Methamphetamine-induced changes in myocardial gene transcription are sex-dependent

Abstract Background Prior work demonstrated that female rats (but not their male littermates) exposed to methamphetamine become hypersensitive to myocardial ischemic injury. Importantly, this sex-dependent effect persists following 30 days of subsequent abstinence from the drug, suggesting that it may be mediated by long term changes in gene expression that are not rapidly reversed following discontinuation of methamphetamine use. The goal of the present study was to determine whether methamphetamine induces sex-dependent changes in myocardial gene expression and whether these changes persist following subsequent abstinence from methamphetamine. Results Methamphetamine induced changes in the myocardial transcriptome were significantly greater in female hearts than male hearts both in terms of the number of genes affected and the magnitude of the changes. The largest changes in female hearts involved genes that regulate the circadian clock (Dbp, Per3, Per2, BMal1, and Npas2) which are known to impact myocardial ischemic injury. These genes were unaffected by methamphetamine in male hearts. All changes in gene expression identified at day 11 returned to baseline by day 30. Conclusions These data demonstrate that female rats are more sensitive than males to methamphetamine-induced changes in the myocardial transcriptome and that methamphetamine does not induce changes in myocardial transcription that persist long term after exposure to the drug has been discontinued.

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Epigenetic Regulatory Dynamics in Models of Methamphetamine-Use Disorder

Genes ◽

10.3390/genes12101614 ◽

2021 ◽

Vol 12 (10) ◽

pp. 1614

Author(s):

Subramaniam Jayanthi ◽

Michael T. McCoy ◽

Jean Lud Cadet

Keyword(s):

Gene Expression ◽

Brain Regions ◽

Reward Processing ◽

Post Translational Modifications ◽

Methamphetamine Use ◽

Underlying Mechanisms ◽

Induced Changes ◽

Methamphetamine Use Disorder ◽

Disease Exposure

Methamphetamine (METH)-use disorder (MUD) is a very serious, potentially lethal, biopsychosocial disease. Exposure to METH causes long-term changes to brain regions involved in reward processing and motivation, leading vulnerable individuals to engage in pathological drug-seeking and drug-taking behavior that can remain a lifelong struggle. It is crucial to elucidate underlying mechanisms by which exposure to METH leads to molecular neuroadaptive changes at transcriptional and translational levels. Changes in gene expression are controlled by post-translational modifications via chromatin remodeling. This review article focuses on the brain-region specific combinatorial or distinct epigenetic modifications that lead to METH-induced changes in gene expression.

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Gastric bypass in female rats lowers concentrated sugar solution intake and preference without affecting brief-access licking after long-term sugar exposure

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00240.2019 ◽

2020 ◽

Vol 318 (5) ◽

pp. R870-R885

Author(s):

Kellie M. Hyde ◽

Ginger D. Blonde ◽

Marco Bueter ◽

Carel W. le Roux ◽

Alan C. Spector

Keyword(s):

Gastric Bypass ◽

Experimental Design ◽

Female Rats ◽

Sugar Solution ◽

High Concentrations ◽

Solution Intake ◽

Induced Changes ◽

Surgically Induced

In rodents, Roux-en-Y gastric bypass (RYGB) decreases intake of, and preference for, foods or fluids that are high in sugar. Whether these surgically induced changes are due to decreases in the palatability of sugar stimuli is controversial. We used RYGB and sham-operated (SHAM) female rats to test the influence of prolonged ingestive experience with sugar solutions on the motivational potency of these stimuli to drive licking in brief-access (BA) tests. In experiment 1, RYGB attenuated intake of, and caloric preference for, 0.3 M sucrose during five consecutive, 46-h two-bottle tests (TBTs; sucrose). A second series of TBTs (5 consecutive, 46-h tests) with 1.0 M sucrose revealed similar results, except fluid preference for 1.0 M sucrose also significantly decreased. Before, between, and after the two series of TBTs, two sessions of BA tests (30 min; 10-s trials) with an array of sucrose concentrations (0 and 0.01–1.0 M) were conducted. Concentration-dependent licking and overall trial initiation did not differ between surgical groups in any test. In a similar experimental design in a second cohort of female rats, 0.6 and 2.0 M glucose (isocaloric with sucrose concentrations in experiment 1) were used in the TBTs; 0 and 0.06-2.0 M glucose were used in the BA tests. Outcomes were similar to those for experiment 1, except RYGB rats initiated fewer trials during the BA tests. Although RYGB profoundly affected intake of, and caloric preference for, sugar solutions and, with high concentrations, fluid preference, RYGB never influenced the motivational potency of sucrose or glucose to drive concentration-dependent licking in BA tests.

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371 CYTOKINE-INDUCED CHANGES IN GENE EXPRESSION IN SHORT-TERM CULTURES DO NOT FULLY MIMIC ABERRANT EXPRESSION IN OSTEOARTHRITIS: ADVANTAGES OF LONG-TERM CULTURES

Osteoarthritis and Cartilage ◽

10.1016/s1063-4584(09)60393-9 ◽

2009 ◽

Vol 17 ◽

pp. S196

Author(s):

K. Hashimoto ◽

M.B. Goldring ◽

H.I. Roach

Keyword(s):

Gene Expression ◽

Short Term ◽

Aberrant Expression ◽

Induced Changes

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Regulation of pituitary inhibin/activin subunits and follistatin gene expression by GnRH in female rats

Journal of Endocrinology ◽

10.1530/joe-10-0485 ◽

2011 ◽

Vol 210 (1) ◽

pp. 71-79 ◽

Cited By ~ 7

Author(s):

Petra Popovics ◽

Zoltan Rekasi ◽

Alan J Stewart ◽

Magdolna Kovacs

Keyword(s):

Gene Expression ◽

Mrna Level ◽

Inhibin B ◽

Female Rats ◽

Pituitary Cells ◽

Mrna Levels ◽

Short Term ◽

Α Subunit ◽

Long Term Treatment

Pituitary inhibin B, activin B, and follistatin are local regulators of FSH. Activin B is a homodimeric molecule (βB–βB), while inhibin B contains an α and a βB subunit. The regulation of gene expression of α, βB, and follistatin by local and endocrine hormones was examined in pituitaries from female rats and in perifused pituitary cells by RT-PCR. Ovariectomy (OVX) induced an elevation in the mRNA level of α and βB subunits and follistatin. Short-term (4 h) treatment of pituitary cells with GnRH decreased both the inhibin α and the inhibin/activin βB subunit mRNA levels, while long-term treatment (20 h) with 100 nM GnRH stimulated the expression of both subunits. In contrast, the mRNA level of follistatin was elevated after the short-term GnRH treatment. Long-term exposure of pituitary cells to estradiol and inhibin B suppressed the mRNA expression of βB and had no effect on the expression of α subunit and follistatin. Our results demonstrate that the increased expressions of inhibin/activin subunits and follistatin in the post-OVX period can be induced by the lack of gonadal negative feedback, resulting in a high GnRH environment in the pituitary. This study reports for the first time that GnRH administered in high doses and for a long period stimulates the gene expression of inhibin/activin subunits and thereby may contribute to the stimulatory effect of OVX on the expression of these genes.

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Pathogenesis of Acute Myeloid Leukemia: In Vitro Studies Using Primary Human Cells.

Blood ◽

10.1182/blood.v112.11.2264.2264 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2264-2264

Author(s):

Anmaar Abdul-Nabi ◽

Enas R Yassin ◽

Akiko Takeda ◽

Nabeel R. Yaseen

Keyword(s):

Gene Expression ◽

Acute Myeloid Leukemia ◽

Transcription Factors ◽

Myeloid Leukemia ◽

Human Peripheral Blood ◽

Gene Profiling ◽

Number Of Genes ◽

Acute Myeloid ◽

Time Point

Abstract Many cases of acute myeloid leukemia (AML) are associated with non-random chromosomal rearrangements and most of these result in fusions involving retinoic acid receptor α (RARα), CBF transcription factors, MLL, and nucleoporins. Here, we report the effects of key members of these four major groups of AML-associated chimeric fusion proteins on differentiation, proliferation, self-renewal and gene expression in primary human CD34+ hematopoietic cells. We expressed the PML-RARα, AML1-ETO, MLL-AF9 and NUP98-HOXA9 fusion genes in human peripheral blood CD34+ cells by retroviral transduction and compared them to cells transduced with empty vector. By colony forming assays, morphological examination and flow cytometric immunophenotyping we found that PML-RARα causes some degree of myeloid differentiation block. AML1-ETO had no obvious effect on differentiation, while MLL-AF9 and NUP98-HOXA9 caused a block in both myeloid and erythroid differentiation. All fusion oncoproteins, except PML-RARα, induced dramatic long-term proliferation in liquid culture and a marked increase in the numbers of primitive long-term culture-initiating cells (LTC-ICs). In order to understand the molecular basis of these effects, gene expression profiling was performed for each fusion gene by oligonucleotide microarray analysis at 3 different time points (6 h, 3 days, and 8 days post transduction). At the 6 h time point both AML1-ETO and PML-RARα caused extensive changes in gene expression with a predominance of downregulated genes. The number of genes dysregulated by AML1-ETO and PML-RARα decreased dramatically at the 3-day time point. These data are consistent with the fact that these two oncoproteins are DNA-binding transcription factors that are known to repress transcription. In contrast, MLL-AF9 and NUP98-HOXA9 altered the expression of fewer genes at the 6 h time point with a preponderance of upregulated genes; at the 3 day time point, the number of genes dysregulated by NUP98-HOXA9 and MLL-AF9 increased. These findings suggest that NUP98-HOXA9 and MLL-AF9 may have delayed effects that are not due to direct transcriptional regulation. Homeobox transcription factors were upregulated by both MLL-AF9 and NUP98-HOXA9, but not by either AML1-ETO or PML-RARα. The results of the biological assays and gene profiling show marked similarities between NUP98-HOXA9 and MLL-AF9, and suggest that they transform cells by similar pathways that are different from those used by AML1-ETO and PML-RARα.

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Effect of hypoxia on gene expression by human hepatocytes (HepG2)

Physiological Genomics ◽

10.1152/physiolgenomics.00104.2002 ◽

2003 ◽

Vol 12 (3) ◽

pp. 195-207 ◽

Cited By ~ 48

Author(s):

Larry A. Sonna ◽

Michael L. Cullivan ◽

Holly K. Sheldon ◽

Richard E. Pratt ◽

Craig M. Lilly

Keyword(s):

Gene Expression ◽

Hepg2 Cells ◽

Cdna Array ◽

Hypoxic Stress ◽

Control Room ◽

Significant Component ◽

Oligonucleotide Arrays ◽

Number Of Genes ◽

Late Generation ◽

Induced Changes

The full extent to which hypoxia produces gene expression changes in human cells is unknown. We used late-generation oligonucleotide arrays to catalog hypoxia-induced changes in gene expression in HepG2 cells. Five paired sets of cultures were subjected to either control (room air-5% CO2) or hypoxic (1% O2-5% CO2) conditions for 24 h, and RNA was analyzed on an Affymetrix cDNA array containing ∼12,600 sequences. A statistically significant change in expression was shown by 2,908 sequences (1,255 increased and 1,653 decreased). The observed changes were highly concordant with published literature on hypoxic stress but showed relatively little overlap (12–22%) with changes in gene expression that have been reported to occur after heat stress in other systems. Of note, of these 2,908 sequences, only 387 (213 increased and 174 decreased) both exhibited changes in expression of twofold or greater and were highly expressed in at least three of the five experiments. We conclude that the effect of hypoxia on gene expression by HepG2 cells is broad, has a significant component of downregulation, and includes a relatively small number of genes whose response is truly independent of cell and stress type.

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Short- and long-term effects of olanzapine on food intake and hypothalamic gene expression in female rats

Appetite ◽

10.1016/j.appet.2011.05.247 ◽

2011 ◽

Vol 57 ◽

pp. S35

Author(s):

R.H. Purcell ◽

E.R. Ewald ◽

K. Volk ◽

B. Sun ◽

N.C. Liang ◽

...

Keyword(s):

Gene Expression ◽

Food Intake ◽

Female Rats ◽

Long Term Effects ◽

Short And Long Term

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PRIMING OF MICROGLIA ACTIVITY INCREASES SUSCEPTIBILITY TO DEPRESSION-LIKE BEHAVIORS

Innovation in Aging ◽

10.1093/geroni/igz038.359 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S95-S95

Author(s):

Tal Frolinger ◽

Umar Iqbal ◽

Giulio M Pasinetti

Keyword(s):

Gene Expression ◽

Depression And Anxiety ◽

Toll Like Receptor 4 ◽

Immune Priming ◽

Symptoms Of Depression ◽

Tlr4 Gene ◽

Induced Changes ◽

Increased Activity

Abstract This study investigates the role of microglia activity in stress-induced depression and anxiety and the mechanisms associated with the role of certain microbiome derived anti-inflammatory polyphenols in attenuating stress-induced microglia immune priming and symptoms of depression. We implemented a chronic unpredictable stress (CUS) paradigm to exhibit priming of microglia innate immunity in the context of the onset of depression and anxiety phenotypes. Mechanistic studies related to prophylactic treatment using dietary microbiome derived polyphenols were also investigated in this model. Depression and anxiety phenotypes, gene expression in microglia and protein expression in the cortex of mice were measured following a primary exposure to short-term unpredictable stress (US) followed by CUS. We examined the long-term, persistent CUS induced changes at 4-weeks of post-stress rest following a secondary US exposure. We found depression phenotypes resulted from US only following exposure to CUS. This was accompanied by an increase and persistent upregulation of toll-like receptor 4 (TLR4), RAGE, and HMGB1 gene expression in isolated cortical microglia. Priming by CUS also amplified gene expression of IL-1β in microglia and protein IL-1β in the cerebral cortex following US re-exposure. Increased activity of NF-kB was also noted in the period following CUS. Furthermore, polyphenol treatment prevented stress-induced phenotypes, upregulation of HMGB1, IL-1B, and TLR4 gene expression, as well as upregulation of IL-1β and NF-kB. The study suggests that latent activity of the TLR4-NFkB-IL1β pathway contributes to immune priming and increases susceptibility to depression-like behaviors. Anti-depressant effects of polyphenols may result from their ability to attenuate microglia priming.

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