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

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.

2003 ◽  
Vol 124 (4) ◽  
pp. A677
Author(s):  
Hillevi Mattsson ◽  
Zahra Arani ◽  
Alfred Bayati ◽  
Claes Ekman ◽  
David H. Overstreet ◽  
...  

2015 ◽  
Vol 27 (6) ◽  
pp. 345-352 ◽  
Author(s):  
Thea Pinholt Lillethorup ◽  
Peter Iversen ◽  
Gregers Wegener ◽  
Doris Jeanne Marie Doudet ◽  
Anne Marlene Landau

ObjectivesDisturbances in the noradrenergic system, including alterations in the densities of α2-adrenoceptors, are posited to be involved in the pathophysiology of depression. In this study, we investigate the binding of α2-adrenoceptors in regions relevant to depression in an animal model of depression.MethodsUsing in vitro autoradiography techniques and the selective α2-ligand, [3H]RX 821002, we investigated the density of α2-adrenoceptors in female Flinders-sensitive line (FSL) rats, a validated model of depression, and in two traditional control groups – female Flinders-resistant line (FRL) and Sprague-Dawley (SD) rats.ResultsThe α2-adrenoceptor density was increased in most regions of the FSL rat brain when compared with SD rats (10% across regions). Moreover, the α2-adrenoceptor density was further increased in the FRL rats compared with both FSL (10% across regions) and SD rats (24% across regions).ConclusionsThe increase in α2-adrenoceptor binding in cortical regions in the FSL strain compared with the SD control strain is in accord with α2-adrenoceptor post-mortem binding data in suicide victims with untreated major depression. However, the differences in binding observed in the two control groups were unexpected and suggest the need for further studies in a larger cohort of animals of both sexes.


Author(s):  
Ting Xu ◽  
Meng Zhao ◽  
Huan Li ◽  
Xiuwen Zhou ◽  
Bailin Liu ◽  
...  

Objective: Antenatal exposure to glucocorticoids increases cardiovascular risks related to vascular dysfunctions in offspring, although underlying mechanisms are still unknown. As an important vascular mediator, high-conductance Ca 2+ -activated K + channels (BK) plays an essential role in determining vascular tone. Long-term effects of antenatal glucocorticoids on BK in offspring are largely unknown. This study examined the effects and mechanisms of antenatal exposure to clinically relevant doses of glucocorticoids on vascular BK in offspring. Approach and Results: Pregnant Sprague-Dawley rats received synthetic glucocorticoids dexamethasone or vehicle during the last week of pregnancy. Vascular functions, cellular electrophysiology, target gene expression, and promoter methylation were examined in mesenteric arteries of male offspring (gestational day 21 [fetus] and postnatal day 120 [adult offspring]). Antenatal dexamethasone exposure impaired BK activators-mediated relaxation and reduced whole-cell BK currents in mesenteric arteries. Antenatal dexamethasone exposure did not alter Ca 2+ /voltage-sensitivity of BK but downregulated the expressions of BK α and β1 subunits in both fetal and adult mesenteric arteries. In addition, increased promoter methylations within BKα and BKβ1 were compatible with reduced expressions of the 2 genes. Conclusions: Our findings showed a profound and long-term impact of antenatal dexamethasone exposure on vascular BK via an altered epigenetic pattern from fetal stage to adulthood, advancing understanding of prolonged adverse effects and mechanisms of antenatal glucocorticoids exposure on vascular health in offspring.


Fishes ◽  
2018 ◽  
Vol 3 (4) ◽  
pp. 38
Author(s):  
Joacim Näslund

This study investigated whether compensatory growth causes long-term effects in relative brain- or intestine size in a wild, predominantly anadromous, population of brown trout (Salmo trutta). The subject fish belonged to two treatment groups; one group had undergone starvation and subsequent growth compensation, while the other were unrestricted controls. The main hypothesis that compensatory growth would negatively affect brain and intestinal size, as a consequence of growth trade-offs during the compensatory phase, could not be supported as no significant differences were detected between the treatment groups. Further exploratory analyses suggested that males and females started to diverge in both brain and intestine size at around 130 mm fork length, with females developing relatively smaller brains and larger intestines. The size at which the differences appear is a typical size for smoltification (saltwater preadaptation), and females tend to smoltify to a higher proportion than males. Smoltification is known to cause a more elongated morphology and relatively smaller heads in salmonids, and the marine lifestyle is associated with rapid growth, which could require relatively larger intestines. Hence, these emerging sex differences could be a consequence of sex-biased smoltification rates. An investigation of wild smolts of both sexes indicated no differences in brain or intestine mass between male and female smolts.


2012 ◽  
Vol 3 (5) ◽  
pp. 350-357 ◽  
Author(s):  
C. F. Rueda-Clausen ◽  
J. S. Morton ◽  
G. Y. Oudit ◽  
Z. Kassiri ◽  
Y. Jiang ◽  
...  

We have previously shown that adult rat offspring born intrauterine growth restricted (IUGR) as a result of a prenatal hypoxic insult exhibit several cardiovascular characteristics that are compatible with common manifestations of chronic iron toxicity. As hypoxia is one of the major regulators of iron absorption and metabolism, we hypothesized that hypoxia-induced IUGR offspring will have long-term changes in their ability to regulate iron metabolism leading to myocardial iron deposition and induction of myocardial oxidative stress. Pregnant Sprague Dawley rats were randomized to control (n = 8) or maternal hypoxia (11.5% oxygen; n = 8) during the last 6 days of pregnancy. At birth, litters were reduced to eight pups (four male and four female). At 4 or 12 months of age, offspring were euthanatized and samples (blood and myocardium) were collected. In only the male offspring, IUGR and aging were associated with an increase in myocardial markers of oxidative stress such as oxidized/reduced glutathione ratio and malondialdehyde. Aged male IUGR offspring also exhibited interstitial myocardial remodeling characterized by myocyte loss and disrupted extracellular matrix.Contrary to our hypothesis, however, neither IUGR nor aging were associated with changes in any systemic or local markers of iron metabolism. Our results suggest that hypoxic insults leading to IUGR produce long-term effects on the levels of oxidative stress and connective tissue distribution in the myocardium of male but not female offspring.


PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. e57608 ◽  
Author(s):  
Liesbeth Knaepen ◽  
Ine Rayen ◽  
Thierry D. Charlier ◽  
Marianne Fillet ◽  
Virginie Houbart ◽  
...  

2004 ◽  
Vol 23 (4) ◽  
pp. 239-247 ◽  
Author(s):  
Darryl P. Arfsten ◽  
Eric W. Johnson ◽  
Angie R. Thitoff ◽  
Anne E. Jung ◽  
Erin R. Wilfong ◽  
...  

A number of studies have demonstrated a protective effect associated with N-acetyl-l-cysteine (NAC) against toxic chemical exposure. However, the impact of long-term oral dosing on tissue pathology has not been determined. In this study, the authors assessed the impact of long-term oral NAC administration on organ histopathology and tissue glutathione (GSH) and total glutathione- S-transferase (GST) activity levels in Sprague-Dawley (SD) rats. Groups of 20 SD rats (10 males, 10 females), 8 weeks of age, were dosed daily by oral gavage with deionized H2O (negative controls) or NAC solution at a rate of 600 or 1200 mg/kg/day for 30 days. Animals were euthanized 6 h after treatment on study day 30. There were no significant differences in final body weights or weekly average weight gain between treatment groups. Serum alanine amino-transferase (ALT) activities were significantly elevated ( p ≤.05) in NAC-treated animals compared to controls when measured on study day 30. Histopathologic evaluation of the stomach, small intestine, liver, kidneys, spleen, thymus, and lungs revealed no lesions associated with NAC administration. When measured on study day 30, total GST activity for kidney and skin from NAC-treated animals were increased 39% to 131% as compared to controls. Tissue GSH concentrations from NAC-treated animals were increased 24% to 81% as compared with negative controls. Further studies are needed to determine if the observed increase in tissue GSH concentration and GST activity provide a degree of chemoprotection against dermal and systemic chemical toxicants.


2005 ◽  
Vol 23 (3) ◽  
pp. 311-317 ◽  
Author(s):  
Sherry O. Kasper ◽  
Christy S. Carter ◽  
Carlos M. Ferrario ◽  
Detlev Ganten ◽  
Leon F. Ferder ◽  
...  

Transgenic rats with targeted decreased glial expression of angiotensinogen (ASrAogen rats) did not show an increase in systolic pressure compared with Sprague-Dawley (SD) rats during aging (15–69 wk of age). ASrAogen animals had lower body weights throughout the study, similar to reports for animals with systemic knockout of angiotensinogen or treated long term with renin-angiotensin system (RAS) blockers. Further characterization of indexes of growth and metabolism in ASrAogen rats compared with (mRen2)27 and SD rats, which express elevated versus normal brain and tissue angiotensin II levels, respectively, revealed that serum leptin was 100–200% higher in SD and (mRen2)27 rats at 46 wk and 69 wk of age. Consistent with low serum leptin, ASrAogen rats had higher food intake (73%) compared with SD or (mRen2)27 rats. (mRen2)27 rats had higher resting insulin levels than ASrAogen rats at all ages. Insulin levels were constant during aging in ASrAogen rats, whereas an increase occurred in SD rats, leading to higher insulin levels at 46 and 69 wk of age compared with ASrAogen rats. IGF-1 was comparable among strains at all ages, but (mRen2)27 rats had longer and ASrAogen rats had shorter tail lengths versus SD rats at 15 wk of age. In conclusion, reduced expression of glial angiotensinogen blunts the age-dependent rise in insulin levels and weight gain, findings that mimic the effects of long-term systemic blockade of the RAS or systemic knockout of angiotensinogen. These data implicate glial angiotensinogen in the regulation of body metabolism as well as hormonal mechanisms regulating blood pressure.


2012 ◽  
Vol 92 (4) ◽  
pp. 513-524 ◽  
Author(s):  
N. Quiniou ◽  
A. Quinsac ◽  
K. Crépon ◽  
J. Evrard ◽  
C. Peyronnet ◽  
...  

Quiniou, N., Quinsac, A., Crépon, K., Evrard, J., Peyronnet, C., Bourdillon, A., Royer, E. and Etienne, M. 2012. Effects of feeding 10% rapeseed meal (Brassica napus) during gestation and lactation over three reproductive cycles on the performance of hyperprolific sows and their litters. Can. J. Anim. Sci. 92: 513–524. Largely due to increased production of biodiesel, there is a greater availability of solvent-extracted rapeseed meal (RM) in France, making it competitive for feeding pigs. Nevertheless, the long-term effects of dietary glucosinolates (GSL) when feeding RM on sow reproductive and litter performance are a persistent concern to feed manufacturers. Four batches of 24 hyperprolific sows were fed to evaluate the effects of including 0 or 10% RM [14.5 µmol GLS g−1dry matter (DM) basis] in the gestation and lactation diets over three reproductive cycles. Intake of dietary GLS remained below 5 mmol d−1over the gestation period and averaged 8 mmol d−1over the lactation period, corresponding to less than 2 µmol GLS g−1DM basis. Lactation feed intake, sow body weight and backfat, and the length of the weaning-to-estrus interval were not different (P>0.05) between treatment groups. Sows fed diets with 10% or no RM farrowed 43.6 and 43.8 piglets over three reproductive cycles, respectively (P>0.05). Piglet weight at birth or weaning, survival and litter weight gain were not affected (P>0.05) by dietary RM inclusion. Similar (P>0.10) plasma thyroxin levels of sows and piglets indicated that thyroid function was not altered by RM inclusion. In conclusion, feeding gestation and lactation diets including 10% RM to hyper prolific sows over three parities was safe and did not affect sow longevity, reproductive or litter performance.


2001 ◽  
Vol 281 (2) ◽  
pp. R635-R644 ◽  
Author(s):  
Azeez A. Aileru ◽  
Aline De Albuquerque ◽  
John M. Hamlyn ◽  
Paolo Manunta ◽  
Jui R. Shah ◽  
...  

Altered sympathetic nervous system activity has been implicated often in hypertension. We examined short-term potentiation [posttetanic potentiation (PTP)] and long-term potentiation (LTP) in the isolated superior cervical ganglia (SCG) from Sprague-Dawley (SD) rats given vehicle, digoxin, or ouabain by subcutaneous implants as well as in animals with ouabain-induced hypertension (OHR), and inbred Baltimore ouabain-resistant (BOR) and Baltimore ouabain-sensitive (BOS) strains of rats. Postganglionic compound action potentials (CAP) were used to determine PTP and LTP following a tetanic stimulus (20 Hz, 20 s). Baseline CAP magnitude was greater in ganglia from OHR than in vehicle-treated SD rats before tetanus, but the decay time constant of PTP was significantly decreased in OHR and in rats infused with digoxin that were normotensive. In hypertensive BOS and OHR, the time constants for the decay of both PTP and LTP ( t L) were increased and correlated with blood pressure (slope = 0.15 min/mmHg, r = 0.52, P < 0.047 and 6.7 min/mmHg, r = 0.906, P < 0.0001, respectively). In BOS and OHR, t L (minutes) was 492 ± 40 ( n = 7) and 539 ± 41 ( n = 5), respectively, and differed ( P < 0.05) from BOR (257 ± 48, n = 4), SD vehicle rats (240 ± 18, n = 4), and captopril-treated OHR (370 ± 52, n = 5). After the tetanus, the CAP at 90 min in BOS and OHR SCG declined less rapidly vs. SD vehicle rats or BOR. Captopril normalized blood pressure and t L in OHR. We conclude that the duration of ganglionic LTP and blood pressure are tightly linked in ouabain-dependent hypertension. Our results favor the possibility that enhanced duration of LTP in sympathetic neurons contributes to the increase in sympathetic nerve activity in ouabain-dependent hypertension and suggest that a captopril-sensitive step mediates the link of ouabain with LTP.


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