Decreased Orexin Receptor 1 mRNA Expression in the Locus Coeruleus in Both Tau Transgenic rTg4510 and Tau Knockout Mice and Accompanying Ascending Arousal System Tau Invasion in rTg4510

2020 ◽  
pp. 1-16
Author(s):  
Ryan J. Keenan ◽  
Sara Oberrauch ◽  
Romke Bron ◽  
Cameron J. Nowell ◽  
Leesa M. Challis ◽  
...  
Keyword(s):  
Locus Coeruleus ◽  
Mrna Expression ◽  
Neurodegenerative Disorders ◽  
Clinical Evidence ◽  
Mrna Levels ◽  
Potential Mechanism ◽  
Receptor Mrna ◽  
Arousal System ◽  
Bidirectional Relationship ◽  
Similar Decrease

Background: Sleep/wake disturbances (e.g., insomnia and sleep fragmentation) are common in neurodegenerative disorders, especially Alzheimer’s disease (AD) and frontotemporal dementia (FTD). These symptoms are somewhat reminiscent of narcolepsy with cataplexy, caused by the loss of orexin-producing neurons. A bidirectional relationship between sleep disturbance and disease pathology suggests a detrimental cycle that accelerates disease progression and cognitive decline. The accumulation of brain tau fibrils is a core pathology of AD and FTD-tau and clinical evidence supports that tau may impair the orexin system in AD/FTD. This hypothesis was investigated using tau mutant mice. Objective: To characterize orexin receptor mRNA expression in sleep/wake regulatory brain centers and quantify noradrenergic locus coeruleus (LC) and orexinergic lateral hypothalamus (LH) neurons, in tau transgenic rTg4510 and tau–/– mice. Methods: We used i n situ hybridization and immunohistochemistry (IHC) in rTg4510 and tau–/– mice. Results: rTg4510 and tau–/– mice exhibited a similar decrease in orexin receptor 1 (OX1R) mRNA expression in the LC compared with wildtype controls. IHC data indicated this was not due to decreased numbers of LC tyrosine hydroxylase-positive (TH) or orexin neurons and demonstrated that tau invades TH LC and orexinergic LH neurons in rTg4510 mice. In contrast, orexin receptor 2 (OX2R) mRNA levels were unaffected in either model. Conclusion: The LC is strongly implicated in the regulation of sleep/wakefulness and expresses high levels of OX1R. These findings raise interesting questions regarding the effects of altered tau on the orexin system, specifically LC OX1Rs, and emphasize a potential mechanism which may help explain sleep/wake disturbances in AD and FTD.

scholarly journals Increased endothelin and endothelin receptor mRNA expression in polycystic kidneys of cpk mice.

1993 ◽  
Vol 4 (4) ◽  
pp. 1064-1072 ◽  
Author(s):  
T Nakamura ◽  
I Ebihara ◽  
M Fukui ◽  
S Osada ◽  
Y Tomino ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Transforming Growth Factor Beta ◽  
Proliferating Cell Nuclear Antigen ◽  
Transforming Growth Factor ◽  
Nuclear Antigen ◽  
Tnf Alpha ◽  
Mrna Levels ◽  
Tgf Beta ◽  
Receptor Mrna ◽  
Proliferating Cell

The renal mRNA levels of endothelin (ET)-1 and ET-3 and for ET receptors A and B were measured in the cystic kidneys of cpk/cpk mice at 1, 2, and 3 wk of age. At 1 wk of age, renal ET-1 mRNA was 3.2-fold greater in cystic mice than in controls and continued to increase with the progression of cyst formation to reach 10.4-fold more than controls at 3 wk. ET-3 mRNA levels did not differ between cystic and control mice. Renal ETA and ETB receptor mRNA increased gradually in cystic mice with the progression of their cysts, reaching 4.2- and 6.3-fold increases over controls, respectively, at 3 wk. Proliferating cell nuclear antigen mRNA expression was also examined, and proliferating cell nuclear antigen mRNA levels were found to be significantly increased in the kidneys of cystic mice compared with controls: 2. 1-fold at 1 wk, 4.5-fold at 2 wk, and 7.8-fold at 3 wk. The mRNA levels for transforming growth factor beta (TGF-beta) and tumor necrosis factor alpha (TNF-alpha) in the kidneys of cystic mice were also examined and were found to be increased progressively with age (TGF-beta, 2.1-fold at 1 wk, 4.2-fold at 2 wk, and 6.2-fold at 3 wk; TNF-alpha, 2.2-fold at 1 wk, 3.8-fold at 2 wk, and 5.4-fold at 3 wk).(ABSTRACT TRUNCATED AT 250 WORDS)

Epidermal growth factor receptor mRNA expression in circulating tumor cells as a potential mechanism of molecular escape from regorafenib therapy.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 11517-11517
Author(s):  
Satoshi Matsusaka ◽  
Yan Ning ◽  
Dongyun Yang ◽  
Wu Zhang ◽  
Diana L. Hanna ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Mrna Expression ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Growth Factor Receptor ◽  
Potential Mechanism ◽  
Receptor Mrna ◽  
Epidermal Growth

159 Effect of bisphenol A and bisphenol S on AMH and AMHR mRNA expression during in vitro bovine oocyte maturation and early embryo development

2019 ◽  
Vol 31 (1) ◽  
pp. 204 ◽  
Author(s):  
A. Saleh ◽  
L. Favetta
Keyword(s):  
Bisphenol A ◽  
Mrna Expression ◽  
Cumulus Cells ◽  
Early Embryo ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Bisphenol S ◽  
Tissue Samples ◽  
Receptor Mrna

Exposure to chemicals with known endocrine-disrupting effects, such as bisphenol A (BPA) and bisphenol S (BPS), leads to repercussions on oocyte development and, ultimately, on fertility. Bisphenol A is a plasticizer used worldwide that has been detected in blood, urine, tissue samples and follicular fluid. Due to its widely reported detrimental effects, BPA has been substituted with its analogue BPS. Previous experiments in our laboratory have shown that exposure of bovine oocytes to physiologically relevant doses of BPA resulted in spindle abnormalities, reduced meiosis progression, decreased blastocyst rate and gene expression changes. However, the effects of BPS have not yet been investigated. Anti-Müllerian hormone (AMH) has been reported to be a good marker of ovarian reserve and oocyte developmental capability and is commonly used in assisted reproduction for diagnostic measurements. There is evidence that women undergoing IVF with higher BPA levels have lower AMH levels and pregnancy success. The aim of this study was to assess the effect of BPA and BPS on AMH and its receptor as measures of oocyte developmental capability. Abattoir-derived bovine cumulus-oocyte complexes (COC) were matured in vitro in 4 groups: (1) control, (2) vehicle (0.1% ethanol), (3) BPA (0.05mg mL−1 in 0.1% ethanol), and (4) BPS (0.05mg mL−1 in 0.1% ethanol). Pools of 30 COC, 30 denuded oocytes, and cumulus cells corresponding to denuded oocytes were collected for each of the 4 experimental groups, and a minimum of 4 biological replicates were used for each analysis. Anti-Müllerian hormone and AMH receptor mRNA expression was measured in COC, denuded oocytes, and their corresponding cumulus cells using quantitative real-time PCR. Statistical analyses were performed using 1-way ANOVA. Results showed a decrease (P<0.05) in AMH mRNA expression in BPA-treated oocytes (without cumulus cells). In addition, there was an increase (P<0.05) in mRNA AMH receptor levels in COC when treated with BPS. Finally, analyses on cumulus cells alone showed an increase (P<0.05) in the AMH receptor mRNA levels in BPA-treated cells. These results suggest that BPA has an effect on AMH mRNA transcript levels in oocytes, while affecting the receptor expression in cumulus cells. Conversely, BPS affects AMH indirectly, increasing the mRNA levels of its receptor only. Further investigation of the effects of BPA and BPS on AMH expression in in vitro-produced blastocysts derived from treated oocytes will aid in understanding the potential consequences of exposure to BPA and its analogues on early embryonic development.

scholarly journals Hyperlipidaemic effect of fish oil in Bio F1B hamsters

2004 ◽  
Vol 91 (3) ◽  
pp. 341-349 ◽  
Author(s):  
Pujitha P. de Silva ◽  
Phillip J. Davis ◽  
Sukhinder Kaur Cheema
Keyword(s):  
Fish Oil ◽  
Mrna Expression ◽  
Plasma Lipids ◽  
Control Diet ◽  
Dietary Cholesterol ◽  
Ldl Receptor ◽  
Safflower Seed ◽  
Mrna Levels ◽  
Receptor Mrna ◽  
Fish Oil Diet

We investigated the dietary influence of low and high levels of fish oil, supplemented with or without dietary cholesterol, on the plasma lipoprotein profile in Bio F1B hamsters, a model susceptible to diet-induced hyperlipidaemia. The MIX diet, a diet supplemented with a mixture of lard and safflower-seed oil, was used as the control diet to maintain the saturated MUFA and PUFA levels similar to the fish-oil diet. The animals were fed the specific diets for 2 weeks and fasted for 14h before killing. The plasma from the animals fed high levels of fish oil was milky and rich in chylomicron-like particles. The plasma total cholesterol, VLDL- and LDL-cholesterol and -triacylglycerol concentrations were significantly higher, whereas HDL-cholesterol was lower in hamsters fed fish oil compared with the MIX-diet-fed hamsters. Increasing the amount of fat in the diet increased plasma lipids in both the fish-oil- and the MIX-diet-fed hamsters; however, this hyperlipidaemic effect of dietary fat level was greater in the hamsters fed the fish-oil diet. The hepatic lipid concentrations were not dramatically different between the fish-oil-fed and the MIX-diet-fed hamsters. However, the hepatic LDL-receptor mRNA levels were significantly low in the fish-oil-fed hamsters compared with the MIX-diet-fed hamsters. Increasing the amount of fish oil in the diet further decreased the hepatic LDL-receptor mRNA expression. It is concluded that F1B hamsters are susceptible to fish-oil-induced hyperlipidaemia, especially at high fat levels, and this increase is partially explained by the inhibition of hepatic LDL-receptor mRNA expression.

Prenatal nicotine affects catecholamine gene expression in newborn rat carotid body and petrosal ganglion

2001 ◽  
Vol 91 (5) ◽  
pp. 2157-2165 ◽  
Author(s):  
Estelle B. Gauda ◽  
Reed Cooper ◽  
Patrice K. Akins ◽  
Guimei Wu
Keyword(s):  
Mrna Expression ◽  
Carotid Body ◽  
Ganglion Cells ◽  
Nicotine Exposure ◽  
Mrna Levels ◽  
Cardiorespiratory Control ◽  
Receptor Mrna ◽  
Prenatal Nicotine ◽  
Peripheral Arterial ◽  
Th Mrna

Nicotine exposure modifies the expression of catecholamine and opioid neurotransmitter systems involved in attenuation of hypoxic chemosensitivity. We used in situ hybridization histochemistry to determine the effect of prenatal and early postnatal nicotine exposure on tyrosine hydroxylase (TH), dopamine β-hydroxylase (DβH), preproenkephalin (PPE), and D2-dopamine receptor mRNA levels in the rat carotid body and petrosal ganglion during postnatal development. In the carotid body, nicotine increased TH mRNA expression in animals at 0 and 3 postnatal days (both, P < 0.05 vs. control) without affecting TH mRNA levels at 6 and 15 days. At 15 postnatal days, DβH mRNA levels were increased in the carotid body of nicotine-exposed animals. Dopamine D2-receptor mRNA levels in the carotid body increased with postnatal age but were unaffected by nicotine exposure. PPE was not expressed in the carotid body at any of the ages studied in control or treated animals. In the petrosal ganglion, nicotine increased the number of ganglion cells expressing TH mRNA in animals at 3 days ( P < 0.01 vs. control). DβH mRNA expression was not induced nor was PPE mRNA expression increased in the petrosal ganglion in treated animals. Prenatal nicotine exposure upregulates mRNAs involved in the synthesis of two inhibitory neuromodulators, dopamine and norepinephrine, in peripheral arterial chemoreceptors, which may contribute to abnormalities in cardiorespiratory control observed in nicotine exposed animals.

Starvation-induced increase in the parathyroid hormone/PTH-related protein receptor mRNA of bone and kidney in sham-operated and thyroparathyroidectomized rats

1997 ◽  
pp. 273-280 ◽  
Author(s):  
T Kawane ◽  
S Saikatsu ◽  
N Akeno ◽  
M Abe ◽  
N Horiuchi
Keyword(s):  
Parathyroid Hormone ◽  
Mrna Expression ◽  
Food Deprivation ◽  
Ion Homeostasis ◽  
Control Level ◽  
Mrna Levels ◽  
Related Protein ◽  
Receptor Mrna ◽  
Serum Pth ◽  
Pthrp Receptor

Parathyroid hormone (PTH) acts on bone and kidneys by binding to PTH/PTH-related protein (PTHrP) receptors and regulating calcium (Ca) and phosphorus (P) homeostasis. PTH/PTHrP receptor mRNA was expressed at high levels in PTH target tissues such as the kidneys and bone including the calvaria, femur, and tibia. Because short-term starvation influences Ca and P ion homeostasis, we measured changes in PTH/PTHrP receptor mRNA expression in the bone and kidneys. Food deprivation for 3 days decreased the serum Ca and P concentrations, and reinstitution of feeding for 2 days normalized the serum Ca level and significantly increased the serum P level. Concomitantly, rat immunoreactive PTH (riPTH) was increased during starvation and returned to the control level after 2 days of subsequent feeding. Serum 1 alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3) concentrations did not significantly change during starvation and subsequent feeding. Starvation up-regulated PTH/PTHrP receptor mRNA expression in both bone and kidney. The effects of food deprivation on the receptor transcript abundance were greater in bone (threefold increase compared with control) than in the kidney (1.8-fold increase), whereas the mRNA level increase by food deprivation was more rapid in the kidneys than in bone. The PTH-induced adenylyl cyclase activity of renal membranes increased in starvation. Feeding after starvation normalized the mRNA levels in both tissues. Serum PTH depression, initiated by thyroparathyroidectomy, did not affect PTH/PTHrP receptor mRNA levels in bone and kidney in rats that were fed or starved for 3 days. The abundance of receptor mRNA in bone and kidney was significantly lower in fed rats given either corticosterone or vehicle than in starved rats. These data indicate that starvation induces PTH/PTHrP receptor mRNA expression in bone and kidney, independently of serum PTH and corticosterone concentrations. The factors leading to up-regulated receptor mRNA induced by starvation remain unknown.

Substance P (NK1)- and neurokinin A (NK2)-receptor gene expression in inflammatory airway diseases

1995 ◽  
Vol 269 (3) ◽  
pp. L309-L317 ◽  
Author(s):  
T. R. Bai ◽  
D. Zhou ◽  
T. Weir ◽  
B. Walker ◽  
R. Hegele ◽  
...  
Keyword(s):  
Substance P ◽  
Mrna Expression ◽  
Airflow Obstruction ◽  
Ribonuclease Protection Assay ◽  
Neurokinin A ◽  
Mrna Levels ◽  
Nk1 Receptor ◽  
Receptor Mrna ◽  
Nk3 Receptor ◽  
Nk2 Receptor

The tachykinin neuropeptides substance P and neurokinin (NK) A have been postulated to participate in the inflammatory reaction in airways of smokers and asthmatics. We have examined the hypothesis that the expression of one or more of the three cloned tachykinin receptors (NK1, NK2, and NK3) is increased in inflammatory airway disorders, which could result in augmentation of the effect of released tachykinin neuropeptides. NK1 receptor and NK2 receptor but not NK3-receptor mRNA were detected by ribonuclease protection assay in RNA from both cartilaginous and membranous bronchi and subpleural lung. In lung samples containing membranous airways, NK2-receptor mRNA expression was increased fourfold in asthmatics compared with nonsmoking controls, whereas NK1-receptor mRNA levels were similar in the two groups. NK1- and NK2-receptor mRNA expression was increased twofold in smokers without airflow obstruction compared with nonsmokers, whereas NK1-receptor mRNA expression was significantly lower in patients with chronic obstructive pulmonary disease compared with smoking controls. In situ hybridization indicated NK1-receptor mRNA was expressed in submucosal glands and airway epithelial cells, whereas NK2-receptor and NK3-receptor mRNA were not detected. These observations have implications for the pathophysiology and treatment of both asthma and tobacco smoke-induced airway inflammation.

Developmental changes in endothelin expression and activity in the ovine fetal lung

2000 ◽  
Vol 278 (4) ◽  
pp. L785-L793 ◽  
Author(s):  
D. Dunbar Ivy ◽  
Timothy D. le Cras ◽  
Thomas A. Parker ◽  
Jeanne P. Zenge ◽  
Malathi Jakkula ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Vascular Tone ◽  
Receptor Gene ◽  
Receptor Activity ◽  
Mrna Levels ◽  
Developmentally Regulated ◽  
Receptor Mrna ◽  
Fetal Lamb ◽  
Receptor Gene Expression

Mechanisms that regulate endothelin (ET) in the perinatal lung are complex and poorly understood, especially with regard to the role of ET before and after birth. We hypothesized that the ET system is developmentally regulated and that the balance of ETAand ETB receptor activity favors vasoconstriction. To test this hypothesis, we performed a series of molecular and physiological studies in the fetal lamb, newborn lamb, and adult sheep. Lung preproET-1 mRNA levels, tissue ET peptide levels, and cellular localization of ET-1 expression were determined by Northern blot analysis, peptide assay, and immunohistochemistry in distal lung tissue from fetal lambs between 70 and 140 days (term = 145 days), newborn lambs, and ewes. Lung mRNA expression for the ETA and ETB receptors was also measured at these ages. We found that preproET-1 mRNA expression increased from 113 to 130 days gestation. Whole lung ET protein content was highest at 130 days gestation but decreased before birth in the fetal lamb lung. Immunolocalization of ET-1 protein showed expression of ET-1 in the vasculature and bronchial epithelium at all gestational ages. ETA receptor mRNA expression and ETB receptor mRNA increased from 90 to 125 and 135 days gestation. To determine changes in activity of the ETA and ETBreceptors, we studied the effect of selective antagonists to the ETA or ETB receptors at 120, 130, and 140 days of fetal gestation. ETA receptor-mediated vasoconstriction increased from 120 to 140 days, whereas blockade of the ETBreceptor did not change basal fetal pulmonary vascular tone at any age examined. We conclude that the ET system is developmentally regulated and that the increase in ETA receptor gene expression correlates with the onset of the vasodilator response to ETA receptor blockade. Although ETB receptor gene expression increases during late gestation, the balance of ET receptor activity favors vasoconstriction under basal conditions. We speculate that changes in ET receptor activity play important roles in regulation of pulmonary vascular tone in the ovine fetus.

Kinin B1 and B2 receptor mRNA expression in the hypothalamus of spontaneously hypertensive rats

2002 ◽  
Vol 80 (4) ◽  
pp. 258-263 ◽  
Author(s):  
F Qadri ◽  
W Häuser ◽  
O Jöhren ◽  
P Dominiak
Keyword(s):  
Mrna Expression ◽  
Spontaneously Hypertensive Rats ◽  
Mrna Levels ◽  
Hypertensive Rats ◽  
Kinin System ◽  
Spontaneously Hypertensive ◽  
Receptor Mrna ◽  
Wky Rats ◽  
Wistar Kyoto ◽  
Kallikrein Kinin System

The central hypertensive effects induced by bradykinin are known to be mediated via B2 receptors, which are present constitutively in the brain. B1 receptors are rapidly upregulated during inflammation, hyperalgesia, and experimental diabetes. The hypothalamus plays an important role in the regulation of cardiovascular homeostasis, and all components of kallikrein–kinin system have been identified in this area. Therefore, we analyzed the mRNA expression of B1 and B2 receptors in the hypothalamus of spontaneously hypertensive rats (SHR) by RT-PCR. Male SHR were studied at three different ages corresponding to the three phases in the development of hypertension: (i) 3–4 (prehypertensive), (ii) 7–8 (onset of hypertension), and (iii) 12–13 weeks (established hypertension) after birth, and compared with age-matched Wistar–Kyoto (WKY) rats. At all ages tested, B2 receptor mRNA levels in the hypothalamus of SHR were higher than age-matched WKY rats (p < 0.001). However, the B1 receptor mRNA levels were higher at the established phase of hypertension only. We conclude that B1 and B2 receptor mRNA are differentially expressed in the hypothalamus of SHR and may play different roles in the pathogenesis of hypertension: upregulation of B2 receptor mRNA from early age may participate in the pathogenesis of hypertension, whereas an upregulation of B1 receptor mRNA in the established phase of hypertension may reflect an epiphenomenon in essential hypertension.Key words: kinin receptors, mRNA expression, hypothalamus, SHR, WKY.

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