Project description:To characterize both short- and long-term (7 days and 28 days) gene expression profiling differences between control and MPTP-treated retina, we determined levels of gene expression using microarray analysis and real-time PCR. We found 60 genes relatively regulated in retinas treated with MPTP for 7 days (26 up-regulated and 34 down-regulated), whereas 54 genes were regulated in retinas treated with MPTP for 28 days (18 up-regulated and 36 down-regulated) when compared with the non-treated retina in each control groups. Total 26 annotated differently expressed genes were chosen for further validation by quantitative real-time PCR, and 4 genes in the 7-day treatment group (Clec2e; Dio2; Hmcn1; Rlbp1) and 3 genes in the 28-days treatment group (Pnmt; Tmem121; Ssxb3) were confirmed.
Project description:To characterize both short- and long-term (7 days and 28 days) gene expression profiling differences between control and MPTP-treated retina, we determined levels of gene expression using microarray analysis and real-time PCR. We found 60 genes relatively regulated in retinas treated with MPTP for 7 days (26 up-regulated and 34 down-regulated), whereas 54 genes were regulated in retinas treated with MPTP for 28 days (18 up-regulated and 36 down-regulated) when compared with the non-treated retina in each control groups. Total 26 annotated differently expressed genes were chosen for further validation by quantitative real-time PCR, and 4 genes in the 7-day treatment group (Clec2e; Dio2; Hmcn1; Rlbp1) and 3 genes in the 28-days treatment group (Pnmt; Tmem121; Ssxb3) were confirmed. Male C57BL/6 mice were randomly divided into four treatment groups (n= 6 in each group): the 7 days and 28 days saline-injection (control) groups (C-7 and C-28, respectively), and 7 days and 28 days MPTP-injection groups (M-7 and M-28, respectively). 4 retinas for 1 samples (1 gene chip), (4 experimental group × 2 samples of each experimental group = total 8 samples).
Project description:Long term exposure to incretin hormones is known to have salutory effects on beta cell function and viability. While short-term cAMP induction is known to have a signature CREB-CRTC target gene response, the long-term effects of cAMP on beta cell gene expression are less well understood. We used rat microarray analysis to compare the genome-wide gene expression response to short-term (2 hours) and long-term (16 hours) stimulations of the cAMP agonist forskolin in INS-1 insulinoma cells.
Project description:Addictive drugs including opioids activate signal transduction pathways that regulate gene expression in the brain. However, changes in CNS gene expression following morphine exposure are poorly understood. We studied the effect of short- and long-term morphine treatment on gene expression in the hypothalamus and pituitary using genome-wide DNA microarray and real-time reverse transcriptase polymerase chain reaction (RT-PCR) analyses. In the hypothalamus, we found that short-term morphine administration up-regulated (at least 2-fold) 39 genes and down-regulated six genes. Long-term morphine administration up-regulated 35 genes and down-regulated 51 hypothalamic genes. In the pituitary, we found that short-term morphine administration up-regulated (at least 2-fold) 110 genes and down-regulated 29 genes. Long-term morphine administration up-regulated 85 genes and down-regulated 37 pituitary genes. Strikingly, microarray analysis uncovered several genes involved in food intake (neuropeptide Y, agouti-related protein, and cocaine and amphetamine-regulated transcript) whose expression was strongly altered by morphine exposure in either the hypothalamus or pituitary. Subsequent RT-PCR analysis confirmed similar gene regulation of noteworthy genes in these regions. Finally, we found functional correlation between morphine-induced alterations in food intake and regulations of genes involved in this process. Changes in genes related to food intake may uncover new pathways related to some of the physiological effects of opioids. Keywords: Comparative treatment versus placebo
Project description:The retina is uniquely enriched in polyunsaturated fatty acids (PUFAs), which are primarily localized in cell membranes, where they govern membrane biophysical properties such as diffusion, permeability, domain formation, and curvature generation. During aging, alterations in lipid metabolism lead to reduced content of very long-chain PUFAs (VLC-PUFAs) in the retina, and this decline is associated with normal age-related visual decline and pathological age-related macular degeneration (AMD). ELOVL2 (Elongation of very-long-chain fatty acids-like 2) encodes a transmembrane protein that produces precursors to docosahexaenoic acid (DHA) and VLC-PUFAs, and methylation level of its promoter is currently one of the best predictors of chronological age. Here, we show that mice lacking ELOVL2-specific enzymatic activity (Elovl2C234W) have impaired contrast sensitivity and slower rod response recovery following bright light exposure. Short-term and long-term intravitreal supplementation with the direct product of ELOVL2, 24:5n-3, in aged animals significantly improved visual function and reduced accumulation of ApoE and C3d in sub-RPE deposits. At the molecular level, the gene expression pattern observed in retinas supplemented with 24:5n-3 exhibited a partial rejuvenation profile, including decreased expression of aging-related genes and a transcriptomic signature of younger retina. Finally, we present the first human genetic data showing significant association of two variants in the ELOVL2 locus with the onset of intermediate AMD, underlying the translational significance of our findings. In sum, our study identifies novel therapeutic opportunities and defines ELOVL2 as a promising target for interventions aimed at preventing age-related vision loss.
Project description:Addictive drugs including opioids activate signal transduction pathways that regulate gene expression in the brain. However, changes in CNS gene expression following morphine exposure are poorly understood. We studied the effect of short- and long-term morphine treatment on gene expression in the hypothalamus and pituitary using genome-wide DNA microarray and real-time reverse transcriptase polymerase chain reaction (RT-PCR) analyses. In the hypothalamus, we found that short-term morphine administration up-regulated (at least 2-fold) 39 genes and down-regulated six genes. Long-term morphine administration up-regulated 35 genes and down-regulated 51 hypothalamic genes. In the pituitary, we found that short-term morphine administration up-regulated (at least 2-fold) 110 genes and down-regulated 29 genes. Long-term morphine administration up-regulated 85 genes and down-regulated 37 pituitary genes. Strikingly, microarray analysis uncovered several genes involved in food intake (neuropeptide Y, agouti-related protein, and cocaine and amphetamine-regulated transcript) whose expression was strongly altered by morphine exposure in either the hypothalamus or pituitary. Subsequent RT-PCR analysis confirmed similar gene regulation of noteworthy genes in these regions. Finally, we found functional correlation between morphine-induced alterations in food intake and regulations of genes involved in this process. Changes in genes related to food intake may uncover new pathways related to some of the physiological effects of opioids. Keywords: Comparative treatment versus placebo 8 samples analyzed: 4 from hypothalamus (2 biological replicates and 2 dye swaps) and 4 from pituitary (2 biological replicates and 2 dye swaps) 8 samples analyzed: 4 from hypothalamus short term treatment (2 biological replicates and 2 dye swaps) and 4 hypothalamus long term treatment (2 biological replicates and 2 dye swaps)
Project description:Analysis of transcriptome profile response to short-, middle- and long-term high light stress, as well as the transcriptome profile of recovery from high light stress.
Project description:RNA-Seq analysis was used to study the profile of exhausted Tcells and how anti-PD-L1 treatment changed the properties of these cells short term & long term after treatment
Project description:In this study, we examined the effects of VOCs exposure in humans on gene expression using microarray analysis. We recruited participants who had short-term exposure, long-term exposure, or no exposure. We then analyzed changes in gene expression in blood samples from these participants. A total of 866 genes were upregulated, while 366 genes were downregulated in the short-term exposure group. Similarly, in the long-term exposure group, a total of 852 and 480 genes were up- or downregulated, respectively. Hierarchical clustering analysis was used to divide the clustered genes into nine clusters to investigate the expression of variations in accordance with the exposure period. Further research is required to determine the time-dependent effects of VOCs on epigenetic regulation of gene expression. Gene expression of mRNA in human blood samples (IRB #AS 14039) divided into three groups: control (unexposed workers; n = 12), short-term exposure (workers exposed to VOCs for less than 10 years; n = 12), and long-term exposure (workers exposed to VOCs for more than 10 years; n = 12) was experimented by microarray analysis after exposure to VOCs