstetter JR, Trofatter JA, Kernek KL, Nurnberger JI, Mayeda AR
QTL associated with Crh transcript abundance QTL 3. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (56786703)
QTL associated with experimental allergic encephalomyelitis susceptibility 13. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (67271283)
Authors:
Butterfield RJ, Blankenhorn EP, Roper RJ, Zachary JF, Doerge RW, Sudweeks J, Rose J, Teuscher C
GeneWeaver