scholarly journals Effects of tiletamine-xylazine-tramadol combination and its specific antagonist on AMPK in the brain of rats

2019 ◽  
Vol 63 (2) ◽  
pp. 285-292
Author(s):  
Ning Ma ◽  
Xin Li ◽  
Hong-bin Wang ◽  
Li Gao ◽  
Jian-hua Xiao
Keyword(s):  
Mrna Expression ◽  
Opposite Effect ◽  
Brain Regions ◽  
Control Group ◽  
Sprague Dawley ◽  
Sd Rats ◽  
The Central Nervous System ◽  
Specific Antagonist ◽  
Sedation And Analgesia ◽  
The Brain

AbstractIntroduction:Tiletamine-xylazine-tramadol (XFM) has few side effects and can provide good sedation and analgesia. Adenosine 5’-monophosphate-activated protein kinase (AMPK) can attenuate trigeminal neuralgia. The study aimed to investigate the effects of XFM and its specific antagonist on AMPK in different regions of the brain.Material and Methods:A model of XFM in the rat was established. A total of 72 Sprague Dawley (SD) rats were randomly divided into three equally sized groups: XFM anaesthesia (M group), antagonist (W group), and XFM with antagonist interactive groups (MW group). Eighteen SD rats were in the control group and were injected intraperitoneally with saline (C group). The rats were sacrificed and the cerebral cortex, cerebellum, hippocampus, thalamus, and brain stem were immediately separated, in order to detect AMPKα mRNA expression by quantitative PCR.Results:XFM was able to increase the mRNA expression of AMPKα1 and AMPKα2 in all brain regions, and the antagonist caused the opposite effect, although the effects of XFM could not be completely reversed in some areas.Conclusion:XFM can influence the expression of AMPK in the central nervous system of the rat, which can provide a reference for the future development of anaesthetics for animals.

Effects of danshensu on the transforming growth factor-β1/smads signaling pathway in rats with lung injury

2020 ◽  
Vol 10 (11) ◽  
pp. 1816-1823
Author(s):  
Jing Qin ◽  
Xiaoqiang Zhang ◽  
Shengyan Wang ◽  
Yongming Zhang
Keyword(s):  
Lung Injury ◽  
Mrna Expression ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Abdominal Cavity ◽  
Physiological Saline ◽  
Transforming Growth Factor Β1 ◽  
Control Group ◽  
Sprague Dawley ◽  
Sd Rats

Observe the therapeutic effect of Danshensu on lung injury for rats, as well as explore the mechanism of Danshensu in TGF-β1/Smads signaling. Thirty Sprague-Dawley (SD) rats were intratracheally instilled with bleomycin to induce lung injury and interstitial fibrosis. Divided Thirty rats into three groups. DA group (η = 10): Inject 15 mg/kg Danshensu into the abdominal cavity; DXM group (η = 10): Inject 1 mg/kg dexamethasone into the abdominal cavity; BLM group (η = 10): Inject 2 mL physiological saline into the abdominal cavity. Then ten SD rats were intratracheally instilled with physiological saline as normal control group, NC group: Inject 2 mL physiological saline into the abdominal cavity. After a period of 28 days, the degree of pulmonary alveolitis was evaluated using hematoxylin-eosin (HE) staining, and the degree of lung fibrosis was evaluated using Masson?s trichrome (MT) staining. The immunohistochemistry was used to determine the expression of α-SMA. Magnetic nanoparticles+rtQ-PCR was used to determine the mRNA expressions for TGF-β1, Smad3, and Smad7. The alveolitis and pulmonary fibrosis in DA rats were obviously less than those in BLM rats and DXM rats. The expression of α-SMA in DA rats was obviously less than that of in BLM rats and DXM rats; the mRNA expression of TGF-β1 and Smad3 in DA rats were obviously reduced; the Smad7 mRNA expression was obviously up-regulated. DA can alleviate rat lung injury caused by bleomycin. Inhibiting the TGF-β1 and Smad3 mRNA expression, as well as boosting the Smad7 mRNA expression is one of the mechanisms by which Danshensu reduces lung injury.

scholarly journals Intravascular Streaming and Variable Delivery to Brain following Carotid Artery Infusions in the Sprague-Dawley Rat

1988 ◽  
Vol 8 (1) ◽  
pp. 116-120 ◽  
Author(s):  
Stephen C. Saris ◽  
Donald C. Wright ◽  
Edward H. Oldfield ◽  
Ronald G. Blasberg
Keyword(s):  
Carotid Artery ◽  
Temporal Cortex ◽  
Brain Regions ◽  
External Carotid Artery ◽  
External Carotid ◽  
Control Group ◽  
Sprague Dawley ◽  
Intraarterial Infusion ◽  
Sprague Dawley Rats ◽  
The Brain

Intracarotid artery infusions in animals are commonly performed in studies of the blood–brain barrier and in chemotherapy trials. Implicit in the analysis of these experiments is that the infusate will be distributed to the territory of the internal carotid artery in a manner that is proportional to blood flow. Fifteen Sprague-Dawley rats were studied to determine if poor infusate mixing with blood due to intravascular streaming occurred during intracarotid artery drug infusions and if it could be eliminated with fast retrograde infusion. In three experimental groups, a radiolabeled flow tracer—14C-iodoantipyrine (IAP)—was infused retrograde through the external carotid artery into the common carotid artery at slow, medium, and fast rates (0.45, 1.5, and 5.0 ml/min). In a control group, IAP was injected intravenously (i.v.). Local isotope concentrations in the brain were determined by quantitative autoradiography, and the variability of isotope delivery was assessed in the frontoparietal cortex, temporal cortex, and caudate putamen of all animals. Streaming phenomena were manifest in all selected anatomic areas after the slow and medium rates of intraarterial infusion. After fast intracarotid infusion or i.v. injection, there was uniform distribution of isotope in the same brain regions.

scholarly journals Synergistic suppression of pre-perfusion of donor livers with recipient serum and cobra venom factor treatment on hyperacute rejection following liver xenotransplantation

2012 ◽  
Vol 27 (5) ◽  
pp. 301-305 ◽  
Author(s):  
Baohua Zhu ◽  
Chuanming Tong ◽  
Weitao Guo ◽  
Rong Pu ◽  
Guoping Zhang ◽  
...  
Keyword(s):  
Survival Time ◽  
Hyperacute Rejection ◽  
Cobra Venom ◽  
Control Group ◽  
Sprague Dawley ◽  
Donor Liver ◽  
Cobra Venom Factor ◽  
Sd Rats ◽  
Sprague Dawley Rats ◽  
And Control

PURPOSE: To investigate synergistic suppression of donor liver pre-perfusion with recipient serum (RS) and cobra venom factor (CVF) treatment on hyperacute rejection (HAR) following liver xenotransplantation. METHODS: Guinea-pigs (GP, n=24) and Sprague-Dawley rats (SD, n=24) were recruited. Before transplantation, serum was collected from SD rats and used for preparation of inactivated complements. GP and SD rats were randomly assigned into four groups (n=6), respectively: RS group, CVF group, RS+CVF group and control group. Orthotopic liver xenotransplantation was performed with modified two-cuff technique. The survival time and liver function of recipients, morphological and pathological changes in rat livers were investigated. RESULTS: There was no piebald like change in the recipient livers in all experiment groups. The survival time of recipients in all experiment groups was longer than that in control group (p<0.05). Moreover, the survival time in the RS+CVF group was markedly longer than that in the RS group (p<0.01) and CVF group (p<0.05). The serum ALT level in all experiment groups were lower than that in the control group (p<0.05). Furthermore, the ALT level in the RS+CVF group was significantly lower than that in the CVF group (p<0.05) and RS group (p<0.01). The histological damages were significantly improved when compared with the control group, and the histological damages in the RS+CVF group were milder than those in the remaining groups (p<0.05) CONCLUSION: Pre-perfusion of donor liver with recipient serum and cobra venom factor treatment can exert synergistic suppressive effects on the hyperacute rejection following liver xenotransplantation.

Refining the Effects Observed in a Developmental Neurobehavioral Study of Ammonium Perchlorate Administered Orally in Drinking Water to Rats. II. Behavioral and Neurodevelopment Effects

2005 ◽  
Vol 24 (6) ◽  
pp. 451-467 ◽  
Author(s):  
Raymond G. York ◽  
John Barnett ◽  
Michael F. Girard ◽  
David R. Mattie ◽  
Marni V. K. Bekkedal ◽  
...  
Keyword(s):  
Drinking Water ◽  
Ammonium Perchlorate ◽  
Brain Regions ◽  
Male Rats ◽  
Male Rat ◽  
Sprague Dawley ◽  
Continuous Access ◽  
Brain Morphometry ◽  
The Central Nervous System ◽  
The Right

A developmental neurotoxicity study was conducted to generate additional data on the potential functional and morphological hazard to the central nervous system caused by ammonium perchlorate in offspring from in utero and lactation exposure. Female Sprague-Dawley rats (23 to 25/group) were given continuous access to 0 (carrier), 0.1, 1.0, 3.0, and 10.0 mg/kg-day perchlorate in the drinking water beginning 2 weeks prior to mating and continuing through day 10 of lactation for the behavioral function assessment or given continuous access to 0 (carrier), 0.1, 1.0, 3.0, and 30.0 mg/kg-day beginning on gestation day 0 and continuing through day 10 of lactation for neurodevelopment assessments. Motor activity was conducted on postpartum days 14, 18, and 22 and juvenile brain weights, neurohistopathological examinations, and regional brain morphometry were conducted on postpartum days 10 and 22. This research revealed a sexually dimorphic response, with some brain regions being larger in perchlorate-treated male rats than in comparable controls. Even so, there was no evidence of any obvious exposure-related effects on male rat brain weights or neuropathology. The most consistent exposure-related effect in the male pups was on the thickness of the corpus callosum, with both the right- and left-sided measures of the thickness of this white matter tract being significantly greater for the male pups in the 0.1 and 1.0 mg/kg-day exposure groups. The behavioral testing suggests prenatal exposure to ammonium perchlorate does not affect the development of gross motor movements in the pups.

scholarly journals Quantitative Analysis of Diffusion Tensor Imaging in Chronic Hepatitis in Rats

2020 ◽  
Author(s):  
Mengping Huang ◽  
Xin Lu ◽  
Xiaofeng Wang ◽  
Jian Shu
Keyword(s):  
Chronic Hepatitis ◽  
Diffusion Tensor Imaging ◽  
Liver Fibrosis ◽  
Diffusion Tensor ◽  
Control Group ◽  
Sprague Dawley ◽  
Subcutaneous Injections ◽  
Sprague Dawley Rats ◽  
Pathological Stages ◽  
The Brain

Abstract Background Diffusion tensor imaging (DTI) is mainly used for detecting white matter fiber in the brain. From this, DTI has been applied to assess fiber in liver disorders by prior studies. But non-sufficient data has been obtained if DTI could be used for exactly staging chronic hepatitis. This study is to assess the value of DTI for staging of liver fibrosis (F), necroinflammatory activity (A), and steatosis (S) of chronic hepatitis in rats. Methods Seventy male Sprague-Dawley rats were divided into control group(n = 10) and experimental group(n = 60). The rat models of chronic hepatitis were established by abdominal subcutaneous injections of 40% CCl4. All rats underwent 3.0T MRI. ROIs were placed on DTI to estimate MR parameters (rADC value and FA value). Histopathology was the reference standard. Multiple linear regression was used to analyze the association between MR parameters and pathology. The differences in rADC value and FA value among pathological stages were evaluated by MANOVA or ANOVA. LSD was used to test the differences between each two groups. ROC analysis was performed. Results The numbers of each pathology were as follows: F0(n = 15), F1(n = 11), F2(n = 6), F3(n = 9), F4(n = 6); A0(n = 8), A1(n = 16), A2(n = 16), A3(n = 7); S0(n = 10), S1(n = 7), S2(n = 3), S3(n = 11), S4(n = 16). The rADC value had a negative correlation with liver fibrosis (r=-0.392, P = 0.008) and inflammation (r=-0.359, P = 0.015). FA value had a positive correlation with fibrosis (r = 0.409, P = 0.005). Significant differences were found in FA value between F4 and F0 ~ F3 (P = 0.03), while no significant differences among F0 ~ F3 were found (P > 0.05). AUC of FA value in differentiating F4 from F0 ~ F3 was 0.909(p < 0.001) with 83.3% Sensitivity, 85.4% specificity when the FA value was at the cut-off of 588.089(× 10− 6mm2/s). Conclusion FA value for DTI can distinguish early cirrhosis from normal, mild and moderate liver fibrosis.

scholarly journals Analysis of electrogenesis’ changes in mental retardation persons by using computer electroencephalography

2021 ◽  
Vol 11 (11) ◽  
pp. 249-265
Author(s):  
B. Lobasyuk ◽  
L. Bartsevich ◽  
A. Zamkovaya
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mental Retardation ◽  
Theta Rhythm ◽  
Cognitive Activity ◽  
Control Group ◽  
Bioelectrical Activity ◽  
The Central Nervous System ◽  
Beta Rhythms ◽  
The Brain

Justification. Mental retardation is a persistent decrease in human cognitive activity against the background of organic damage to the central nervous system. Neurophysiological diagnostics, in particular electroencephalography (EEG), most adequately reflects the morpho-functional state of the central nervous system, which is the basis of the mechanisms of mental activity, and the originality of the bioelectrical activity of the brain can be considered as the main indicator that determines a decrease in the level of intellectual development and, thereby, characterizes this state. This provision actualizes the search for highly informative indicators of the originality of the bioelectrical activity of the brain in children with intellectual disabilities. Purspose. With the use of periodometric analysis investigate EEG’s indicators and interhemispheric asymmetry of rhythms amplitudes in MR patients. Materials and methods. The EEG was recorded in a state of calm wakefulness with closed eyes with Neuron-Spectrum-2 electroencephalograph. Differences in indicators were tracked using the calculation of the coefficient of compliance (CC), EEG functional asymmetry coefficients in amplitude were determined, too. Results. It was revealed that in MR patients the amplitudes of the rhythms were greater than in healthy subjects. The greatest increase was determined in theta rhythm in the anterior temporal and posterior temporal leads in the left hemispheres. Duration indices in the delta, theta and alpha ranges of the EEG in mental retardation compared with the control group were increased, and the indices of the duration of beta rhythms - decreased. When analyzing FMPA in MR persons it turned out that in right-handers the negativeness of FMPA indices increased, and in left-handers there was an increase in the positivity of FMPA indices. Conclusions 1. With mental retardation, the amplitudes of the rhythms were greater than in healthy people. The greatest increase was determined in theta rhythm in the anterior temporal and posterior temporal leads in the left hemispheres. 2. The indices of duration in the delta, theta and alpha ranges of the EEG of MR subjects were increased, and the indices of the duration of beta rhythms – decreased. 3. When analyzing FMPA in MR persons, it turned out that in right-handers the negativeness of FMPA indices increased, and in left-handers there was an increase in the positivity of FMPA indices.

Abstract 17: Early Life Stress Sensitizes The Angiotensin II-elicited Hypertensive Response

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Baojian Xue ◽  
Terry Beltz ◽  
Fang Guo ◽  
David M Pollock ◽  
Jennifer S Pollock ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Proinflammatory Cytokines ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Male Rats ◽  
Sprague Dawley ◽  
Cns Inflammation ◽  
Wide Range ◽  
The Brain

Separation of neonatal rodent pups from their mothers has been used as a model to study the effects of early life stress (ELS) on behavioral and physiological responses in adults. Using an Induction-Delay-Expression experimental paradigm, our previous studies demonstrate that a wide range of stressors administered during an induction period produces hypertensive response sensitization (HTRS) in response to a subsequent pro-hypertensive stimulus. HTRS is accompanied by activation of the brain renin-angiotensin system (RAS) and CNS inflammation. The present study investigated whether ELS induces HTRS and changes in brain-related underlying mechanisms. Rat neonates from Sprague-Dawley breeders were subjected to ELS by separating them each morning from their mothers for 3 h on postnatal days 2 to 14. Pups from non-handled litters formed control groups. At 10 weeks of age, male rats were used to evaluate blood pressure and autonomic function using telemetric probes and pharmacological methods. In addition, in separate control and ELS groups, the lamina terminalis (LT) structures and the hypothalamic paraventricular nucleus (PVN) were analyzed for mRNA expression of RAS components and proinflammatory cytokines. Adult ELS rats as compared to non-separated controls exhibited 1) HTRS during expression testing using 2 week ANG II infusions (120 ng/kg/min s.c.; ELS animals, Δ45.5±4.5 mmHg vs. controls, Δ22.4±3.1 mmHg); 2) a greater reduction in mean arterial pressure following ganglionic blockade (hexamethonium, 30 mg/kg, ip), 3) increased sympathetic drive to the heart (atenolol, 8 mg/kg, ip), 4) decreased vagal tone (atropine, 8 mg/kg, ip), and 5) increased mRNA expression of several components of the brain RAS and proinflammatory cytokines in the LT and PVN. These results suggest that maternal ELS may predispose individuals to hypertension that is mediated by upregulation of the brain RAS and proinflammatory cytokines and increased sympathetic drive to the cardiovascular system.

P3486Experimental model for heart failure in rats: apelin-13/apj and bnp-45 gene expression analysis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H R Helmi ◽  
A P Sunjaya ◽  
D Limanan ◽  
A R Prijanti ◽  
S W A Jusman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Mrna Expression ◽  
Rat Model ◽  
Control Group ◽  
P Value ◽  
Sprague Dawley ◽  
Hypoxia Exposure ◽  
Systemic Hypoxia

Abstract Background Apelin, an adipokine peptide and its receptor has recently emerged as a key signaling pathway in maintaining cardiac performance at chronic pressure loads. Apelin has been linked to ventricular dysfunction and therefore maybe of pathophysiologic relevance as a candidate biomarker in HF patients. Purpose This study aims to investigate Apelin-13 gene expression and level, and Apelin receptor (APJ) level in a rat model of heart failure induced by chronic systemic hypoxia and their correlation to BNP-45 gene expression and level, the current gold standard biomarker for heart failure, and to cardiac histopathologic changes. The effect of chronic systemic hypoxia on cardiac hypertrophy, remodeling and heart failure parameters is also of interest. Methods Twenty-eight male Sprague-Dawley rats (8–12 weeks of age) were placed in special hypoxic chambers divided into 7 groups – a control group provided with normoxia (atmospheric O2 levels) and 6 exposure groups exposed to hypoxia (8% O2) for 6 hours, 1, 3, 5, 7 and 14 days respectively prior to measurement. Changes in the expression of Apelin and BNP-45 were measured using quantitative real-time PCR, whereas changes in Apelin-13, APJ and BNP-45 levels were measured using ELISA. Histopathology staining using Hematoxylin and Eosin was performed on cardiac tissues post-termination. Results Compared to control, BNP-45 mRNA expression in the hypoxic heart was only significantly different in day 14, whereas, Apelin mRNA expression had showed significantly higher values starting from day 7 onward. This is in line with the evidence of cardiac hypertrophy based on histopathologic examination present from day 7 onwards. BNP-45 and Apelin-13 levels were significantly higher compared to control from day 5 onwards with a peak on day 7. Although significantly higher than control, Apelin-13 and BNP-45 level decreases in day 14 as compared to day 7. Mean APJ levels showed a similar profile with Apelin-13 and BNP-45 levels with a peak in day 7 (4.619 ng/mL). The cardiac Apelin-13 level shows strong significant correlation with BNP-45 levels (r 0.823, p-value 0.0001). There was also a strong significant correlation between APJ receptor levels with Apelin-13 (r 0.9029, p-value 0.001) and BNP-45 (r 0.9062, p-value 0.0009) levels. Apelin-13, APJ and BNP-45 levels also showed strong significant positive correlation to the duration of hypoxia exposure. Conclusion Chronic (≥5 days) and not acute systemic hypoxia in an experimental rat model leads to increase in Apelin-13, APJ and BNP-45 levels. Apelin-13 and BNP-45 were found to significantly increase from 5 days onwards. Apelin mRNA expression was found to show significant increase earlier compared to BNP-45 mRNA expression. Hence, Apelin may serve as a new candidate biomarker for detection of HF due to oxidative stress compared to BNP-45. Exposure to chronic systemic hypoxia can serve as an easily replicable rat model for heart failure. Acknowledgement/Funding Department of Biochemistry and Molecular Biology, Faculty of Medicine, Tarumanagara University, Jakarta, Indonesia

Dexmedetomidine elevates the lethal dose threshold of bupivacaine in rats: A dosing study

2019 ◽  
Vol 39 (3) ◽  
pp. 365-373
Author(s):  
L Pan ◽  
Y Zhang ◽  
Y He ◽  
Z Chen ◽  
S Wang ◽  
...  
Keyword(s):  
Femoral Vein ◽  
Lethal Dose ◽  
Control Group ◽  
Sprague Dawley ◽  
Dose Threshold ◽  
Sd Rats ◽  
Group 12 ◽  
Group 3 ◽  
The Right ◽  
Group 1

Dexmedetomidine (DMED), an alpha-2 adrenoreceptor agonist, has been widely used in regional anesthesia procedures. However, the effect of DMED on local anesthetic cardiotoxicity has not been well delineated. This study consisted of two experiments. In experiment A, 42 Sprague–Dawley (SD) rats were randomly divided into 6 groups ( n = 7), each group was pretreated with DMED 0 μg kg−1 (D0 group), 1 μg kg−1 (D1 group), 3 μg kg−1 (D3 group), 6 μg kg−1 (D6 group), 12 μg kg−1 (D12 group), and 24 μg kg−1 (D24 group), administered through the right femoral vein. In experiment B, 20 SD rats were randomly divided into 4 groups ( n = 5), such as control group, DMED group, yohimbine (YOH) group, and DMED + YOH group. Each subgroup in experiment B was also pretreated similarly as in experiment A. After pretreatment of rats as described above (in experiments A and B), bupivacaine 2.5 mg kg−1 min−1 was infused to induce cardiac arrest. In experiment A, the lethal dose threshold of bupivacaine and plasma bupivacaine concentration in D3 and D6 group were higher than the other groups. In experiment B, there was no interaction between DMED and YOH in lethal dose threshold, arrhythmia time, plasma concentration of bupivacaine, and myocardial content of bupivacaine. DMED doses of 3–6 μg kg−1 elevated the lethal dose threshold of bupivacaine without involvement of the alpha-2 adrenoceptors.

scholarly journals Letrozole-Induced Polycystic Ovary Syndrome Attenuates Cystathionine-β Synthase Gene Expression in the Ovaries of Female Sprague Dawley Rats

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1244-1244
Author(s):  
Amanda Bries ◽  
Joe Webb ◽  
Brooke Vogel ◽  
Claudia Carrillo ◽  
Aileen Keating ◽  
...  
Keyword(s):  
Gene Expression ◽  
Polycystic Ovary Syndrome ◽  
Mrna Expression ◽  
Polycystic Ovary ◽  
Elevated Serum ◽  
Reproductive Age ◽  
Sprague Dawley ◽  
Polycystic Ovaries ◽  
Ovary Syndrome ◽  
Sd Rats

Abstract Objectives Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects 10% of reproductive age women and leads to hyperandrogenism, abnormal menstrual cycles, and polycystic ovaries. Moreover, PCOS has been associated with elevated serum homocysteine; however, the characterization of one-carbon metabolism (OCM) in PCOS remains incomplete. The aim of our research was to examine OCM in a genetic and chemically-induced rodent model of PCOS: 1) viable yellow Agouti (Avy) mice; and 2) letrozole (Let)-induced Sprague Dawley (SD) rats. Methods Five wk old female Avy mice (N = 18), their lean controls (N = 18), and SD rats (N = 36) were acclimated for one wk. Following acclimation, the animals were placed on a modified standard AIN93G diet (energy, %: 50.4, carbohydrate; 17.3, protein; and 32.3, fat). Rats were randomly assigned to Let (1 g/kg BW) treatment or vehicle (carboxymethylcellulose) control that was administered via a subcutaneously implanted slow-release pellet every 30-d. For both models, 12 animals were randomly assigned to be euthanized during proestrus at one of the following ages: 8, 16 or 24 wk. Bodyweight and estrous cycles were measured daily. Ovaries were collected to assess gene expression of OCM. These data were analyzed using linear mixed models to determine the main effects of age and treatment at a significance level of P &lt; 0.05. Results Letrozole significantly reduced the occurrence of proestrus and estrus stages (P = 0.0001 and P = 0.006, respectively). Additionally, Let-induced rats had increased BW compared to control rats, across all age groups (P &lt; 0.0001). In contrast, Avy mice weighed less than their controls by 24 wk of age (P &lt; 0.0001). Cystathionine-β synthase (CBS) mRNA expression was downregulated in the Let-induced vs. control rats at 16 (59%; P &lt; 0.05) and 24 (77%; P &lt; 0.01) wk of age. As expected, Cyp19A1, aromatase mRNA was downregulated in the Let-induced rats (P = 0.02). Interestingly, betaine-homocysteine s-methyltransferase (BHMT) mRNA increased as a function of age in Let-induced rats (P = 0.03). Conclusions These data demonstrate that Letrozole-induced PCOS temporally decreases ovarian CBS mRNA expression; whereas, BHMT mRNA is upregulated as a function of age. Funding Sources This work was supported by the National Institute of Child Health and Human Development.

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