Adult Female Rats Research Articles

Effect of vitamin D3 supplementation on blood parameters and liver gene expression in female rats.

To better understand the molecular mechanism responsible for the therapeutic potential of vitamin D, we conducted an analysis of the liver transcriptomes of adult female rats. Adult female rats (n = 18) were divided into three groups, receiving different doses of vitamin D: group I, 0; group II, 1000 U/kg; and group III, 5000 U/kg. Growth, body weight, the weight of main organs, blood haematological and biochemical parameters were evaluated. Gene expression in the liver were analyzed using RNA-seq and qPCR techniques. We observed a lower platelet count (p < 0,008) and a significantly greater (p < 0.02) number of WBCs in rats supplemented with 1000 U/kg than in rats from group III (5000 U/kg). Moreover, we noted a trend (p < 0.06) in total cholesterol concentration, suggesting a linear decrease with increasing doses of vitamin D. RNA-seq analysis did not reveal any differentially expressed genes with FDR < 0.05. However, GSEA revealed significant activation of a number of processes and pathways, including: "metallothionein, and TspO/MBR family", and "negative regulation of tumor necrosis factor production". qPCR analysis revealed significant upregulation of the Mt1, Mt2 and Orm1 genes in animals receiving high doses of vitamin D (p < 0.025, p < 0.025, and p < 0009, respectively). Moreover, Srebp2 and Insig2 were significantly lower in both experimental groups than in the control group (p < 0.003 and p < 0.036, respectively). Our results support the anti-inflammatory, anitioxidant and anticholesterologenic potential of vitamin D but suggest that high doses of vitamin D are needed to obtain significant results in this regard.

Insulin signaling and mitochondrial phenotype of skeletal muscle are programmed in utero by maternal diabetes

Maternal diabetes may influence glucose metabolism in adult offspring, an area with limited research on underlying mechanisms. Our study explored the impact of maternal hyperglycemia during pregnancy on insulin resistance development. Adult female Sprague-Dawley rats from control and diabetic mothers were mated, and their female offspring were monitored for 150 days. The rats were euthanized for blood and muscle samples. Maternal diabetes led to heightened insulin levels, increased HOMA-IR, elevated triglycerides, and a raised TyG index in adult offspring. Muscle samples showed a decreased protein expression of AMPK, PI3K, MAPK, DRP1, and MFF. These changes induced intergenerational metabolic programming in female pups, resulting in insulin resistance, dyslipidemia, and glucose intolerance by day 150. Findings highlight the offspring’s adaptation to maternal hyperglycemia, involving insulin resistance, metabolic alterations, the downregulation of insulin signaling sensors, and disturbed mitochondrial morphology. Maintaining maternal glycemic control emerges as crucial in mitigating diabetes-associated disorders in adult offspring.

Evaluation of Ovarian Histomorphology and Function Following Clomiphene Citrate and Human Chorionic Gonadotropin Administration in Wistar Rats

Polycystic ovarian syndrome (PCOS), affecting 5-10% of women, is a leading cause of infertility affecting 10-15% of couples globally. Human chorionic gonadotropin (hCG) and clomiphene citrate (CC) are often utilized for the treatment of PCOS. Accordingly, this study explored the effects of CC and hCG on ovarian histomorphology and fertility parameters. Twenty adult female rats were divided into four groups as follows: Group A (control) received only feed and water; Group B received 0.7 mg/kg BW of CC twice daily for five days and was mated before sacrifice on day 19 (before litter); Group C received 0.7 mg/kg BW of CC twice daily for five days, followed by mating and allowed to litter before sacrifice; Group D received 0.7 mg/kg body weight (BW) of hCG on day one, followed by 0.7 mg/kg BW of CC twice daily for five days, and were mated before sacrifice on day 7 (before litter). Results showed that Group B rats had higher, more than other groups, Follicle-stimulating hormone (FSH), Estradiol, Testosterone and Prolactin levels when compared to the control. Similarly, rats in Group B had higher levels of Progesterone while Group D had higher levels of Luteinizing hormone (LH) when compared to the control group. Histological findings demonstrated diverse impacts on ovarian structures, ranging from congested blood vessels to haemorrhages and follicular cysts. Consequently, this study underscores the complexities of drug interactions in reproductive health and provides preliminary insights into the possible adverse effects of CC and hCG on the ovary and fertility parameters.

Increased Beneficial Outcome of Insulin by Medical Ozone against Experimentally Diabetic Rats

The present research aimed to determine the effective dose of medical ozone on some blood parameters in experimental diabetic rats.48 adult female rats with (a 180 - 200 g) weight average were randomly divided into (6) groups (n=8): control (T1), Medical ozone (MO) (T2), diabetic (T3), ozone-treated diabetic (T4), insulin-treated diabetic(T5), and MO, insulin-treated diabetic (T6). Diabetes was induced by an intraperitoneal injection of a single dose of Alloxan (150 mg/kg of the body weight). The diabetic rats were left for 2 days to assure the stability of diabetes in them, before continuing experiments. The results of RBCs in groups (T2, T4, T5, and T6) showed a significant increase compared with the diabetic group and control group, and Hb and WBCs parameters showed a significant decrease in (T3, T4, and T5)When compared with other groups. The results of the platelet count there was a significant increase in (T3, T4, and T5) compared to the control group. Clotting time and calcium ions recorded a significant decrease in all treated diabetic groups (T3, T4, T5, and T6) when compared with (T1 and T2), at the same time, the results of bleeding time recorded a significant decrease in (T3 and T4 ) compared with the other groups while (T4 and T5) showed non-significant difference compared to (T1 and T2). The current study concluded that the treatment combination of medical ozone and insulin has ameliorative effects on some blood parameters except clotting time and calcium, ions.

Electrical stimulation of the cuneiform nucleus enhances the effects of rehabilitative training on locomotor recovery after incomplete spinal cord injury.

Most human spinal cord injuries are anatomically incomplete, leaving some fibers still connecting the brain with the sublesional spinal cord. Spared descending fibers of the brainstem motor control system can be activated by deep brain stimulation (DBS) of the cuneiform nucleus (CnF), a subnucleus of the mesencephalic locomotor region (MLR). The MLR is an evolutionarily highly conserved structure which initiates and controls locomotion in all vertebrates. Acute electrical stimulation experiments in female adult rats with incomplete spinal cord injury conducted in our lab showed that CnF-DBS was able to re-establish a high degree of locomotion five weeks after injury, even in animals with initially very severe functional deficits and white matter lesions up to 80-95%. Here, we analyzed whether CnF-DBS can be used to support medium-intensity locomotor training and long-term recovery in rats with large but incomplete spinal cord injuries. Rats underwent rehabilitative training sessions three times per week in an enriched environment, either with or without CnF-DBS supported hindlimb stepping. After 4 weeks, animals that trained under CnF-DBS showed a higher level of locomotor performance than rats that trained comparable distances under non-stimulated conditions. The MLR does not project to the spinal cord directly; one of its main output targets is the gigantocellular reticular nucleus in the medulla oblongata. Long-term electrical stimulation of spared reticulospinal fibers after incomplete spinal cord injury via the CnF could enhance reticulospinal anatomical rearrangement and in this way lead to persistent improvement of motor function. By analyzing the spared, BDA-labeled giganto-spinal fibers we found that their gray matter arborization density after discontinuation of CnF-DBS enhanced training was lower in the lumbar L2 and L5 spinal cord in stimulated as compared to unstimulated animals, suggesting improved pruning with stimulation-enhanced training. An on-going clinical study in chronic paraplegic patients investigates the effects of CnF-DBS on locomotor capacity.

Human α-synuclein overexpression upregulates SKOR1 in a rat model of simulated nigrostriatal ageing.

Parkinson's disease (PD) is characterised by progressive loss of dopaminergic (DA) neurons from the substantia nigra (SN) and α-synuclein (αSyn) accumulation. Age is the biggest risk factor for PD and may create a vulnerable pre-parkinsonian state, but the drivers of this association are unclear. It is known that ageing increases αSyn expression in DA neurons and that this may alter molecular processes that are central to maintaining nigrostriatal integrity. To model this, adult female Sprague-Dawley rats received a unilateral intranigral injection of adeno-associated viral (AAV) vector carrying wild-type human αSyn (AAV-αSyn) or control vector (AAV-Null). AAV-αSyn induced no detrimental effects on motor behaviour, but there was expression of human wild-type αSyn throughout the midbrain and ipsilateral striatum at 20 weeks post-surgery. Microarray analysis revealed that the gene most-upregulated in the ipsilateral SN of the AAV-αSyn group was the SKI Family Transcriptional Corepressor 1 (SKOR1). Bioenergetic state analysis of mitochondrial function found that SKOR1 overexpression reduced the maximum rate of cellular respiration in SH-SY5Y cells. Furthermore, experiments in SH-SY5Y cells revealed that SKOR1 overexpression impaired neurite growth to the same extent as αSyn, and inhibited BMP-SMAD-dependent transcription, a pathway that promotes DA neuronal survival and growth. Given the normal influence of ageing on DA neuron loss in human SN, the extent of αSyn-induced SKOR1 expression may influence whether an individual undergoes normal nigrostriatal ageing or reaches a threshold for prodromal PD. This provides new insight into mechanisms through which ageing-related increases in αSyn may influence molecular mechanisms important for the maintenance of neuronal integrity.

Mode of delivery alters sensitivity to thermal and chemical stimuli in adult rats: An experimental study.

The mode of delivery might prompt a long-lasting alteration in physiological and behavioral responsiveness in offspring. This study was intended to evaluate if the mode of delivery could alter sensitivity to thermal and chemical stimuli in female rats. 56 adult female Wistar rats (200-220 gr) that were born by vaginal or cesarean section (C-section) were used (n = 28/each). Inflammatory pain was induced by subcutaneous injection of formalin into the hind paw. The thermal nociceptive threshold was determined by tail-flick and hot plate tests. Besides, the Western blot test was used to evaluate the spinal cord levels of c-Fos and c-Jun proteins. Formalin-induced inflammation was significantly decreased in C-section group as compared to vaginally born rats (p 0.001). The baseline nociceptive threshed and morphine-induced analgesia were significantly increased in C-section groups in comparison to vaginally born rats. In addition, the levels of c-Fos and c-Jun proteins were significantly decreased in the spinal cord of C-section rats as compared to vaginally born animals (p 0.01). Morphine treatment could decrease the expression of c-Fos and c-Jun in the C-section group (p 0.05). Overall, C-section rats showed lower spinal nociceptive processing and neuronal activity later in life, compared to the vaginal born rats.

Adolescent activity-based anorexia has a substantial and prolonged impact on social behavior in young adult female rats

Activity-based anorexia (ABA) is a rodent model of anorexia nervosa (AN) that induces several key components of AN, including voluntary reduction in food intake, reduced body weight, hyperactivity, and alterations to the hypothalamic-pituitary-adrenal (HPA) axis. Previous research has demonstrated persistently increased anxiety-like behavior in the elevated plus maze (EPM), a test measuring avoidance of novel and open areas in adult female rats that experienced ABA during adolescence and are weight-restored in adulthood. Whether the same behavioral effects of two bouts of adolescent ABA emerge in response to different anxiety-provoking stimuli, however, has not been explored. We used the social partition (SP), novelty suppressed feeding (NSF), marble burying, and EPM tests to explore whether two bouts of adolescent ABA have persistent effects on anxiety-like behavior in weight restored young adult female rats. One-way ANOVA analyses revealed that female rats that experienced two bouts of ABA during adolescence had increased anxiety-like behavior in the EPM and SP tests in young adulthood following weight restoration compared with controls. These data demonstrate that the enduring behavioral effects of two bouts of adolescent ABA are specific to particular anxiety-provoking stimuli and suggest that adolescent ABA has enduring effects on social relationships.

Antioxidative Effects of Hydro-Alcoholic Extract and Essential Oil of Quercus brantii Exerts Anti-Depressant-Like Effect and Improvement of Memory Defect in Progesterone-Induced Postpartum Depression in Rats

Background: Depression and memory disorders are known to be associated with increased oxidative stress. There is evidence suggesting that Quercus brantii (Q. brantii) possesses antioxidant properties. Objectives: This study aims to investigate the impact of Q. brantii hydro-alcoholic extract and oil on cognitive dysfunction in a postpartum depression (PPD) model and on oxidant/antioxidant activity in the hippocampus of adult female rats. Methods: Forty-two female Wistar rats (200 - 250 g) were randomly divided into six groups. PPD was induced by chronic intraperitoneal administration (5 days) of progesterone at a dose of 5 mg/kg, and three days after discontinuation, depressive behavior was assessed using a forced swimming test. Simultaneously, Quercus brantii hydro-alcoholic extract (100 mg/kg) and oil (45%) were administered. Spatial memory and locomotor activity were evaluated 24 hours after training using the Morris water maze and open field tests, respectively. The hippocampus tissue of all rats was used to evaluate oxidant-antioxidant factors, Vitamin D, and corticosterone levels. Results: Quercus brantii extract significantly reduced depression (P &lt; 0.05). Treatment with Q. brantii extract and oil improved spatial memory and learning (P &lt; 0.05). The Q. brantii extract increased levels of SOD, GSH, catalase, and vitamin D while decreasing MDA levels; additionally, Q. brantii oil increased SOD and vitamin D levels and decreased MDA levels in the brain (P &lt; 0.05). Conclusions: Quercus brantii extract and oil appear to have beneficial effects on learning and memory impairment in a PPD-induced model, which may be associated with their biochemical effects on the brain.

The neuroprotective effect of exogen melatonin upon fetal hippocampus damage caused by high-dose caffeine administration in pregnant rats.

The aim of this study is to evaluate whether exogenous melatonin (MEL) mitigates the deleterious effects of high-dose caffeine (CAF) administration in pregnant rats upon the fetal hippocampus. A total of 32 adult Wistar albino female rats were divided into four groups after conception (n = 8). At 9-20 days of pregnancy, intraperitoneal (i.p.) MEL was administered at a dose of 10mg/kg/day in the MEL group, while i.p. CAF was administered at a dose of 60 mg/kg/day in the CAF group. In the CAF plus MEL group, i.p. CAF and MEL were administered at a dose of 60 and 10mg/kg/day, respectively, at the same period. Following extraction of the brains of the fetuses sacrificed on the 21st day of pregnancy, their hippocampal regions were analyzed by hematoxylin and eosin and Cresyl Echt Violet, anti-GFAP, and antisynaptophysin staining methods. While there was a decrease in fetal and brain weights in the CAF group, it was found that the CAF plus MEL group had a closer weight average to that of the control group. Histologically, it was observed that the pyramidal cell layer consisted of 8-10 layers of cells due to the delay in migration in hippocampal neurons in the CAF group, while the MEL group showed similar characteristics with the control group. It was found that these findings decreased in the CAF plus MEL group. It is concluded that high-dose CAF administration causes a delay in neurogenesis of the fetal hippocampus, and exogenous MEL is able to mitigate its deleterious effects.

Effects of melatonin and metformin on the ovaries of rats with polycystic ovary syndrome

To study the combined and isolated effects of melatonin and metformin in the ovarian tissue of rats with PCOS. Experimental study using a rat model of PCOS induced by continuous light exposure. Forty adult female rats were divided into 5 groups: physiological estrus phase (Sham); permanente estrus with PCOS induced by continuous lighting exposure for 60 consecutive days (control); with PCOS treated with melatonin; with PCOS treated with metformin; with PCOS treated with melatonin + metformin. After 60 days of treatments, all rats were killed, and ovaries were collected and processed for paraffin-embedding. Formalin-fixed paraffin-embedded sections were stained with hematoxylin and eosin or subjected to immunohistochemistry for proliferation (Ki-67) and apoptosis (cleaved caspase 3) detection markers. Federal University of São Paulo, Brazil. Forty adult female Wistar rats (Rattus norvegicus albinus). Number of corpus luteum and ovarian cysts, number of ovarian follicles (primary and antral follicles), number of interstitial cells, percentage of ovarian follicles (primary and antral follicles), and of interstitial cells immunostained to cleaved caspase-3 and Ki-67. Absence of corpus luteum, a higher number of cysts, and increased nuclear volume and area of interstitial cells, along with a decrease in primary and antral follicle numbers, were noticed in the control group compared with the Sham group. Melatonin and metformin treatments attenuated these effects, although the combined treatment did not mitigate the increased number of cysts and ovaries induced by PCOS. An increase in theca interna cell apoptosis was observed in the control group, whereas melatonina and metformin treatments reduced it significantly. A higher percentage of caspase-3-immunostained granulosa cells was noted in the Sham and all treated groups compared with the control group; no aditive effects on ovarian cell apoptosis were observed in the combined treatment. The percentage of Ki-67- immunostained granulosa cells was significantly higher in the control group compared with the Sham group. However, the combined treatment, not melatonin and metformin alone, mitigated this effect. A higher percentage of Ki-67-immunostained interstitial cells was observed in all treated groups compared with the Sham and control groups, whereas no additive effects in that immunoreactivity were observed in the combined treatment. Melatonin and metformin may improve ovarian function in rats with PCOS. The combined melatonin and metformin treatment is more effective in attenuating excessive granulosa cell proliferation, but it is not more effective in improving ovarian function than these drugs applied alone in rats with PCOS.

Acute ampakines increase voiding function and coordination in a rat model of SCI.

Neurogenic bladder dysfunction causes urological complications and reduces the quality of life in persons with spinal cord injury (SCI). Glutamatergic signaling via AMPA receptors is fundamentally important to the neural circuits controlling bladder voiding. Ampakines are positive allosteric modulators of AMPA receptors that can enhance the function of glutamatergic neural circuits after SCI. We hypothesized that ampakines can acutely stimulate bladder voiding that has been impaired due to thoracic contusion SCI. Adult female Sprague-Dawley rats received a unilateral contusion of the T9 spinal cord (n = 10). Bladder function (cystometry) and coordination with the external urethral sphincter (EUS) were assessed 5 d post-SCI under urethane anesthesia. Data were compared to responses in spinal-intact rats (n = 8). The 'low-impact' ampakine CX1739 (5, 10, or 15 mg/kg) or vehicle (2-hydroxypropyl-beta-cyclodextrin [HPCD]) was administered intravenously. The HPCD vehicle had no discernible impact on voiding. In contrast, following CX1739, the pressure threshold for inducing bladder contraction, voided volume, and the interval between bladder contractions were significantly reduced. These responses occurred in a dose-dependent manner. We conclude that modulating AMPA receptor function using ampakines can rapidly improve bladder-voiding capability at subacute time points following contusion SCI. These results may provide a new and translatable method for therapeutic targeting of bladder dysfunction acutely after SCI.

Targeting Aquaporin-5 by Phosphodiesterase 4 Inhibition Offers New Therapeutic Opportunities for Ovarian Ischemia Reperfusion Injury in Rats

This study aimed to examine the effect of Phosphodiesterase 4 (PDE4) inhibition on Aquaporin-5 (AQP5) and its potential cell signaling pathway in the ovarian ischemia reperfusion (OIR) model. Thirty adult female rats were divided into five groups: Group 1; Control: Sham operation, Group 2; OIR that 3 hour ischemia followed by 3 hour reperfusion, Group 3; OIR + Rolipram 1 mg/kg, Group 4; OIR + Rolipram 3 mg/kg, Group 5; OIR + Rolipram 5 mg/kg. Rolipram was administered intraperitoneally to the rats in groups 3-4 and 5 at determined doses 30 minutes before reperfusion. From ovary tissue; Tumor necrosis factor-a (TNF-α), Cyclic adenosine monophosphate (cAMP), Nuclear factor kappa (NF-κB), Interleukin-6 (IL-6), Phosphodiesterase 4D (PDE4D), Mitogen-activated protein kinase (MAPK) and AQP5 levels were measured by ELISA. We also measured the level of AQP5 in ovary tissue by real-time reverse-transcription polymerase chain reaction (RT-PCR). In the OIR groups; TNF-α, NF-κB, IL-6, MAPK inflammatory levels increased, and cAMP and AQP5 levels decreased, which improved with the administration of rolipram doses. Also histopathological results showed damaged ovarian tissue after OIR, while rolipram administration decrased tissue damage in a dose dependent manner. We propose that the protective effect of PDE4 inhibition in OIR may be regulated by AQP5 and its potential cell signaling pathway and may be a new target in OIR therapy. However, clinical studies are needed to appraise these data in humans.

Mechanisms of adverse mammary effect induced by olanzapine and therapeutic interventions in rat model.

BackgroundOlanzapine antagonizes dopamine receptors and is prescribed to treat multiple psychiatric conditions. The main side effect of concern for olanzapine is weight gain and metabolic syndrome. Olanzapine induces hyperprolactinemia, however its effect on the mammary gland is poorly documented. MethodsRats received olanzapine by gavage or in drinking water at 1, 3, and 6 mg/kg/day for 5–40 days or 100 days, with and without coadministration of bromocriptine or aripiprazole and using once daily or continuous administration strategies. Histomorphology of the mammary gland, concentrations of prolactin, estradiol, progesterone, and olanzapine in serum, mammary gland and adipose tissue, and mRNA and protein expressions of prolactin receptors were analyzed. ResultsIn adult and prepubescent female rats and male rats, olanzapine induced significant development of mammary glands in dose- and time-dependent manners, with histopathological hyperplasia of mammary ducts and alveoli with lumen dilation and secretion, marked increase of mammary prolactin receptor expression, a marker of breast tissue, and with mild increase of circulating prolactin. This side effect can be reversed after medication withdrawal, but long-term olanzapine treatment for 100 days implicated tumorigenic potentials indicated by usual ductal epithelial hyperplasia. Olanzapine induced mammary development was prevented with the coaddition of the dopamine agonist bromocriptine or partial agonist aripiprazole, or by continuous administration of medication instead of a once daily regimen. ConclusionsThese results shed light on the previously overlooked effect of olanzapine on mammary development and present experimental evidence to support current clinical management strategies of antipsychotic induced side effects in the breast.

The Effects of Vitamin C on Histological Changes Induced by Acrylamide on Rat Ovary

Background and Aims: Acrylamide (ACR) adverse effects have been expressed in various tissues. Vitamin C protects the tissue from oxidative damage. The goal of this study was to examine the protective effects of vitamin C on histopathological changes induced by ACR on rat ovaries. Materials and Methods: In this experimental study, 28 adult female Wistar rats were used. The animals (n=7) were divided into 4 groups (1) Control group, (2) ACR (10 mg/kg) group, (3) vitamin C (200 mg/kg), (4) ACR [10 mg/kg) + vitamin C (200 mg/kg) daily for 35 days. After the last oral dose, the ovaries were removed placed in the tissue processor, and molded. To determine the volume of the ovary and the number of follicles, we used the Cavalieri principle and the physical dissector, respectively. Results: The results showed ACR increased the volume of the ovary (p ≤ 0.05), the volume of the medulla (p ≤ 0.01), and the decrease in the volume of the cortex (p ≤ 0.01) in comparison with the control group. These parameters were improved in the ACR + vitamin C group. The total number of primordial, primary, secondary, and graafian follicles showed a significant reduction in the ACR group compared to the other groups. The total number of follicles was increased in the ACR + vitamin C group. Conclusion: Based on this study, we concluded that vitamin C can improve histopathological changes of the ovary in ACR-exposed rats

Adolescent alcohol exposure modifies adult anxiety-like behavior and amygdala sensitivity to alcohol in rats: Increased c-Fos activity and sex-dependent microRNA-182 expression

Adolescent binge alcohol drinking is a serious health concern contributing to adult alcohol abuse often associated with anxiety disorders. We have used adolescent intermittent ethanol (AIE) administration as a model of binge drinking in rats in order to explore its long-term effect on the basolateral amygdala (BLA) responsiveness to alcohol and anxiety-like behavior. AIE increased the number of BLA c-Fos positive cells in adult Wistar rats and anxiety-like behavior assessed by the open field test (OFT). Additionally, in adult female rats receiving AIE BLA over expression of miR-182 was found. Therefore, our results indicate that alcohol consumption during adolescence can lead to enduring changes in anxiety-like behavior and BLA susceptibility to alcohol that may be mediated by sex-dependent epigenetic changes. These results contribute to understanding the mechanisms involved in the development of alcohol use disorders (AUD) and anxiety-related disorders.

Sex differences in heart rate variability measures that predict alcohol drinking in rats.

Problem alcohol drinking continues to be a substantial cost and burden. In addition, alcohol consumption in women has increased in recent decades, and women can have greater alcohol problems and comorbidities. Thus, there is a significant need for novel therapeutics to enhance sex-specific, individualized treatment. Heart rate (HR) and HR variability (HRV) are of broad interest because they may be both biomarkers for and drivers of pathological states. HRV reflects the dynamic balance between sympathetic (SNS, 'fight or flight') and parasympathetic (PNS, 'rest and digest') systems. Evidence from human studies suggest PNS predominance in women and SNS in men during autonomic regulation, indicating the possibility of sex differences in risk factors and physiological drivers of problem drinking. To better understand the association between HRV sex differences and alcohol drinking, we examined whether alcohol consumption levels correlated with time domain HRV measures (SDNN and rMSSD) at baseline, at alcohol drinking onset, and across 10min of drinking, in adult female and male Wistar rats. In particular, we compared both HRV and HR measures under alcohol-only and compulsion-like conditions (alcohol + 10mg/L quinine), because compulsion can often be a significant barrier to treatment of alcohol misuse. Importantly, previous work supports the possibility that different HRV measures could be interpreted to reflect PNS versus SNS influences. Here, we show that females with higher putative PNS indicators at baseline and at drinking onset had greater alcohol consumption. In contrast, male intake levels related to increased potential SNS measures at drinking onset. Once alcohol was consumed, HR predicted intake level in females, perhaps a pharmacological effect of alcohol. However, HRV changes were greater during compulsion-like intake versus alcohol-only, suggesting HRV changes (reduced SNS in females, reduced PNS and increased HR in males) specifically related to aversion-resistant intake. We find novel and likely clinically relevant autonomic differences associated with biological sex and alcohol drinking, suggesting that different autonomic mechanisms may promote differing aspects of female and male alcohol consumption.

Characterizing Metabolic Heterogeneity of Hepatocellular Carcinoma with Hyperpolarized 13C Pyruvate MRI and Mass Spectrometry.

Purpose To characterize the metabolomic profiles of two hepatocellular carcinoma (HCC) rat models, track evolution of these profiles to a stimulated tumor state, and assess their effect on lactate flux with hyperpolarized (HP) carbon 13 (13C) MRI. Materials and Methods Forty-three female adult Fischer rats were implanted with N1S1 or McA-RH7777 HCC tumors. In vivo lactate-to-pyruvate ratio (LPR) was measured with HP 13C MRI at 9.4 T. Ex vivo mass spectrometry was used to measure intratumoral metabolites, and Ki67 labeling was used to quantify proliferation. Tumors were first compared with three normal liver controls. The tumors were then compared with stimulated variants via off-target hepatic thermal ablation treatment. All comparisons were made using the Mann-Whitney test. Results HP 13C pyruvate MRI showed greater LPR in N1S1 tumors compared with normal liver (mean [SD], 0.564 ± 0.194 vs 0.311 ± 0.057; P < .001 [n = 9]), but not for McA-RH7777 (P = .44 [n = 8]). Mass spectrometry confirmed that the glycolysis pathway was increased in N1S1 tumors and decreased in McA-RH7777 tumors. The pentose phosphate pathway was also decreased only in McA-RH7777 tumors. Increased proliferation in stimulated N1S1 tumors corresponded to a net increase in LPR (six stimulated vs six nonstimulated, 0.269 ± 0.148 vs 0.027 ± 0.08; P = .009), but not in McA-RH7777 (eight stimulated vs six nonstimulated, P = .13), despite increased proliferation and metastases. Mass spectrometry demonstrated relatively increased lactate production with stimulation in N1S1 tumors only. Conclusion Two HCC subtypes showed divergent glycolytic dependency at baseline and during transformation to a high proliferation state. This metabolic heterogeneity in HCC should be considered with use of HP 13C MRI for diagnosis and tracking. Keywords: Molecular Imaging-Probe Development, Liver, Abdomen/GI, Oncology, Hepatocellular Carcinoma © RSNA, 2024 See also commentary by Ohliger in this issue.

Detrusor Overactivity After Partial Bladder Outlet Obstruction Is Associated With High Urinary Adenosine Triphosphate Levels in Female Wistar Rats.

Bladder outlet obstruction (BOO) commonly causes detrusor overactivity (DO). In this study, a post hoc analysis of previous obtained data, we investigate if DO occurring in initial phases of BOO is associated with changes in urinary adenosine triphosphate (ATP) levels. Adult female Wistar rats were submitted to partial BOO (pBOO) or to sham obstruction. Cystometry was performed at 3 or 15 days after pBOO and saline voided was collected for ATP determination. Normality was tested using Shapiro-Wilk test. The mean frequency of voiding contractions (VCs) of the sham-operated animals at 15 days after surgery, plus or minus 3 standard deviations, was used to represent the normal range. Statistical analyses were performed using the chi-square and Mann-Whitney tests. DO was indicated by a VC frequency greater than or equal to 0.9 VCs/min. DO was observed in 63% of animals at 3 days and in 33% at 15 days following pBOO. ATP levels were significantly higher in rats with DO compared to those without DO. The DO phenotype, occurring in the initial phases of BOO, is associated with comparatively high urinary ATP levels.

The Impact of administration of Annona muricata leaf on estrogen and progesterone functions following mercury-induced toxicity in adult female Wistar rats

Environmental toxicants have been linked to female reproductive dysfunction resulting from oxidative stress. The study assesses the impact of ethanolic leaf extract of Annona muricata (EAM) on ovarian and uterine function following mercury-induced toxicity in female Wistar rats. The study involved 40 female Wistar rats, each weighing 114–156g, divided into eight groups of five animals each. Group A received feed and water only; group B received 500 mg/kg of EAM only; and group C received 25 mg/kg of mercury chloride (HgCl2). Groups D and E received 100 mg/kg and 500 mg/kg of EAM for 4 weeks and were treated with 25 mg/kg of HgCl2, respectively. Group F received 500 mg/kg of EAM for 4 weeks and treated immediately with co-administrstion of 25 mg/kg of HgCl2 and 500 mg/kg of EAM for 4 weeks. Groups G and H received 25 mg/kg of HgCl2 and received 100 mg/kg and 500 mg/kg of EAM for 4 weeks, respectively. Progesterone amd Estrogen levels were measured at the end of the administration. The data was analysed using SPSS version 25, with inferential statistics performed, and significant values were set at p≤0.05. Administration of mercury resulted in a decreased level of estrogen, and progesterone. EAM treatments resulted in statistically significant increased levels of progesteron in groups E, F, G and H; group D also showed an increase, though not statistically significant. Estrogen levels were increased in groups F, G and H, but groups D and E showed a decrease in estrogen levels, though not statistically significant. The study reveals that EAM enhances female reproductive hormonal levels and may turn out into a potential capable of reversing or preventing female infertility linked to mercury chloride toxicity.