scholarly journals Telomere Dynamics Throughout Spermatogenesis

Genes ◽  
2019 ◽  
Vol 10 (7) ◽  
pp. 525 ◽  
Author(s):  
Heather Fice ◽  
Bernard Robaire
Keyword(s):  
Brown Norway ◽  
Cell Replication ◽  
Sprague Dawley ◽  
Telomere Shortening ◽  
Toxicant Exposure ◽  
Relative Telomere Length ◽  
Sd Rats ◽  
Epididymal Maturation ◽  
Age Dependent ◽  
Pachytene Spermatocytes

Telomeres are repeat regions of DNA that cap either end of each chromosome, thereby providing stability and protection from the degradation of gene-rich regions. Each cell replication causes the loss of telomeric repeats due to incomplete DNA replication, though it is well-established that progressive telomere shortening is evaded in male germ cells by the maintenance of active telomerase. However, germ cell telomeres are still susceptible to disruption or insult by oxidative stress, toxicant exposure, and aging. Our aim was to examine the relative telomere length (rTL) in an outbred Sprague Dawley (SD) and an inbred Brown Norway (BN) rat model for paternal aging. No significant differences were found when comparing pachytene spermatocytes (PS), round spermatids (RS), and sperm obtained from the caput and cauda of the epididymis of young and aged SD rats; this is likely due to the high variance observed among individuals. A significant age-dependent decrease in rTL was observed from 115.6 (±6.5) to 93.3 (±6.3) in caput sperm and from 142.4 (±14.6) to 105.3 (±2.5) in cauda sperm from BN rats. Additionally, an increase in rTL during epididymal maturation was observed in both strains, most strikingly from 115.6 (±6.5) to 142 (±14.6) in young BN rats. These results confirm the decrease in rTL in rodents, but only when an inbred strain is used, and represent the first demonstration that rTL changes as sperm transit through the epididymis.

Abstract P189: AT 1 R-Dependent Blood-Brain Barrier Disruption Precedes Neuroinflammation In Age-Dependent Hypertension

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Kayla M Nist ◽  
Jesse Moreira ◽  
Richard D Wainford
Keyword(s):  
Blood Pressure ◽  
Blood Brain Barrier ◽  
Neural Control ◽  
Brain Barrier ◽  
Sprague Dawley ◽  
Control Center ◽  
Blood Brain Barrier Disruption ◽  
Sd Rats ◽  
Blood Brain ◽  
Age Dependent

AIM: We hypothesized paraventricular nucleus (PVN)-specific blood-brain barrier (BBB) dysfunction and neuroinflammation contribute to hypertension and sympathoexcitation that can be attenuated by an Angiotensin II Type 1 Receptor (AT 1 R)-dependent mechanism in the aging Sprague-Dawley (SD) rat. Methods: Naïve male SD rats aged 3-, 8- and 16-months-old (MO) (N=4-6/gp) were used in the following studies. Separate groups of 16 MO rats were administered losartan (21 days; s.c. 3 mg/kg/day) or hydrochlorothiazide (14 days; s.c. 4 mg/kg/day). Blood pressure (femoral cannulation) and plasma NE (ELISA) were assessed at end of study. In separate groups, BBB dysfunction was assessed via PVN FITC extravasation using intravascular co-infusion of FITC-Dextran (10 kDa) and rhodamine B isothiocyanate-Dextran (70 kDa). IHC/IF was performed in naive and losartan-treated rats for microglia (CD11b/c) and astrocytes (GFAP) in the PVN and subfornical organ (SFO). Results: Male SD rats develop HTN and sympathoexcitation with age. At 8 and 16 MO, rats exhibit PVN BBB dysfunction (increased FITC extravasation). However, only 16 MO rats exhibit significant PVN neuroinflammation (increased microglial activation and astrocyte reactivity). In the SFO, there is no evidence of age-dependent neuroinflammation. Losartan and HCTZ both significantly lower blood pressure to similar levels, however, only losartan significantly attenuates PVN BBB dysfunction and neuroinflammation. Conclusions: Within the PVN, a known neural control center, there are AT 1 R-dependent increases in PVN BBB disruption and neuroinflammation that we speculate contribute to hypertension in aging SD rats.

scholarly journals Postnatal developmental changes in CO2 sensitivity in rats

2006 ◽  
Vol 101 (4) ◽  
pp. 1097-1103 ◽  
Author(s):  
S. E. Davis ◽  
G. Solhied ◽  
M. Castillo ◽  
M. Dwinell ◽  
D. Brozoski ◽  
...  
Keyword(s):  
Pulmonary Ventilation ◽  
Strain Differences ◽  
Developmental Changes ◽  
Brown Norway ◽  
Sprague Dawley ◽  
Dependent Plasticity ◽  
Co2 Sensitivity ◽  
Age Dependent ◽  
High Degree ◽  
Physiological Systems

Ventilatory sensitivity to CO2 in awake adult Brown Norway (BN) rats is 50–75% lower than in adult Sprague-Dawley (SD) and salt-sensitive Dahl S (SS) rats. The purpose of the present study was to test the hypothesis that this difference would be apparent during the development of CO2 sensitivity. Four litters of each strain were divided into four groups such that rats were exposed to 7% inspired CO2 for 5 min in a plethysmograph every third day from postnatal day (P) 0 to P21 and again on P29 and P30. From P0 to P14, CO2 exposure increased pulmonary ventilation (V̇e) by 25–50% in the BN and SD strains and between 25 to over 200% in the SS strain. In all strains beginning around P15, the response to CO2 increased progressively reaching a peak at P19–21 when V̇e during hypercapnia was 175–225% above eucapnia. There were minimal changes in CO2 sensitivity between P21 and P30, and at both ages there were minimal between-strain differences. At P30, the response to CO2 in the SS and SD strains was near the adult response, but the response in the BN rats was 100% greater at P30 than in adults. We conclude that 1) CO2-sensing mechanisms, and/or mechanisms downstream from the chemoreceptors, change dramatically at the age in rats when other physiological systems are also maturing (∼P15), and 2) there is a high degree of age-dependent plasticity in CO2 sensitivity in rats, which differs between strains.

scholarly journals Age-Dependent Accumulation of 8-Oxoguanine in the DNA and RNA in Various Rat Tissues

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Ben Nie ◽  
Wei Gan ◽  
Fei Shi ◽  
Guo-Xin Hu ◽  
Lian-Guo Chen ◽  
...  
Keyword(s):  
Nucleic Acids ◽  
Rna Degradation ◽  
Rat Tissues ◽  
Sprague Dawley ◽  
Dna And Rna ◽  
Sd Rats ◽  
Age Dependent ◽  
Tissue Specimens ◽  
The Relationship ◽  
The Brain

The relationship between the oxidative damage of nucleic acids and aging of animals was investigated by analyzing the nucleic acids derived from various tissue specimens of naturally aged Sprague-Dawley (SD) rats. For this purpose, we established an accurate and sensitive isotope-diluted LC-MS/MS method to determine the levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dGsn) in DNA and 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn) in RNA. An age-dependent increase in oxidative DNA and RNA damage was observed in the various organs examined, including the brain, liver, kidneys, and testes. Similar increases in the 8-oxo-dGsn and 8-oxo-Gsn contents were observed in three parts of the brain, the hippocampus, cerebral cortex, and cerebellum, among which, the values for the hippocampus were always the highest. When the oxidized guanosine metabolites were quantified with urine, a similar age-dependent increase was observed for both 8-oxo-dGsn and 8-oxo-Gsn. However, unlike the results of nucleic acid samples derived from the tissues, the amount of 8-oxo-Gsn was significantly higher compared to that of 8-oxo-dGsn, probably reflecting the fact that RNA degradation occurs more frequently than DNA degradation. Our finding indicates that the amount of urinary 8-oxo-Gsn could be considered as a biomarker for the sensitive measurement of oxidative stress and aging.

scholarly journals Elevation of fumarase attenuates hypertension and can result from a nonsynonymous sequence variation or increased expression depending on rat strain

2017 ◽  
Vol 49 (9) ◽  
pp. 496-504 ◽  
Author(s):  
Kristie Usa ◽  
Yong Liu ◽  
Aron M. Geurts ◽  
Yuan Cheng ◽  
Jozef Lazar ◽  
...  
Keyword(s):  
Sequence Variation ◽  
Specific Activity ◽  
Tricarboxylic Acid Cycle ◽  
Renal Medulla ◽  
Brown Norway ◽  
Sprague Dawley ◽  
Rat Strains ◽  
High Salt Diet ◽  
Sd Rats ◽  
Rat Strain

The activity of fumarase, an enzyme in the tricarboxylic acid cycle, is lower in Dahl salt-sensitive SS rats compared with SS.13BN rats. SS.13BN rats have a Brown Norway (BN) allele of fumarase and exhibit attenuated hypertension. The SS allele of fumarase differs from the BN allele by a K481E sequence variation. It remains unknown whether higher fumarase activities can attenuate hypertension and whether the mechanism is relevant without the K481E variation. We developed SS-TgFh1 transgenic rats overexpressing fumarase on the background of the SS rat. Hypertension was attenuated in SS-TgFh1 rats. Mean arterial pressure in SS-TgFh1 rats was 20 mmHg lower than transgene-negative SS littermates after 12 days on a 4% NaCl diet. Fumarase overexpression decreased H2O2, while fumarase knockdown increased H2O2. Ectopically expressed BN form of fumarase had higher specific activity than the SS form. However, sequencing of more than a dozen rat strains indicated most rat strains including salt-insensitive Sprague-Dawley (SD) rats had the SS allele of fumarase. Despite that, total fumarase enzyme activity in the renal medulla was still higher in SD rats than in SS rats, which was associated with higher expression of fumarase in SD. H2O2 can suppress the expression of fumarase. Renal medullary interstitial administration of fumarase siRNA in SD rats resulted in higher blood pressure on the high-salt diet. These findings indicate elevation of total fumarase activity attenuates the development of hypertension and can result from a nonsynonymous sequence variation in some rat strains and higher expression in other rat strains.

scholarly journals The long-term bio-behavioural effects of juvenile sildenafil treatment in Sprague-Dawley versus Flinders Sensitive Line rats

2021 ◽  
pp. 1-20
Author(s):  
Juandré Lambertus Bernardus Saayman ◽  
Stephanus Frederik Steyn ◽  
Christiaan Beyers Brink
Keyword(s):  
Sprague Dawley ◽  
Long Term Effects ◽  
Bdnf Level ◽  
Treatment Groups ◽  
Sd Rats ◽  
Behavioural Effects ◽  
Sensitive Line ◽  
Level Analysis ◽  
Flinders Sensitive Line

Abstract Objective: To investigate the long-term effects of juvenile sub-chronic sildenafil (SIL) treatment on the depressive-like behaviour and hippocampal brain-derived neurotrophic factor (BDNF) levels of adult Sprague-Dawley (SD) versus Flinders Sensitive Line (FSL) rats. Methods: SD and FSL rats were divided into pre-pubertal and pubertal groups, whereafter 14-day saline or SIL treatment was initiated. Pre-pubertal and pubertal rats were treated from postnatal day 21 (PND21) and PND35, respectively. The open field and forced swim tests (FST) were performed on PND60, followed by hippocampal BDNF level analysis one day later. Results: FSL rats displayed greater immobility in the FST compared to SD rats (p < 0.0001), which was reduced by SIL (p < 0.0001), regardless of treatment period. Hippocampal BDNF levels were unaltered by SIL in all treatment groups (p > 0.05). Conclusion: Juvenile sub-chronic SIL treatment reduces the risk of depressive-like behaviour manifesting during young adulthood in genetically susceptible rats.

Toxicokinetic and Genotoxicity Study of NNK in Male Sprague-Dawley Rats Following Nose-Only Inhalation Exposure, Intraperitoneal Injection, and Oral Gavage

2021 ◽  
Author(s):  
Shu-Chieh Hu ◽  
Matthew S Bryant ◽  
Estatira Sepehr ◽  
Hyun-Ki Kang ◽  
Raul Trbojevich ◽  
...  
Keyword(s):  
Human Lung ◽  
Inhalation Exposure ◽  
Systemic Exposure ◽  
Sprague Dawley ◽  
Oral Gavage ◽  
Sd Rats ◽  
New Information ◽  
Sprague Dawley Rats ◽  
Tissue Specimens

Abstract The tobacco-specific nitrosamine NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] is found in tobacco products and tobacco smoke. NNK is a potent genotoxin and human lung carcinogen; however, there are limited inhalation data for the toxicokinetics (TK) and genotoxicity of NNK in vivo. In the present study, a single dose of 5x10−5, 5x10−3, 0.1, or 50 mg/kg body weight (BW) of NNK, 75% propylene glycol (vehicle control), or air (sham control) was administered to male Sprague-Dawley (SD) rats (9-10 weeks age) via nose-only inhalation (INH) exposure for 1 hour. For comparison, the same doses of NNK were administered to male SD rats via intraperitoneal (IP) injection and oral gavage (PO). Plasma, urine, and tissue specimens were collected at designated timepoints and analyzed for levels of NNK and its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and tissue levels of DNA adduct O6-methylguanine by LC/MS/MS. TK data analysis was performed using a non-linear regression program. For the genotoxicity subgroup, tissues were collected at 3 hours post-dosing for comet assay analysis. Overall, the TK data indicated that NNK was rapidly absorbed and metabolized extensively to NNAL after NNK administration via the three routes. The IP route had the greatest systemic exposure to NNK. NNK metabolism to NNAL appeared to be more efficient via INH than IP or PO. NNK induced significant increases in DNA damage in multiple tissues via the three routes. The results of this study provide new information and understanding of the toxicokinetics and genotoxicity of NNK.

Abstract P242: The Role Of Kappa Opioid Receptors In The Development Of Hypertension And Kidney Injury In Sprague-Dawley Rats

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Daria Golosova ◽  
Adrian Zietara ◽  
Ruslan Bohovyk ◽  
Vladislav Levchenko ◽  
Alexander Staruschenko
Keyword(s):  
Blood Pressure ◽  
Sprague Dawley ◽  
Glomerular Injury ◽  
Kappa Opioid ◽  
Injury Score ◽  
Calcium Response ◽  
Blood Pressure Elevation ◽  
Isolated Glomeruli ◽  
Pressure Elevation ◽  
Sd Rats

The extensive use of opioid-based pain management strongly correlates with poor cardiovascular and cardiorenal outcomes. Our recent studies suggest that treatment with kappa opioid receptor (KOR) agonist BRL 52537 leads to the progression of chronic kidney disease (CKD) and aggravation of salt-sensitive hypertension. We hypothesize that stimulation of KORs leads to blood pressure elevation, albuminuria, and kidney damage in healthy Sprague-Dawley (SD) rats. To characterize the effect of the KOR agonist BRL 52537 on the development of blood pressure and kidney function in vivo , SD rats were treated with a daily i.v. bolus infusion of BRL 52537 or a corresponding vehicle. To test the contribution of KOR stimulation on calcium homeostasis in podocytes, BRL 52537 was used on freshly isolated glomeruli from SD rats. Single-channel analysis was applied to assess the effect of KORs stimulation on TRPC6 channel activity in the human immortalized podocytes. Chronic treatment with BRL 52537 leads to increased mean arterial pressure (88±1 vs 101±4 mmHg, vehicle vs treated, p<0.05), podocyte basal calcium (90±12 vs 216±16 a.u., vehicle vs treated, p<0.05), and GFB impairment in SD rats which is reflected by a transient increase in albumin excretion (Alb/cre ratio 0.35±0.1 vs 0.72±0.2, vehicle vs treated, p<0.05). Cumulative probability distribution analysis of the glomerular injury score revealed a rightward shift toward a high glomerular injury score in the group treated with BRL 52537 (p<0.05). Angiotensin II level was higher in a BRL-treated group (156±17 vs 232±59 pmol, vehicle vs treated, p=0.065); however, it did not reach a statistical difference. Acute application of BRL 52537 resulted in sustained calcium response (0.23±0.01 a.u., Fluo4/FuraRed, maximum calcium response) in freshly isolated glomeruli from SD rats. Furthermore, patch-clamp experiments in human immortalized podocytes (cell-attached configuration) revealed that BRL 52537 activated TRPC6 channels. Taken together, these data support the hypothesis that administration of opioids in SD rats leads to activation of the KOR/TRPC6 pathway, which in turn led to glomerular filtration barrier impairment, increased glomerular damage, and blood pressure elevation.

Abstract 131: Anti-inflammatory and Mitochondrial Effects of Butyrate in Shr Astrocytes in vitro

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Tao Yang ◽  
Ty Redler ◽  
Carla G Bueno Silva ◽  
Rebeca Arocha ◽  
Jordan Schmidt ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Mitochondrial Respiration ◽  
Rna Isolation ◽  
Inflammatory Factors ◽  
Pcr Analysis ◽  
Sprague Dawley ◽  
Beneficial Effects ◽  
Sd Rats ◽  
Anti Inflammatory

Emerging evidence demonstrates a significant link between gut dysbiosis and hypertension (HTN). Butyrate is one of the major fermented end-products of gut microbiota that reportedly produces beneficial effects on the immune system and metabolism. A contraction in butyrate-producing bacteria in the gut of spontaneously hypertensive rats (SHR) suggests that reduced butyrate may be associated with HTN. Considering its role in mitochondrial metabolism, we proposed that the positive anti-inflammatory effects of butyrate may be mediated via improvement in mitochondrial function in astrocytes. Methods: Sprague Dawley (SD) and SHR primary astrocytes from two-day old pups were cultured in DMEM, supplemented with 10% FBS and 1% pen/strep, for 14 days, prior to treatment with butyrate (0-1mM) for 4 hours. Cells were then subjected to the Seahorse XFe24 Extracellular Flux Analyzer to evaluate mitochondrial function following butyrate treatment. Additional samples were collected for total RNA isolation for real time PCR analysis of inflammatory factors and transcripts related to mitochondrial function and stress. Results: Butyrate significantly increased both basal and maximal mitochondrial respiration (by 3-4 fold, P<0.001) and elevated proton leak (by 4 fold, P<0.01) in astrocytes from SD rats but not SHR. Furthermore, we observed a trend for an increase in both ATP-linked and non-mitochondrial respiration in SD astrocytes compared to SHR (by 2-3 fold, P=0.07). This was associated with a significant reduction in relative expression levels in catalase (by 50%, P<0.05) and a trend in reduction in Sod1 and Sod2 (by 25%-50%, P=0.1) in astrocytes harvested from SD rats but not the SHR. Conversely, butyrate significantly lowered expression of pro-inflammatory Ccl2 (by 33%, P<0.05) and Tlr4 (by 48%, P <0.05) in astrocytes of SHR, but not SD rats. Conclusion: Butyrate modulated mitochondrial bioenergetics in SD but not the SHR, suggesting that the mitochondria of astrocytes may be less sensitive to the effects of butyrate in HTN. In addition, butyrate reduced inflammatory mediators in the SHR, but had no effect in the SD rat astrocytes. Thus, central anti-inflammatory effects of butyrate may be mediated via a mitochondria-independent mechanism.

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