scholarly journals Kainate-evoked modulation of gene expression in rat brain.

1997 ◽  
Vol 44 (4) ◽  
pp. 781-789 ◽  
Author(s):  
B Kaminska ◽  
R K Filipkowski ◽  
I W Biedermann ◽  
D Konopka ◽  
D Nowicka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cellular Localization ◽  
Neuronal Cell Death ◽  
Gene Expression Pattern ◽  
Neuronal Cell ◽  
Mrna Levels ◽  
Late Gene Expression ◽  
Adult Rats ◽  
Gene Expression Response ◽  
Spatio Temporal

Kainate is a glutamate analog that produces neuronal excitation resulting in seizures within hours following its intraperitoneal injection into adult rats. Then, at 2-3 days after the treatment, neurodegeneration of apoptotic character can be observed in limbic system. As a consequence, plastic reorganization and glial reactivation phenomena occur. These physiological and pathological responses are reflected by specific changes in gene expression, that can be dissected according to their spatio-temporal patterns. The early phase of gene expression observed in all hippocampal subfields appears to reflect a sudden burst of spiking activity. Changes in mRNA levels restricted to dentate gyrus are suggestive of a link to neuronal plasticity. The late gene expression response implies its correlation either to neuronal cell death or glial reactivation, depending on cellular localization of gene products. Thus analysis of the temporal and spatial gene expression pattern in the hippocampus after kainate treatment may provide clues revealing specific phenomena to which gene expression could be attributed.

scholarly journals Cerebral Ischemia Causes Dysregulation of Synaptic Adhesion in Mouse Synaptosomes

2007 ◽  
Vol 28 (1) ◽  
pp. 99-110 ◽  
Author(s):  
Willard J Costain ◽  
Ingrid Rasquinha ◽  
Jagdeep K Sandhu ◽  
Peter Rippstein ◽  
Bogdan Zurakowski ◽  
...  
Keyword(s):  
Cell Death ◽  
Cerebral Ischemia ◽  
Adhesion Molecules ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Artery Occlusion ◽  
Synaptic Proteins ◽  
Mrna Levels ◽  
Neuronal Nuclei ◽  
Protein Levels

Synaptic pathology is observed during hypoxic events in the central nervous system in the form of altered dendrite structure and conductance changes. These alterations are rapidly reversible, on the return of normoxia, but are thought to initiate subsequent neuronal cell death. To characterize the effects of hypoxia on regulators of synaptic stability, we examined the temporal expression of cell adhesion molecules (CAMs) in synaptosomes after transient middle cerebral artery occlusion (MCAO) in mice. We focused on events preceding the onset of ischemic neuronal cell death (< 48 h). Synaptosome preparations were enriched in synaptically localized proteins and were free of endoplasmic reticulum and nuclear contamination. Electron microscopy showed that the synaptosome preparation was enriched in spheres (≈650 nm in diameter) containing secretory vesicles and postsynaptic densities. Forebrain mRNA levels of synaptically located CAMs was unaffected at 3 h after MCAO. This is contrasted by the observation of consistent downregulation of synaptic CAMs at 20 h after MCAO. Examination of synaptosomal CAM protein content indicated that certain adhesion molecules were decreased as early as 3 h after MCAO. For comparison, synaptosomal Agrn protein levels were unaffected by cerebral ischemia. Furthermore, a marked increase in the levels of p-Ctnnb1 in ischemic synaptosomes was observed. p-Ctnnb1 was detected in hippocampal fiber tracts and in cornu ammonis 1 neuronal nuclei. These results indicate that ischemia induces a dysregulation of a subset of synaptic proteins that are important regulators of synaptic plasticity before the onset of ischemic neuronal cell death.

Differential regulation of FSH and inhibin gene expression and synthesis by testosterone in immature and mature male rats

1993 ◽  
Vol 137 (1) ◽  
pp. 69-79 ◽  
Author(s):  
A. Perheentupa ◽  
M. Bergendahl ◽  
F. H. de Jong ◽  
I. Huhtaniemi
Keyword(s):  
Gene Expression ◽  
Combined Treatment ◽  
Male Rats ◽  
Mrna Levels ◽  
Partial Recovery ◽  
Β Subunit ◽  
Adult Rats ◽  
Testosterone Treatment ◽  
Subunit Mrna ◽  
Immature Rats

ABSTRACT Direct effects of testosterone on gonadotrophins at the pituitary level were studied in intact and castrated immature (age 10 days) and mature (70 days) male rats. Gonadotrophin-releasing hormone action was blocked by treatment with a potent GnRH antagonist, Ac-d-pClPhe-d-pClPhe-d-Trp-Ser-Tyr-d-Arg-Leu-Arg-Pro-d-Ala-NH2CH3COOH (Ant; Organon 30276; 1·0 mg/kg body weight per day) injected subcutaneously. Silicone elastomer capsules were used for the testosterone treatment. Both treatments commenced on the day of orchiectomy and lasted for 7 days. In adult male rats Ant treatment suppressed serum testosterone from 9·5 ± 2·5 (s.e.m.) nmol/l to below the limit of detection (< 0·10 nmol/l; P < 0·01), and the testosterone implants reversed the decrease. Treatment with Ant decreased the pituitary content of FSH-β subunit mRNA in intact and orchiectomized rats to 14% of their respective controls (P < 0·01). These levels were increased to 80–81% of controls (not significant) in both groups by combined treatment with testosterone and Ant. Orchiectomy alone increased FSH-β subunit mRNA by 202% (P < 0·01). In intact immature rats Ant treatment decreased the level of pituitary FSH-β subunit mRNA to 21% (P<0·01), and a partial recovery (P < 0·01) to 42% of controls was observed with combined Ant + testosterone treatment. In contrast, in orchiectomized immature rats, where ANT decreased FSH-β subunit levels to 48% of controls (P < 0·01), testosterone was able to reverse these mRNA levels completely (114% of controls). No evidence for the direct pituitary effects of testosterone were found in the mRNA of the common α or LH-β subunits. In adult rats, the testicular inhibin α and βA subunit mRNA levels were increased (P < 0·01) by Ant + testosterone compared with Ant-treated animals, but there were no differences in serum immunoreactive inhibin between any of the uncastrated adult groups. In intact immature rats, Ant + testosterone treatment increased (P < 0·01) inhibin βA subunit mRNA levels compared with controls and Ant-treated animals. Ant decreased the level of peripheral inhibin immunoreactivity from 8·3 ± 2·0 U/ml to 2·1 ± 0·4 U/ml (P < 0·01) and testosterone reversed it to 5·8 ± 0·6 U/ml (not significant). In conclusion, our observations indicated that testosterone is able to stimulate FSH gene expression and secretion directly in immature and adult rats, but the testosterone response is enhanced at both ages by orchiectomy, even more so in the immature rat. This may be explained by age differences in the contribution of testicular inhibin to the regulation of FSH synthesis and secretion at the pituitary level. Journal of Endocrinology (1993) 137, 69–79

scholarly journals Placental Expression of Bile Acid Transporters in Intrahepatic Cholestasis of Pregnancy

2021 ◽  
Vol 22 (19) ◽  
pp. 10434
Author(s):  
Edgar Ontsouka ◽  
Alessandra Epstein ◽  
Sampada Kallol ◽  
Jonas Zaugg ◽  
Marc Baumann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Intrahepatic Cholestasis ◽  
Gene Expression Pattern ◽  
Transport Systems ◽  
Transcriptional Level ◽  
Maternal Body Mass Index ◽  
Mrna Levels ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Related Condition ◽  
Cholestasis Of Pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-related condition characterized by increased maternal circulating bile acids (BAs) having adverse fetal effects. We investigated whether the human placenta expresses specific regulation patterns to prevent fetal exposition to harmful amounts of BAs during ICP. Using real-time quantitative PCR, we screened placentae from healthy pregnancies (n = 12) and corresponding trophoblast cells (n = 3) for the expression of 21 solute carriers and ATP-binding cassette transporter proteins, all acknowledged as BA- and/or cholestasis-related genes. The placental gene expression pattern was compared between healthy women and ICP patients (n = 12 each). Placental SLCO3A1 (OATP3A1) gene expression was significantly altered in ICP compared with controls. The other 20 genes, including SLC10A2 (ASBT) and EPHX1 (EPOX, mEH) reported for the first time in trophoblasts, were comparably abundant in healthy and ICP placentae. ABCG5 was undetectable in all placentae. Placental SLC10A2 (ASBT), SLCO4A1 (OATP4A1), and ABCC2 mRNA levels were positively correlated with BA concentrations in ICP. Placental SLC10A2 (ASBT) mRNA was also correlated with maternal body mass index. We conclude that at the transcriptional level only a limited response of BA transport systems is found under ICP conditions. However, the extent of the transcriptional response may also depend on the severity of the ICP condition and the magnitude by which the maternal BA levels are increased.

scholarly journals Identification of heterogenous nuclear ribonucleoproteins (hnRNPs) and serine- and arginine-rich (SR) proteins that induce human papillomavirus type 16 late gene expression and alter L1 mRNA splicing

2021 ◽  
Author(s):  
Chengyu Hao ◽  
Lijing Gong ◽  
Xiaoxu Cui ◽  
Johanna Jönsson ◽  
Yunji Zheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Papillomavirus ◽  
Sr Proteins ◽  
Mrna Splicing ◽  
Late Gene ◽  
Mrna Levels ◽  
Late Gene Expression ◽  
Human Papillomavirus Type 16 ◽  
Hnrnp Proteins ◽  
L1 And L2

AbstractWe have determined the effect of seven serine- and arginine-rich (SR) proteins and 15 heterogenous nuclear ribonucleoproteins (hnRNPs) on human papillomavirus type 16 (HPV16) late gene expression. Of the seven SR proteins analyzed here, SRSF1, SRSF3, and SRSF9 induced HPV16 late gene expression, and five of the SR proteins affected HPV16 L1 mRNA splicing. Of the 15 hnRNP proteins analyzed here, hnRNP A2, hnRNP F, and hnRNP H efficiently induced HPV16 late gene expression, and all of the hnRNPs affected HPV16 L1 mRNA levels or mRNA splicing. Thus, the majority of SR proteins and hnRNPs have the potential to regulate HPV16 L1 mRNA splicing. Strict control of the expression of the immunogenic L1 and L2 capsid proteins may contribute to the ability of HPV16 to cause persistence.

Uteroplacental insufficiency alters hepatic fatty acid-metabolizing enzymes in juvenile and adult rats

2001 ◽  
Vol 280 (1) ◽  
pp. R183-R190 ◽  
Author(s):  
Robert H. Lane ◽  
David E. Kelley ◽  
Elisa M. Gruetzmacher ◽  
Sherin U. Devaskar
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Female Rats ◽  
Mrna Levels ◽  
Adult Rats ◽  
Serum Triglycerides ◽  
Hepatic Fatty Acid ◽  
Malonyl Coa

Multiple adult morbidities are associated with intrauterine growth retardation (IUGR) including dyslipidemia. We hypothesized that uteroplacental insufficiency and subsequent IUGR in the rat would lead to altered hepatic fatty acid metabolism. To test this hypothesis, we quantified hepatic mRNA levels of acetyl-CoA carboxylase (ACC), carnitine palmitoyltransferase (CPTI), the β-oxidation-trifunctional protein (HADH), fasting serum triglycerides, and hepatic malonyl-CoA levels at different ages in control and IUGR rats. Fetal gene expression of all three enzymes was decreased. Juvenile gene expression of CPTI and HADH continued to be decreased, whereas gene expression of ACC was increased. Serum triglycerides were unchanged. A sex-specific response was noted in the adult rats. In males, serum triglycerides, hepatic malonyl-CoA levels, and ACC mRNA levels were significantly increased, and CPTI and HADH mRNA levels were significantly decreased. In contrast, the female rats demonstrated no significant changes in these variables. These results suggest that uteroplacental insufficiency leads to altered hepatic fatty acid metabolism that may contribute to the adult dyslipidemia associated with low birth weight.

Abstract P007: Cardiomyocyte Damage-Released Extracellular S100A1 Protein Promotes Regeneration of Infarcted Myocardium by Modulating Cardiac Fibroblast Function

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
David Rohde ◽  
Gang Qiu ◽  
Nicole Herzog ◽  
Hugo A Katus ◽  
Angelika Bierhaus ◽  
...  
Keyword(s):  
Gene Expression ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Gene Expression Pattern ◽  
Left Ventricular ◽  
Apical Region ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Human Cardiomyocytes

Background: Similar to heart muscle-specific creatinkinase (CK-MB), S100A1 protein is released from damaged human cardiomyocytes in response to myocardial infarction (MI). Since S100A1-knock out (SKO) mice display rapid post-MI onset of adverse myocardial remodeling and accelerated transition to heart failure, we assessed the hypothesis that ischemia-related release of S100A1 protein modulates myocardial regeneration. Methods and Results: After LAD ligation in C57/B6 mice, S100A1 serum levels peaked at 10 µg/ml 8 hours post-MI, precisely mirroring the time course previously observed in MI patients. RT-PCR analyses in post-MI whole heart samples revealed significantly lower I-CAM (−50%) and IL-10 (−75%) mRNA abundance as well as heightened Collagen-1 (+40%) and VEGF (+80%) expression in SKO vs. WT mice (p<0.05, n=6 in each group). Interestingly, injection of an S100A1-neutralizing antibody prior to MI in WT mice mimicked the abnormalities observed in post-ischemic SKO animals. To further elucidate extracellular S100A1 biological activity, cardiomyocytes, cardiac fibroblasts (CF), endothelial and smooth muscle cells were exposed to S100A1 in vitro . A rapid internalization of S100A1 was exclusively found in CF, resulting in a phosphorylation of ERK1/2, JNK, and p38 with subsequent activation of NF-kappaB as assessed by Western Blot (WB) and EMSA. RT-PCR and WB analyses revealed significant alterations in CF gene expression in response to S100A1, including an increase in I-CAM (3,5-fold) and IL-10 (20-fold) mRNA levels and diminished Col-1 (−80%) expression. Similar effects were observed after direct injection of S100A1 protein into the left ventricular apical region of WT mice in vivo (S100A1- vs. PBS-injection, n=6). In SKO mice, intraperitoneal application of S100A1 prior to MI largely normalized the adverse gene expression pattern towards WT animals. Conclusions: Our study provides first evidence for cardiomyocyte damage-released S100A1 to act as an endogenous mediator of post-MI inflammation and tissue repair. Considering today's unability to manipulate these molecular mechanisms, extracellular S100A1 might represent a promising target for future therapies of MI.

scholarly journals Effect of IGF-I and PDGF administered in vivo on the expression of osteoblast-related genes in old rats

2002 ◽  
Vol 174 (1) ◽  
pp. 63-70 ◽  
Author(s):  
H Tanaka ◽  
A Wakisaka ◽  
H Ogasa ◽  
S Kawai ◽  
CT Liang
Keyword(s):  
Gene Expression ◽  
Growth Factors ◽  
Mrna Expression ◽  
Combined Treatment ◽  
Mrna Levels ◽  
Adult Rats ◽  
Igf I ◽  
Old Rats ◽  
Osteoblast Markers ◽  
Marrow Ablation

In order to establish the cellular basis for using growth factors as possible therapeutic agents for the age-dependent deficit in bone formation activity, we examined the individual and combined effects of IGF-I and/or platelet-derived growth factor (PDGF) on the gene expression of osteoblast-related markers in male rats. The expression of osteoblast markers was examined in the femurs of adult and old rats following marrow ablation, which amplifies gene expression activity. The mRNA levels of collagen(alpha1) (I) (COLI), alkaline phosphatase (AP), osteopontin (OP) and osteocalcin (OC) were significantly lower in the old as compared with the adult rats. To determine whether growth factors can abolish the age-related deficits in mRNA expression in old bone, PDGF and/or IGF-I were infused directly into the right femur for 5 days following marrow ablation. The contralateral femur was infused with vehicle only and used as a control. PDGF stimulated the expression of OP mRNA in both adult and old rats, whereas COLI, AP and OC mRNAs were not affected. IGF-I infusion did not have a significant effect on mRNA expression in adult rats. In contrast, treatment with IGF-I significantly enhanced the mRNA levels of COLI, AP and OP in old rats. To examine whether the combination of both factors could affect the expression of osteoblast markers synergistically, PDGF and IGF-I were infused together. In adult bones, the combined treatment with PDGF and IGF-I caused a slight increase in the level of OP gene expression but no change in AP, OC or COLI genes. Although neither IGF-I nor PDGF alone was effective in stimulating the expression of OC, the combined treatment in old bones enhanced OC expression significantly. The expression of COLI, AP and OP was also stimulated, but the stimulation was no different from that of IGF-I alone. In PDGF plus IGF-I treatment with a high dose, no dose-response effects were observed. Within the limits of the present study, it is suggested that IGF-I and, to a much lesser extent, PDGF may partially restore the deficit in the expression of osteoblast markers in old bones, and that the combination of both factors is slightly better than IGF-I alone in stimulating OC expression.

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