scholarly journals Long-term consequences of chronic fluoxetine exposure on the expression of myelination-related genes in the rat hippocampus

2015 ◽  
Vol 5 (9) ◽  
pp. e642-e642 ◽  
Author(s):  
Y Kroeze ◽  
D Peeters ◽  
F Boulle ◽  
D L A van den Hove ◽  
H van Bokhoven ◽  
...  
Keyword(s):  
Gene Expression ◽  
Psychiatric Disorders ◽  
Neurotrophic Factor ◽  
Brain Connectivity ◽  
Adult Rats ◽  
Expression Of Genes ◽  
Chronic Fluoxetine ◽  
Long Term Consequences ◽  
Underlying Mechanisms

Abstract The selective serotonin reuptake inhibitor (SSRI) fluoxetine is widely prescribed for the treatment of symptoms related to a variety of psychiatric disorders. After chronic SSRI treatment, some symptoms remediate on the long term, but the underlying mechanisms are not yet well understood. Here we studied the long-term consequences (40 days after treatment) of chronic fluoxetine exposure on genome-wide gene expression. During the treatment period, we measured body weight; and 1 week after treatment, cessation behavior in an SSRI-sensitive anxiety test was assessed. Gene expression was assessed in hippocampal tissue of adult rats using transcriptome analysis and several differentially expressed genes were validated in independent samples. Gene ontology analysis showed that upregulated genes induced by chronic fluoxetine exposure were significantly enriched for genes involved in myelination. We also investigated the expression of myelination-related genes in adult rats exposed to fluoxetine at early life and found two myelination-related genes (Transferrin (Tf) and Ciliary neurotrophic factor (Cntf)) that were downregulated by chronic fluoxetine exposure. Cntf, a neurotrophic factor involved in myelination, showed regulation in opposite direction in the adult versus neonatally fluoxetine-exposed groups. Expression of myelination-related genes correlated negatively with anxiety-like behavior in both adult and neonatally fluoxetine-exposed rats. In conclusion, our data reveal that chronic fluoxetine exposure causes on the long-term changes in expression of genes involved in myelination, a process that shapes brain connectivity and contributes to symptoms of psychiatric disorders.

scholarly journals Coordinated multitissue transcriptional and plasma metabonomic profiles following acute caloric restriction in mice

2006 ◽  
Vol 27 (3) ◽  
pp. 187-200 ◽  
Author(s):  
Colin Selman ◽  
Nicola D. Kerrison ◽  
Anisha Cooray ◽  
Matthew D. W. Piper ◽  
Steven J. Lingard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Caloric Restriction ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Proton Nuclear Magnetic Resonance ◽  
Cellular Transport ◽  
Expression Of Genes ◽  
Transcriptional Changes

Caloric restriction (CR) increases healthy life span in a range of organisms. The underlying mechanisms are not understood but appear to include changes in gene expression, protein function, and metabolism. Recent studies demonstrate that acute CR alters mortality rates within days in flies. Multitissue transcriptional changes and concomitant metabolic responses to acute CR have not been described. We generated whole genome RNA transcript profiles in liver, skeletal muscle, colon, and hypothalamus and simultaneously measured plasma metabolites using proton nuclear magnetic resonance in mice subjected to acute CR. Liver and muscle showed increased gene expressions associated with fatty acid metabolism and a reduction in those involved in hepatic lipid biosynthesis. Glucogenic amino acids increased in plasma, and gene expression for hepatic gluconeogenesis was enhanced. Increased expression of genes for hormone-mediated signaling and decreased expression of genes involved in protein binding and development occurred in hypothalamus. Cell proliferation genes were decreased and cellular transport genes increased in colon. Acute CR captured many, but not all, hepatic transcriptional changes of long-term CR. Our findings demonstrate a clear transcriptional response across multiple tissues during acute CR, with congruent plasma metabolite changes. Liver and muscle switched gene expression away from energetically expensive biosynthetic processes toward energy conservation and utilization processes, including fatty acid metabolism and gluconeogenesis. Both muscle and colon switched gene expression away from cellular proliferation. Mice undergoing acute CR rapidly adopt many transcriptional and metabolic changes of long-term CR, suggesting that the beneficial effects of CR may require only a short-term reduction in caloric intake.

scholarly journals Changes in the Multipotent Stromal Mesenchymal Cells from the Bone Marrow of the Patients with Hematological Diseases in Debut and after the Treatment

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5014-5014
Author(s):  
Irina N. Shipounova ◽  
Nataliya A. Petinati ◽  
Nina J. Drize ◽  
Aminat A. Magomedova ◽  
Ekaterina A. Fastova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Stromal Cells ◽  
Myeloid Leukemia ◽  
Marker Gene ◽  
Malignant Cells ◽  
Hematopoietic Stem ◽  
Stromal Microenvironment ◽  
Expression Of Genes

Introduction. Stromal microenvironment of the bone marrow (BM) is essential for normal hematopoiesis; the very same cells are involved in the interaction with the leukemic stem cells. The aim of the study was to reveal the alterations in stromal microenvironment of patients in debut and after the therapy using multipotent mesenchymal stromal cells (MSC) as a model. Methods. MSC of patients with acute myeloid leukemia (AML, N=32), acute lymphoblastic leukemia (ALL, N=20), chronic myeloid leukemia (CML, N=19), and diffuse large B-cell lymphoma without BM involvement (DLBCL, N=17) were isolated by standard method from the patients' BM. Each BM sample was acquired during diagnostic aspiration after the informed signed consent was obtained from the patient. Groups of BM donors comparable by age and gender were used as controls for each nosology. Gene expression was analyzed with real-time RT-PCR. The significance of differences was evaluated with Mann-Whitney U-test. Results. The results of gene expression analysis are summarized in Table. The expression of genes regulating hematopoietic stem and precursor cells (JAG1, LIF, IL6) was significantly upregulated in MSC of the patients in debut, except for DLBCL. The latter was characterized with upregulation of osteogenic marker gene SPP1 and downregulation of FGFR1 gene. The upregulation of the expression of genes regulating proliferation of stromal cells (PDGFRA, FGFR1) and adipogenic marker gene (PPARG) was common for AML and CML. Both acute leukemias were characterized by the upregulation of genes associated with inflammation and regulation of hematopoietic precursors (CSF1, IL1B, IL1BR1) and by the downregulation of chondrogenic differentiation marker gene (SOX9). CML and DLBCL demonstrated the upregulation of FGFR2. BM of the DLBCL patients did not contain any malignant cells; nevertheless, stromal precursors from the BM were significantly affected. This indicates the distant effects of DLBCL malignant cells on the patients' BM. Myeloid malignancies seem to affect MSC more profoundly then lymphoid ones. Effect of leukemic cells on stromal microenvironment in case of myeloid leukemia was more pronounced. The treatment significantly affected gene expression in MSC of patients. In all studied nosologies the IL6 gene expression was upregulated, which may reflect the inflammation processes ongoing in the organism. The expression of LIF was upregulated and ICAM1, downregulated in MSCs of AML, ALL, and CML patients. In the MSC of patients with AML, who had received the highest doses of cytostatic drugs to achieve remission, a significant decrease in the expression of most studied genes was found. In patients with ALL with long-term continuing treatment in combination with lower doses of drugs, IL1B expression was increased, while the decrease in expression was detected for a number of genes regulating hematopoietic stem cells (SDF1, TGFB1), differentiation and proliferation (SOX9, FGFR1, FGFR2). Treatment of CML patients is based on tyrosine kinase inhibitors in doses designed for long-term use, and is less damaging for MSC. The upregulation of TGFB1, SOX9, PDGFRA genes and downregulation of IL1B gene was revealed. MCS of DLBCL patients, unlike the other samples, were analyzed after the end of treatment. Nevertheless, significant upregulation of IL8 and FGFR2 genes was found. Thus, both the malignant cells and chemotherapy affect stromal precursor cells. The changes are not transient; they are preserved for a few months at least. MSCs comprise only a minor subpopulation in the BM in vivo. When expanded in vitro, they demonstrate significant changes between groups of patients and healthy donors. Conclusions. Leukemia cells adapt the stromal microenvironment. With different leukemia, the same changes are observed in the expression of genes in MSC. MSC of patients with acute forms have a lot of changes which coincide among these two diseases. MSC of AML patients are most affected both in debut and after the therapy. Treatment depends on the nosology and in varying degrees changes the MSC. This work was supported by the Russian Foundation for Basic Research, project no. 17-00-00170. Disclosures Chelysheva: Novartis: Consultancy, Honoraria; Fusion Pharma: Consultancy. Shukhov:Novartis: Consultancy; Pfizer: Consultancy. Turkina:Bristol Myers Squibb: Consultancy; Novartis: Consultancy, Speakers Bureau; Pfizer: Consultancy; Novartis: Consultancy, Speakers Bureau; fusion pharma: Consultancy.

scholarly journals From egg to embryo: a peripatetic journey

Reproduction ◽  
2005 ◽  
Vol 130 (6) ◽  
pp. 825-828 ◽  
Author(s):  
Richard M Schultz
Keyword(s):  
Gene Expression ◽  
Assisted Reproductive Technologies ◽  
Egg Quality ◽  
Reproductive Technologies ◽  
Molecular Signature ◽  
High Quality ◽  
Long Term Consequences ◽  
The Uk ◽  
Effect Gene

The recent surge of interest in oocyte development has been spurred in large part by the increasing implementation of assisted reproductive technologies (ART) to treat human infertility. What is becoming apparent is that ‘egg quality’ is a primary factor in the success of ART (Sauer 1998), and yet we know virtually nothing about the molecular signature of a ‘high quality’ oocyte, i.e., an oocyte that is capable of maturing, being fertilized and supporting development to term. We are gaining marked insights, however, into how sperm activate eggs and the changes in gene expression that accompany preimplantation development. Nevertheless, embryo culture is known to effect gene expression (Rinaudo & Schultz 2004), the long-term consequences of which are only recently being unmasked. This review will briefly highlight these topics that were presented during the Biennial Joint Meeting of the UK Fertility Societies at Warwick University in April 2005.

Prolactin decreases expression of Runx2, osteoprotegerin, and RANKL in primary osteoblasts derived from tibiae of adult female rats

2008 ◽  
Vol 86 (5) ◽  
pp. 240-248 ◽  
Author(s):  
Narattaphol Charoenphandhu ◽  
Jarinthorn Teerapornpuntakit ◽  
Methajit Methawasin ◽  
Kannikar Wongdee ◽  
Kanogwun Thongchote ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Bone Cells ◽  
Nuclear Factor Κb ◽  
Clinical Findings ◽  
Female Rats ◽  
Adult Rats ◽  
Expression Of Genes ◽  
Primary Osteoblasts ◽  
Underlying Mechanisms

Hyperprolactinemia caused by physiological or pathological conditions, such as those occurring during lactation and prolactinoma, respectively, results in progressive osteopenia. The underlying mechanisms, however, are controversial. Prolactin (PRL) may directly attenuate the functions of osteoblasts, since these bone cells express PRL receptors. The present study therefore aimed to investigate the effects of PRL on the expression of genes related to the osteoblast functions by using quantitative real-time PCR technique. Herein, we used primary osteoblasts that were derived from the tibiae of adult rats and displayed characteristics of differentiated osteoblasts, including in vitro mineralization. Osteoblasts exposed for 48 h to 1000 ng/mL PRL, but not to 10 or 100 ng/mL PRL, showed decreases in the mRNA expression of Runx2, osteoprotegerin (OPG), and receptor activator of nuclear factor κB ligand (RANKL) by 60.49%, 72.74%, and 87.51%, respectively. Nevertheless, PRL did not change the RANKL/OPG ratio, since expression of OPG and RANKL were proportionally decreased. These concentrations of PRL had no effect on the mRNA expression of osteocalcin and osteopontin, nor on mineralization. High pathologic concentrations of PRL (1000 ng/mL) may downregulate expression of genes that are essential for osteoblast differentiation and functions. The present results explained the clinical findings of hyperprolactinemia-induced bone loss.

285 VIABILITY AND GENE EXPRESSION OF MESENCHYMAL STEM CELLS CRYOPRESERVED WITH DIFFERENT CRYOPROTECTANTS

2008 ◽  
Vol 20 (1) ◽  
pp. 222 ◽  
Author(s):  
M. K. Kim ◽  
S. A. Ock ◽  
B. G. Jeon ◽  
J. H. Cho ◽  
G. J. Rho
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Expression Patterns ◽  
Long Term Storage ◽  
Expression Of Genes ◽  
Cell Tissue ◽  
Fetal Bovine

Long-term storage of stem cells with self-renewal plays a pivotal role in cell tissue engineering, which could be a novel option for improving regenerative diseases. However, the choice of a selective cryoprotectant is still to be addressed. Dimethyl sulfoxide (DMSO), which in current practice is the most widely used as a cryoprotectant for cell freezing, is known to have toxic side effects (Wang et al. 2007 Cryobiology 55, 60–65). In this study, therefore, the effect of two different cryoprotectants, used alone or in combination, on frozen–thawed porcine mesenchymal stem cells (MSCs) was investigated by evaluating their viability, apoptosis, and gene expression patterns. MSCs isolated from bone marrow were cultured in advanced Dulbecco's modified Eagle medium (ADMEM) supplemented with 10% fetal bovine serum (FBS) and characterized by the expression of alkaline phosphatase (AP) activity and cell-surface antigen profiles (CD105 as positive, CD45 and CD133 as negative markers). Subconfluent cultures of MSCs (1 � 106 cells mL–1) at 4–5 passages were equilibrated in different cryoprotectants: (1)ADMEM supplemented with 10% DMSO, (2) ADMEM supplemented with 1.5 m ethylene glycol (EG), and (3) ADMEM supplemented with 0.75 m EG and 5% DMSO, and frozen in a programmable freezer. The straws were cooled at –4�C min–1 from 25�C to –7�C. After being seeded, the straws were further cooled to –35�C at a –0.6�C min–1 ramp rate, and then immediately plunged into LN2 and stored at least a week. After thawing at 37�C in a water bath, viability and apoptosis of cells were analyzed by flow cytometry using an In Situ Cell Death Detection kit (Roche, Mannheim, Germany). Expression of HSP70, Nanog, and β-actin was analyzed by Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR), and compared to that of non-cryopreserved MSCs. Doubling time of cryopreserved MSCs was higher than for non-cryopreserved MSCs. There were no significant differences among cryopreserved groups. The rates of viability and apoptosis of non-cryopreserved MSCs (91% and 4.71%, respectively) was significantly (P < 0.05) higher than for MSCs cryopreserved with 10% DMSO, 1.5 m EG, or the 0.75 m EG and 5% DMSO mixture (71.78% and 3.45%, 70.09% and 3.22%, 68.97% and 2.42%, respectively), but the rates among different cryopreserved treatments did not differ. After thawing, expression of HSP70, Nanog, and β-actin in cryopreserved MSCs showed patterns similar to those of non-cryopreserved MSCs. In conclusion, the present study indicates that EG is an alternative cryoprotectant for cryopreservation of porcine MSCs. Further studies are needed to evaluate the possible effects on the expression of genes related to viability and apoptosis in MSCs cryopreserved with different cryoprotectants.

52 Ovarian Follicular Profiling of High- and Low-immunocrit Gilts on Postnatal Day 14

2021 ◽  
Vol 99 (Supplement_1) ◽  
pp. 150-151
Author(s):  
Brianna M Lynnes ◽  
Robert A Cushman ◽  
Jeremy R Miles ◽  
William T Oliver ◽  
Frank F Bartol ◽  
...  
Keyword(s):  
Gene Expression ◽  
Birth Weight ◽  
Equal Opportunity ◽  
Follicular Development ◽  
Ovarian Follicles ◽  
Neonatal Piglets ◽  
Somatic Tissues ◽  
Long Term Consequences ◽  
Follicular Dynamics

Abstract Colostrum intake by neonatal piglets can be measured using the immunoglobulin immunocrit assay (iCrit). Lactocrine effects occur when maternally derived, milk-borne bioactive factors are transferred to the neonatal circulation with consumption of colostrum during nursing and affect development of somatic tissues, which can have long-term consequences in adulthood. Lactocrine deficiency, indicated by low neonatal iCrit, altered uterine gene expression and reduced fecundity in adult, neonatally lactocrine-deficient gilts. Litter size in pigs is dependent on both ovarian and uterine function. It was hypothesized that lactocrine deficiency affects development of ovarian follicles in gilts. The objective was to determine the number of primordial, primary, and secondary follicles in ovaries of gilts with high (12% ± 0.5; n = 10) or low (1.9% ± 0.4; n = 10) iCrit, determined on postnatal day (PND) 1 after birth. Paired high- and low-iCrit gilts were chosen from the same litters (birth weight; 3.1 ± 0.2 lbs). On PND 14, ovaries were collected and histological sections prepared (3 sections per animal; 30–150 µm apart). Ovarian follicles in each section were staged and the number of follicles in each category were quantified and subjected to ANOVA. Total number of ovarian follicles did not differ with iCrit (P = 0.55; 1,370.6 ± 147.8 follicles per section). The proportion of primordial, primary, and secondary follicles was 89.6 ± 1.15%, 7.7 ± 0.87%, 2.7 ± 0.51%, respectively. The number of primordial (P = 0.55), primary (P = 0.64), and secondary (P = 0.93) follicles did not differ with iCrit. Results indicate that ovarian follicular development of neonatal gilts is not sensitive to immunocrit status. Although lactocrine deficiency did not influence the ovarian follicular profile at PND 14, it remains unknown whether lactocrine programming alters ovarian follicular dynamics in neonatally lactocrine-deficient adults. USDA is an equal opportunity provider and employer.

scholarly journals Mechanisms of Fetal Programming in Hypertension

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
John Edward Jones ◽  
Julie A. Jurgens ◽  
Sarah A. Evans ◽  
Riley C. Ennis ◽  
Van Anthony M. Villar ◽  
...  
Keyword(s):  
Birth Weight ◽  
Fetal Programming ◽  
Intrauterine Growth Restriction ◽  
Intrauterine Growth ◽  
Fetal Survival ◽  
Nephron Endowment ◽  
Developmental Program ◽  
Expression Of Genes ◽  
Underlying Mechanisms

Events that occur in the early fetal environment have been linked to long-term health and lifespan consequences in the adult. Intrauterine growth restriction (IUGR), which may occur as a result of nutrient insufficiency, exposure to hormones, or disruptions in placental structure or function, may induce the fetus to alter its developmental program in order to adapt to the new conditions. IUGR may result in a decrease in the expression of genes that are responsible for nephrogenesis as nutrients are rerouted to the development of more essential organs. Fetal survival under these conditions often results in low birth weight and a deficit in nephron endowment, which are associated with hypertension in adults. Interestingly, male IUGR offspring appear to be more severely affected than females, suggesting that sex hormones may be involved. The processes of fetal programming of hypertension are complex, and we are only beginning to understand the underlying mechanisms.

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