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See the retraction notice BIO Web of Conferences 116 , 00001 (2024), https://doi.org/10.1051/bioconf/202411600001

Light regulates numerous physiological functions including secretion of different hormones. Our aim was to determine morphological and functional changes of the pituitary growth hormone (GH) and prolactin (PRL) producing cells in female rats exposed to constant light regime from the peripubertal to adult period of life. Starting from the thirtieth postnatal day, female Wistar rats were exposed to constant light (600 lx) for the following 95 days. Controls were maintained under the regular laboratory lighting conditions. The GH and PRL cells were immunohistochemically visualized. Changes in cell volumes and volume densities were evaluated by stereology. Concentrations of PRL and GH in circulation were also determined. We detected significant decrease of the GH cell volume and volume density, followed by reduced the GH blood concentration in comparison to the controls. In contrast, PRL cells were larger in size and their volume density was significantly increased when compared to the controls. Accordingly, PRL concentration was elevated. It can be concluded that exposure of female rats to constant light regime, from peripubertal to adult period of life, causes inhibition of the pituitary GH and stimulation of PRL cells.

Gonadotropins, including human chorionic gonadotropin (hCG), are used to induce ovulation, but they have a number of side effects, including ovarian hyperstimulation syndrome (OHSS). A possible alternative is allosteric luteinizing hormone (LH)/hCG receptor agonists, including the compound TP4/2 we developed, which remains active when administered orally. The aim was to study the effectiveness of TP4/2 (orally, 40 mg/kg) as an ovulation inducer in FSH-stimulated immature female rats, compared with hCG (s.c., 15 IU/rat). TP4/2 stimulated progesterone production and corpus luteum formation; time-dependently increased the ovarian expression of steroidogenic genes (Star, Cyp11a1, Cyp17a1) and genes involved in ovulation regulation (Adamts-1, Cox-2, Egr-1, Mt-1); and increased the content of metalloproteinase ADAMTS-1 in the ovaries. These effects were similar to those of hCG, although in some cases they were less pronounced. TP4/2, in contrast to hCG, maintained normal LH levels and increased the ovarian expression of the LH/hCG receptor gene, indicating preservation of ovarian sensitivity to LH, and did not cause a sustained increase in expression of vascular endothelial growth factor-A involved in OHSS. Thus, TP4/2 is an effective ovulation inducer that, unlike hCG, has a lower risk of OHSS and ovarian LH resistance due to its moderate stimulating effect on steroidogenesis.

Breast cancer is one of the most common and well-known types of cancer among women worldwide and is the most frequent neoplasm in intact female dogs. Female dogs are considered attractive models or studying spontaneous breast cancer, whereas female rats are currently the most widely used animal models for breast cancer research in the laboratory context. Both female dogs and female rats have contributed to the advancement of scientific knowledge in this field, and, in a “One Health” approach, they have allowed broad understanding of specific biopathological pathways, influence of environmental factors and screening/discovery of candidate therapies. This review aims to clearly showcase the similarities and differences among woman, female dog and female rat concerning to anatomical, physiological and histological features of the mammary gland and breast/mammary cancer epidemiology, in order to better portray breast tumorigenesis, and to ensure appropriate conclusions and extrapolation of results among species. We also discuss the major aspects that stand out in these species. The mammary glands of female dogs and women share structural similarities, especially with respect to the lactiferous ducts and lymphatic drainage. In contrast, female rats have only one lactiferous duct per nipple. A comprehensive comparison between humans and dogs is given a special focus, as these species share several aspects in terms of breast/mammary cancer epidemiology, such as age of onset, hormonal etiology, risk factors, and the clinical course of the disease. Holistically, it is clear that each species has advantages and limitations that researchers must consider during the development of experimental designs and data analysis.

The vascular 5-HT sympatho-modulation may involve inhibitory or potentiating pathways: nitric oxide (NO), endothelium-dependent hyperpolarization (EDH)-K+ channels, prostanoids, angiotensin II (Ang-II), or endothelin. Compared to males, female rats show differences in the serotonergic sympatho-regulation; therefore, we aimed to study the involvement of indirect pathways via 5-HT1D-mediated inhibition and 5-HT2A/3-mediated potentiation of vascular noradrenergic neurotransmission in females. An i.v. bolus of different inhibitors/blockers of modulators/mediators (NO, K+ channels, prostanoids, Ang-II, or endothelin) was administered prior to the infusion of the agonists, L-694,247 (5-HT1D), TCB-2 (5-HT2A), or 1-PBG (5-HT3), in female pithed rats. In these conditions, the vascular sympathetic outflow was electrically stimulated to assess the vasopressor responses. The L-694,247 vascular sympatho-inhibition was abolished by a non-selective K+ channel blocker, tetraethylammonium. The 1-PBG sympatho-excitatory vascular effect was not modified by any of the inhibitors tested, whereas TCB-2 sympatho-potentiation was blocked solely by losartan (Ang-II type 1 receptor antagonist). Moreover, Ang-II levels were increased after TCB-2 infusion in females. The EDH pathway mediates the 5-HT1D-induced sympatho-inhibition, while the 5-HT2A-evoked sympatho-excitatory effect is associated with Ang-II. In contrast, the 5-HT3 sympatho-potentiation does not involve any indirect pathway. These findings advance current understanding of the complex interactions between 5-HT and vascular homeostasis in female rats.

Delta-9-tetrahydrocannabinol (THC) is a psychoactive element of Cannabis sativa and affects the human cannabinoid system through its receptors, CB1R and CB2R. CB1R was found in several brain areas, including the hippocampal formation (HF), and it is responsible for most THC side effects. We investigated THC’s effects in the HF of female Wistar rats to assess changes in its neurotransmission. Female Wister rats (n = 20) were gonadectomized under anesthesia at 8 weeks old. Afterwards, they received estradiol benzoate (EB) and/or THC. Immunohistochemistry was performed to assess the expression of the cholinergic receptor alpha 7 subunit (CHRNA7), the vesicular acetylcholine transporter (VAChT), the vesicular glutamate transporter (VGLUT), the gamma-aminobutyric acid type A receptor (GABRA), the CB1 receptor, and estradiol receptor alpha (EBα). In the HF, the expression of CHRNA7 was increased by EB and by THC in the Oil groups but decreased by THC in the EB groups. The same is true for VGLUT expression in the DG and hilum and for GABRA expression in the hilum. The expression of VAChT and CB1 is reduced by EB, while the concomitant administration of THC increases it. GAD expression is reduced by EB administration in CA1, CA3, and DG. Our results may help with decision-making regarding the prescription of low doses of THC as a therapeutical approach.

Background/Objectives: Diatomaceous earth (DE), a natural substance rich in amorphous silica and recognized as a food additive, is gaining attention as a dietary silicon supplement. However, its bioavailability and impact on lipid digestion and absorption remain poorly characterized. This study aimed to investigate silicon bioavailability after short-term DE supplementation and its effects on postprandial glycemia and triglyceridemia, the expression of lipid metabolism-related proteins, and the modulation of the intestinal mucosal barrier. Methods: Female Wistar rats received daily oral supplementation of DE (equivalent to 2 or 4 mg silicon/kg body weight) for one week. Silicon digestibility, excretion, and hepatic accumulation were quantified. Postprandial glycemia and triglyceridemia were monitored. Lipid profile was analyzed by HPSEC in gastric and intestinal contents. Jejunal morphology and mucin-secreting cells were assessed histologically. Lipid metabolism markers were evaluated by immunohistochemistry and Western blot in both intestinal and hepatic tissues. Results: DE supplementation enhanced silicon absorption and increased hepatic levels. Fecal output and moisture content were also elevated, especially at the higher dose. DE significantly reduced postprandial triglyceridemia and consequently increased luminal triglyceride retention. These changes were associated with decreased jejunal levels of IFABP, ACAT2, and MTP, as well as reduced hepatic levels of MTP and LDLr, alongside increased levels of ABCG5/G8 and LXRα/β, indicating a partial blockage of lipid absorption and enhanced cholesterol efflux. The effects on the intestinal barrier were evidenced by villi shortening and an increase in mucin-producing cells. Conclusion: Food-grade DE is a bioavailable source of silicon with hypolipidemic potential, mainly by reducing intestinal lipid absorption. This is supported by lower postprandial triglycerides, increased luminal lipid retention, and decreased expression of lipid transport proteins. The study in healthy female rats underscores the importance of sex-specific responses and supports DE as a dietary strategy to improve lipid metabolism.

Orexins (OX) and their receptors (OXR) modulate feeding, arousal, stress, and drug abuse. Neural systems that motivate and reinforce drug abuse may also underlie compulsive food seeking and intake. Therefore, the effects of GSK1059865 (5-bromo-N-[(2S,5S)-1-(3-fluoro-2-methoxybenzoyl)-5-methylpiperidin-2-yl]methyl-pyridin-2-amine), a selective OX(1)R antagonist, JNJ-10397049 (N-(2,4-dibromophenyl)-N'-[(4S,5S)-2,2-dimethyl-4-phenyl-1,3-dioxan-5-yl]urea), a selective OX(2)R antagonist, and SB-649868 (N-[((2S)-1-{[5-(4-fluorophenyl)-2-methyl-1,3-thiazol-4-yl]carbonyl}-2-piperidinyl)methyl]-1-benzofuran-4-carboxamide), a dual OX(1)/OX(2)R antagonist were evaluated in a binge eating (BE) model in female rats. BE of highly palatable food (HPF) was evoked by three cycles of food restriction followed by stress, elicited by exposing rats to HPF, but preventing them from having access to it for 15 min. Pharmacokinetic assessments of all compounds were obtained under the same experimental conditions used for the behavioral experiments. Topiramate was used as the reference compound as it selectively blocks BE in rats and humans. Dose-related thresholds for sleep-inducing effects of the OXR antagonists were measured using polysomnography in parallel experiments. SB-649868 and GSK1059865, but not JNJ-10397049, selectively reduced BE for HPF without affecting standard food pellet intake, at doses that did not induce sleep. These results indicate, for the first time, a major role of OX(1)R mechanisms in BE, suggesting that selective antagonism at OX(1)R could represent a novel pharmacological treatment for BE and possibly other eating disorders with a compulsive component.

Rationale Social isolation of rats immediately after weaning is thought to represent an animal model of anxiety-like disorders. Socially isolated virgin females showed a significant decrease in allopregnanolone levels, associated with increased anxiety-related behavior compared with group-housed rats. Objectives The present study investigates whether post-weaning social isolation affects maternal behavior and assesses neuroactive steroid levels in adult female rats during pregnancy and postpartum. Results Socially isolated dams displayed a reduction in the frequency of arched back nursing (ABN) behavior compared to group-housed dams. In addition, both total and active nursing were lower in socially isolated dams compared to group-housed dams. Compared to virgin females, pregnancy increases allopregnanolone levels in group-housed as well as isolated dams and such increase was greater in the latter group. Compared to pregnancy levels, allopregnanolone levels decreased after delivery and this decrease was more pronounced in isolated than group-housed dams. Moreover, the fluctuations in plasma corticosterone levels that occur in late pregnancy and during lactation follow a different pattern in socially isolated vs. group-housed rats. Conclusions The present results show that social isolation in female rats decreases maternal behavior; this effect is associated with lower allopregnanolone concentrations at postpartum, which may account, at least in part, for the poor maternal care observed in socially isolated dams. In support of this conclusion is the finding that finasteride-treated dams, which display a decrease in plasma allopregnanolone levels, also showed a marked reduction in maternal care, suggesting that allopregnanolone may contribute to the quality of maternal care.

Glucagon-like peptide-1 (GLP-1) analogs represent a new class of weight-loss medication, which has recently exponentially grown in popularity. GLP-1 is produced in the intestinal L cells in response to macronutrient intake, but it is also produced in the brain in a subset of neurons in the nucleus of the solitary tract (NTS). Exogenously-delivered GLP-1 analogs reduce food intake and food-motivated behavior in male and female rats, with some sex divergence of these effects in specific brain sites. These analogs potentially target GLP-1 receptors endogenously supplied by the gut and brain-produced GLP-1. The function of the NTS GLP-1-producing neurons [ Gcg neurons] is still relatively unknown in rats. Moreover, even less is understood about the function of these neurons in females. We have recently developed a transgenic rat that expresses Cre under the Gcg promoter. Here, we interrogate this new animal model with optogenetics and chemogenetics to determine whether activation of the NTS GLP-1 neurons affects ingestive and motivated behavior in male and female rats. Optogenetic activation of the NTS Gcg neurons robustly reduced chow intake in both male and female rats. Interestingly, motivated behavior for a sucrose reward was reduced exclusively in females. To ensure that this unexpected sex difference was not activation method-specific, we next virally introduced excitatory DREADD receptors into the Gcg neurons and investigated the effect of chemogenetic activation of these neurons on ingestive and motivated behavior. Even upon chemogenetic activation, female rats reduced their motivation to obtain the sucrose reward, yet no effect on this behavior was observed in males. Our results show that activation of hindbrain Gcg neurons is sufficient to reduce food intake in both sexes. In females, but not males, Gcg neuron activation alone is also sufficient to reduce motivated behavior for sucrose. Thus, there is a sex difference in the ability of GLP-1-producing neuron activation to control motivated behavior for food.