Oxytocin Research Articles

Titi monkey father-daughter bond-related behaviors explain stress response variability

Social interactions regulate our behavior and physiology, and strong social bonds can buffer us from stress. Coppery titi monkeys (Plecturocebus cupreus) are socially monogamous South American monkeys that display strong social bonds. Infants form selective bonds with their fathers, making them ideal for studying father-daughter bonds. We established a method for quantifying variability in expression of bond-related behaviors in females (n = 12), and the present study is the second to use this method for explaining titi monkey responses to behavioral tests. We also investigated how manipulations of oxytocin (OT) and vasopressin (AVP) influenced juvenile behavior and physiology. Subjects received acute intranasal treatments of saline, low/medium/high OT, low/high AVP, or OT receptor antagonist (OTA) prior to an acute social separation. General linear mixed-effects model results revealed fathers were significant behavioral and physiological stress buffers for their daughters, as evidenced by fewer distress vocalizations (p < 0.001), less locomotion (p < 0.001), and lower plasma cortisol (p < 0.001) in a social separation paradigm. Females vocalized less if they exhibited greater expression of bond-related behaviors with their fathers as infants (p = 0.01), and this stress-buffering effect remained even when the daughter was separated from the father (p = 0.001). While treatments did not alter behaviors, OTA treatment caused the largest rise in plasma cortisol (p < 0.001), suggesting blockade of OT receptors can inhibit fathers’ stress-buffering effects. Remarkably, females with greater expression of father-daughter bond-related behaviors exhibited an overall reduced physiological separation distress response (p = 0.04). Findings from the present study advance current knowledge of the neurobiological mechanisms foundational to female bonds and help inform how social disruptions may differently impact individuals based on expression of bond-related behaviors.

Better safe than sorry: Oxytocin shifts the regulatory focus

Oxytocin (OT) is known to play a major role in social cognition and behavior. In this study, we aimed to investigate whether OT also affects the motivational system, specifically, the regulatory focus. Because OT weakens the self- and promotes the other-bias, we hypothesized that OT would decrease promotion focus and increase prevention focus. To test this, we conducted two experiments. In each, male participants intranasally administered OT or a placebo and assessed their regulatory focus using validated paradigms. Results revealed that OT led to an increase of prevention focus (Studies 1 and 2) and a slight but non-significant decrease of promotion focus (Study 2). Thus, participants under OT (vs. placebo) saw potential losses as more important, while they tended to devaluate potential gains. This was unrelated to the perceived likelihood of success. These findings indicate that OT might provide adaption to the social environment by pursuing a vigilant motivational strategy.

Oxytocin Receptor Expression in Hair Follicle Stem Cells: A Promising Model for Biological and Therapeutic Discovery in Neuropsychiatric Disorders.

The intricate nature of the human brain and the limitations of existing model systems to study molecular and cellular causes of neuropsychiatric disorders represent a major challenge for basic research. The promising progress in patient-derived stem cell technology and in our knowledge on the role of the brain oxytocin (OXT) system in health and disease offer new possibilities in that direction. In this study, the rat hair follicle stem cells (HFSCs) were isolated and expanded in vitro. The expression of oxytocin receptors (OXTR) was evaluated in these cells. The cellular viability was assessed 12 h post stimulation with OXT. The activation of OXTR-coupled intracellular signaling cascades, following OXT treatment was determined. Also, the influence of OXT on neurite outgrowth and cytoskeletal rearrangement were defined. The assessment of OXTR protein expression revealed this receptor is expressed abundantly in HFSCs. As evidenced by the cell viability assay, no adverse or cytotoxic effects were detected following 12 h treatment with different concentrations of OXT. Moreover, OXTR stimulation by OXT resulted in ERK1/2, CREB, and eEF2 activation, neurite length alterations, and cytoskeletal rearrangements that reveal the functionality of this receptor in HFSCs. Here, we introduced the rat HFSCs as an easy-to-obtain stem cell model that express functional OXTR. This cell-based model can contribute to our understanding of the progression and treatment of neuropsychiatric disorders with oxytocinergic system deficiency.

Effect of intranasal oxytocin on palatable food consumption and c-Fos immunoreactivity in relevant brain areas in rats

Peripheral and central injections of oxytocin (OT) in laboratory animals decrease eating for energy and palatability, but the hypophagic response is dependent on the administration route. Human studies rely on intranasal (IN) administration of the peptide, the route underutilized in OT animal feeding studies thus far. Therefore, we examined the effect of IN OT on various aspects of food consumption in rats: (a) overnight deprivation-induced standard chow intake, (b) episodic (2-h) consumption of calorie-dense and palatable high-fat high-sugar (HFHS) chow, (c) 2-h episodic intake of palatable and calorie-dilute sucrose and Intralipid solutions, and (d) 2-h sucrose solution intake in rats habituated to ingesting this solution daily for several weeks. Finally, we assessed c-Fos changes in response to the acute IN OT administration in rats habituated to daily sugar consumption. We found that IN 20μg OT decreased deprivation-induced intake of standard chow and HFHS chow in nondeprived rats without affecting water consumption. IN OT also reduced 2-hour episodic fluid consumption of sucrose, but not Intralipid. In the habitual sugar consumption paradigm, acute IN OT diminished sucrose solution intake in animals accustomed to the 2-hour/day sucrose meal regimen. In rats habitually consuming sucrose, IN OT altered c-Fos immunoreactivity in brain areas related to energy homeostasis and reward, including the central nucleus of the amygdala, the hypothalamic paraventricular and the arcuate nuclei. We conclude that IN OT is an effective appetite suppressant for carbohydrate/sugar diets in rats and its effects involve feeding-related brain circuits.

Engineered macrophage-biomimetic versatile nanoantidotes for inflammation-targeted therapy against Alzheimer's disease by neurotoxin neutralization and immune recognition suppression.

Immune recognition of excessive neurotoxins by microglia is a trigger for the onset of neuroinflammation in the brain, leading to neurodegeneration in Alzheimer's disease (AD). Blocking active recognition of microglia while removing neurotoxins holds promise for fundamentally alleviating neurotoxin-induced immune responses, but is very challenging. Herein, an engineered macrophage-biomimetic versatile nanoantidote (OT-Lipo@M) is developed for inflammation-targeted therapy against AD by neurotoxin neutralization and immune recognition suppression. Coating macrophage membranes can not only endow OT-Lipo@M with anti-phagocytic and inflammation-tropism capabilities to target inflammatory lesions in AD brain, but also efficiently reduce neurotoxin levels to prevent them from activating microglia. The loaded oxytocin (OT) can be slowly released to downregulate the expression of immune recognition site Toll-like receptor 4 (TLR4) on microglia, inhibiting TLR4-mediated pro-inflammatory signalling cascade. Benefiting from this two-pronged immunosuppressive strategy, OT-Lipo@M exhibits outstanding therapeutic effects on ameliorating cognitive deficits, inhibiting neuronal apoptosis, and enhancing synaptic plasticity in AD mice, accompanied by the delayed hippocampal atrophy and brain microstructural disruption by in vivo 9.4T MR imaging. This work provides new insights into potential AD therapeutics targeting microglia-mediated neuroinflammation at the source.

Fruit Extract of Oil Palm (&lt;i&gt;Elaeis Guineensis&lt;/i&gt; (Jacq.)) Inhibits Uterine Contractility in &lt;i&gt;Ex-Vivo&lt;/i&gt; Mouse Models

Background: Different parts of Elaeis guineensis (EG) plants are used ethno-medicinally for treating numerous illnesses including abdominal contraction.&#x0D; Objectives: Thus, this study evaluated the inhibitory potential of the fruit-extract of EG on the uterine contractility in ex-vivo mouse models.&#x0D; Material and Methods: The effect of EG extract on spontaneous uterine contractions, oxytocin (OT)-induced uterine contractions, high potassium chloride induced uterine contractions and oxytocin-induced calcium free contraction were evaluated in adult non-pregnant female albino mice.&#x0D; Results: EG in a concentration dependent mode diminished spontaneous uterine contractions, while amplitude and frequency of contractions were inhibited significantly, but the frequency of contraction was at the highest concentration of EG. EG also produced a significant inhibition of the frequency of OT-induced contraction in calciumfree media.&#x0D; Conclusion: The aqueous fruit extracts of EG inhibited uterine contraction in the uterus through inhibition of intracellular calcium stores.

The Interplay of Oxytocin and Attachment in Schizophrenic Patients: An fMRI Study.

Attachment theory offers an important framework for understanding interpersonal interaction experiences. In the present study, we examined the neural correlates of attachment patterns and oxytocin in schizophrenic patients (SZP) compared to healthy controls (HC) using fMRI. We assumed that male SZP shows a higher proportion of insecure attachment and an altered level of oxytocin compared to HC. On a neural level, we hypothesized that SZP shows increased neural activation in memory and self-related brain regions during the activation of the attachment system compared to HC. We used an event-related design for the fMRI study based on stimuli that were derived from the Adult Attachment Projective Picture System to examine attachment representations and their neural and hormonal correlates in 20 male schizophrenic patients compared to 20 male healthy controls. A higher proportion of insecure attachment in schizophrenic patients compared to HC could be confirmed. In line with our hypothesis, Oxytocin (OXT) levels in SZP were significantly lower than in HC. We found increasing brain activations in SZP when confronted with personal relevant sentences before attachment relevant pictures in the precuneus, TPJ, insula, and frontal areas compared to HC. Moreover, we found positive correlations between OXT and bilateral dlPFC, precuneus, and left ACC in SZP only. Despite the small sample sizes, the patients' response might be considered as a mode of dysregulation when confronted with this kind of personalized attachment-related material. In the patient group, we found positive correlations between OXT and three brain areas (bilateral dlPFC, precuneus, left ACC) and may conclude that OXT might modulate within this neural network in SZP.

Inflammation and mitochondrial dysfunction in affective disorders-novel understandings, novel treatments?

BackgroundMitochondria are involved in energy production, oxidative balance, cell survival/apoptosis, immune response, and inflammation. A possible role in affective disorders has fueled research on mitochondrial targets for novel treatments. MethodsA systematic review of the literature was conducted, in Science Direct, Scopus and PubMed databases, from inception to 12th September 2022. Key words used were mitochondria AND/OR inflammation AND affective OR bipolar OR depression AND therapy OR treatment OR intervention. ResultsTwenty-one studies were included in the analysis. Animal studies (n=16) have shown positive results for Nucleus Accumbens Deep Brain Stimulation (NAc DBS), Near-Infrared Photobiomodulation (NIR-PBM), exercise, 48-hour fasting, and fluoxetine, Li, valproate, BI-11A7 Bid inhibitor, methylene blue (MB), AC-5216, atractylenolide-III (ALT-III), ONO-2952, oxytocin (OT), tocopherol-a, Coenzyme Q10 (CoQ10). Human studies (n=5) have tested adjunctive therapies, with NAC plus antioxidant combination therapy, triacetyl-uridine (TAU), cytidine add-on, and andacetyl-l-carnitine and a-lipoic acid combination, with positive (TAU), negative, or difficult-to-interpret results. LimitationsThe search was conducted on three databases only, and only articles written in English were included. Unpublished articles or research with negative results may have been missed. ConclusionMitochondria-targeting interventions are promising novel treatments for depression and bipolar disorder.

Electroacupuncture Ameliorates Hypothalamic‒Pituitary‒Adrenal Axis Dysfunction Induced by Surgical Trauma in Mice Through the Hypothalamic Oxytocin System.

Electroacupuncture (EA) can effectively reduce surgical stress reactions and promote postoperative recovery, but the mechanisms remain unclear. The present study aims to examine the effects of EA on the hyperactivity of the hypothalamic‒pituitary‒adrenal (HPA) axis and investigate its potential mechanisms. Male C57BL/6 mice were subjected to partial hepatectomy (HT). The results showed that HT increased the concentrations of corticotrophin-releasing hormone (CRH), corticosterone (CORT), and adrenocorticotropic hormone (ACTH) in the peripheral blood and upregulated the expression of CRH and glucocorticoid receptors (GR) proteins in the hypothalamus. EA treatment significantly inhibited the hyperactivity of the HPA axis by decreasing the concentration of CRH, CORT, and ACTH in peripheral blood and downregulating the expression of CRH and GR in the hypothalamus. Moreover, EA treatment reversed the HT-induced downregulation of oxytocin (OXT) and oxytocin receptor (OXTR) in the hypothalamus. Furthermore, intracerebroventricular injection of the OXTR antagonist atosiban blocked the effects of EA. Thus, our findings implied that EA mitigated surgical stress-induced HPA axis dysfunction by activating the OXT/OXTR signaling pathway.

Characterization of rat gastric myogenic contractions and modulation by oxytocin and arginine-vasopressin

BackgroundInterstitial cells of Cajal generate slow wave gastric electrical activity, initiating spontaneous muscle contractions. This becomes dysrhythmic during nausea when [Arg8]-vasopressin (AVP) is also released. In human stomach AVP increased spontaneous contraction activity and muscle tone, not neuronally-mediated contractions. Rodents cannot vomit, releasing the related hormone, oxytocin (OT) instead. We hypothesised that rat stomach would behave differently. Experimental approachSpontaneous and electrically-evoked (EFS) contractions were measured in rat forestomach and antrum circular muscle. Custom software defined spontaneous contractions by analysing eight motility parameters. ResultsThe forestomach was quiescent. Irregular antrum contractions became regular adjacent to the pylorus (1.7 ± 0.4 mN; 1.2 ± 0.1 contractions/min, n = 12). These were unaffected by tetrodotoxin (10−6 M), atropine (10−6 M) and L-NAME (3 × 10−4 M). In both regions, AVP (pEC50∼9.0) and OT (∼0.5 log10-unit less potent) caused contraction (greater in antrum), competitively antagonized by, respectively, SR49059 (pKB∼9.5) and L371257 (pKB∼9.0), reduced by tetrodotoxin but unaffected by atropine. In the antrum, AVP and OT (∼2 log10-units less potent/efficacious) regularized and increased spontaneous contraction amplitude, frequency, rates of contraction/decay. In both regions, EFS-evoked contractions, abolished by atropine/tetrodotoxin, were reduced by AVP and OT, with AVP more potent and efficacious, particularly in forestomach. ConclusionIrregular spontaneous contractions of gastric antrum suggest variable ICC-muscle coupling. AVP and less potently, OT, enhanced frequency and force of contractions via V1A and OT receptors. Compared with human, differences in contraction regularity, potency and ability of AVP/OT to affect neuronal function suggests caution when using rat stomach to model ICC functions and nauseagenic stimuli.

Effect of processing with vinegar on efficacy of Curcuma longa in treatment of dysmenorrhea in rats with syndrome of liver depression and Qi stagnation

This study compared the effects of Curcuma longa before and after processing with vinegar on the rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation to reveal the mechanism of vinegar processing in improving the role of C. longa in soothing liver and relieving pain. The rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation was established according to the Preparation of the Animal Model of Dysmenorrhea(Draft) and the chronic unpredictable stress me-thod. The changes in the body weight, organ indexes, writhing latency, writhing score, and serum levels of six liver function indicators, sex hormones, pain factors, and blood rheological indicators were measured to evaluate the efficacy of C. longa processed with vinegar or not in treating dysmenorrhea in the rats with syndrome of liver depression and qi stagnation. Compared with the model group, the C. longa group(processed with vinegar or not) showed slow weight loss, increase in writhing latency, and decrease in writhing response(P&lt;0.05). The inhibition rates on writhing in raw C. longa, vinegar-processed C. longa, and positive groups were 33.780%, 64.611%, and 62.466%, respectively. The significantly higher inhibition rate of the vinegar processing group indicated that vinegar-processed C. longa demonstrated more significant therapeutic effect. The vinegar-processed C. longa group showed lower levels of alanine aminotransferase(ALT), alkaline phosphatase(ALP), aspartate aminotransferase(AST), direct bilirubin(DBIL), and total bilirubin(TBIL) and higher level of albumin(ALB)(P&lt;0.05), which indicated that vinegar processing enhanced the therapeutic effect of C. longa on liver injury. The serum levels of estradiol(E_2) and oxytocin(OT) were lower in the vinegar-processed C. longa group(P&lt;0.05), indicating that the vinegar-processed C. longa could regulate the sex hormone levels, reduce the activity of uterine smooth muscle and contraction of uterus, and alleviate the symptoms of dysmenorrhea in rats. Moreover, the vinegar-processed C. longa group showed lower interleukin-6(IL-6) and arginine vasopressin(AVP) levels and higher beta-endorphin(β-EP) level(P&lt;0.05), which indicated that vinegar-processed C. longa regulated the levels of pain factors to exert the pain-relieving effect. Drug intervention decreased the whole blood viscosity low-cut, medium-cut and high-cut values, plasma viscosity, whole blood reduction viscosity low-cut and high-cut values, erythrocyte cumulative pressure, and equation K value of erythrocyte sedimentation rate(P&lt;0.05), and the vinegar-processed C. longa group outperformed other groups. This result indicated that vinegar processing enhanced the function of C. longa in improving the local blood rheology. C. longa processed with vinegar can enter the liver to relieve the da-mage to the heart, liver, kidney, and uterus, repair the liver function, and recover the sex hormone levels and immune function by regulating the levels of sex hormones and pain factors and improving the blood rheology. It activates the pain-relieving mechanism to relieve the pain, protect the liver, and fight inflammation, which is consistent with the theory that vinegar processing facilitates C. longa entering the liver to sooth liver and relieve pain.

Oxytocin Modulates Osteogenic Commitment in Human Adipose-Derived Stem Cells.

Human adipose-derived stem cells (hASCs) are commonly harvested in minimally invasive contexts with few ethical concerns, and exhibit self-renewal, multi-lineage differentiation, and trophic signaling that make them attractive candidates for cell therapy approaches. The identification of natural molecules that can modulate their biological properties is a challenge for many researchers. Oxytocin (OXT) is a neurohypophyseal hormone that plays a pivotal role in the regulation of mammalian behavior, and is involved in health and well-being processes. Here, we investigated the role of OXT on hASC proliferation, migratory ability, senescence, and autophagy after a treatment of 72 h; OXT did not affect hASC proliferation and migratory ability. Moreover, we observed an increase in SA-β-galactosidase activity, probably related to the promotion of the autophagic process. In addition, the effects of OXT were evaluated on the hASC differentiation ability; OXT promoted osteogenic differentiation in a dose-dependent manner, as demonstrated by Alizarin red staining and gene/protein expression analysis, while it did not affect or reduce adipogenic differentiation. We also observed an increase in the expression of autophagy marker genes at the beginning of the osteogenic process in OXT-treated hASCs, leading us to hypothesize that OXT could promote osteogenesis in hASCs by modulating the autophagic process.

(046) Signalling the Vaginal Code: A Dual Role for Oxytocin in Sexual Partner Preference and Reproduction

Abstract Introduction In female rats, paced copulation induces a neuroendocrine response that is necessary for pregnancy. Paced copulation is also a strong sexual reinforcer that results in both conditioned place preference and conditioned sexual partner preference. Although the neuropeptide oxytocin (OT) controls partner preference formation in female prairie voles, it is not known whether OT regulates sexual preference formation in female rats. Objectives The current experiments tested whether (i) OT is necessary and sufficient to induce a sexual partner preference, and (ii) OT signalling affects the reproductive effects of pacing that are necessary for both pregnancy and partner preference. These experiments also tested whether peripheral or central OT signalling regulates these behaviours by using an antagonist that enters the CNS (Cligosiban, 5mg/kg; CLG) and one that does not (L-371,257, 1mg/kg; data collection in progress). Methods In the first experiment, Long-Evans female rats (n = 14) were injected I.P. with either saline, 20μg OT, 50μg OT, CLG, L-371,257, one minute before their first 30-min sexual experience with a male rat scented with almond. Four days later, the females were given a drug-free 30-min partner preference test in an open field with two males, one scented and the other unscented. The second experiment tested whether OT signalling augments the facilitation of estrous termination that is reliably induced with stimulation of the cervix (VCS). Long-Evans females (n = 12) were injected with either saline, 50μg OT, CLG, or L371,257, 1min prior to sham stimulation or 50 distributed VCSs administered with a lubricated glass rod. Twelve hr after VCS or sham females copulated with a male to assess sexual receptivity. Results In the first experiment, females treated with both doses of OT received the scented male’s ejaculation first and more often, but they did not solicit the scented male more often than the unscented male. CLG-treated females received the unscented male’s first ejaculation preferentially and solicited the unscented male more often. In the second experiment, females treated with OT showed decreased sexual receptivity regardless of the type of stimulation, suggesting that OT mimicked the effect of VCS. In contrast, estrous termination was attenuated in females given CLG and L371,257 with VCS, suggesting that central and peripheral OT receptors play a role in activating neuroendocrine responses induced by copulation. Conclusions Taken together, these data suggest that OT signalling regulates aspects of both reproduction and sexual reward in female rats, biasing their preferences to receive ejaculations preferentially from males that are associated with paced copulation and terminating their sexual receptivity faster, thus, increasing the likelihood of pregnancy and paternity. Disclosure No.

Intraamygdaloid Oxytocin Increases Time Spent on Social Interaction in Valproate-Induced Autism Animal Model.

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder that affects about 1.5% of children worldwide. One of the core symptoms is impaired social interaction. Since proper treatment has not been found yet, an investigation of the exact pathophysiology of autism is essential. The valproate (VPA)-induced rat model can be an appropriate way to study autism. Oxytocin (OT) may amend some symptoms of ASD since it plays a key role in developing social relationships. In the present study, we investigated the effect of the intraamygdaloid OT on sham and intrauterine VPA-treated rats' social interaction using Crawley's social interaction test. Bilateral guide cannulae were implanted above the central nucleus of the amygdala (CeA), and intraamygdaloid microinjections were carried out before the test. Our results show that male Wistar rats prenatally exposed to VPA spent significantly less time on social interaction. Bilateral OT microinjection increased the time spent in the social zone; it also reached the level of sham-control animals. OT receptor antagonist blocked this effect of the OT but in itself did not significantly influence the behavior of the rats. Based on our results, we can establish that intraamygdaloid OT has significantly increased time spent on social interaction in the VPA-induced autism model, and its effect is receptor-specific.

O-245 Monitoring oxytocin release in vivo during female sexual behavior using a genetically encoded sensor

Abstract Study question To investigate if the release of oxytocin (OT) in the medial prefrontal cortex (mPFC) fluctuates during discrete phases of female sexual behavior. Summary answer Using a highly sensitive OT-specific genetically encoded sensor, we have recorded behavioral phase-specific OT release in mPFC in freely moving mice. What is known already OT has been reported to participate in the regulation of sexual behavior of both male and female mice. OT activated mPFC neurons by increasing their firing activity. Loss of function studies indicated that pharmacological or genetic ablation of OT signaling in mPFC largely disrupts female sociosexual interest in male mice. OT action is indispensable in female sociosexual behavior, however, its release dynamics have never been recorded before due to technical difficulties. We have developed a highly sensitive OT-specific G-protein-coupled receptor activation-based sensor (OT1.0), and recorded intracellular OT release in behaving mice on the millisecond time-scale. Study design, size, duration Eight C57BJ/6N mice were divided into two groups (n = 4 per group). Intracellular viral transduction with OT1.0 or OT1.0mut vectors was administrated to each group. After viral transduction, 3 weeks were waited to allow sufficient viral expression. Participants/materials, setting, methods After anesthetization, AAVs encoding hSyn-OT1.0 or hSyn-OT1.0mut were injected into the left mPFC of adult female wild-type C57BJ/6N mice; Optical fibers were implanted into the mPFC 3 weeks after AAV injection. The animal’s sexual behaviors were recorded and annotated, while a fiber photometry system was used to record fluorescence signals in the mPFC, using a 470-nm laser at 50 μW for OT1.0 or OTmut. Main results and the role of chance To investigate the dynamics of OT release in mPFC during female sexual behavior, we recorded OT1.0 fluorescence in behaving female mice using fiber photometry. In mPFC of female mice, increases in OT1.0 fluorescence were first observed during the sniffing stage (with rise and decay time constants (T1/2) of 0.4 s and 1.4 s, respectively ). After ejaculation of male mice, mPFC OT1.0 signals of the female mice increased significantly with rise and decay time constants (T1/2) of 0.5 s and 1.5 s, respectively. As a negative control, fluctuation of fluorescence was not observed during any phase of sexual behavior in mice expressing OT1.0mut, suggesting the specificity of the signals measured in mice expressing OT1.0. Limitations, reasons for caution The OT dynamics in mPCF during female sexual behaviors are only recorded in mice. Clinical trials and imaging studies are required to substantiate the therapeutic role of OT in human subjects. Wider implications of the findings This study is likely to deepen our understanding of the role of OT in modulating female sociosexual behavior, which provides more evidence suggesting OT’s potential therapeutic potential in treating sexual dysfunctions. Trial registration number not applicable

Developmental Changes in Hypothalamic and Serum Oxytocin Levels in Prenatally Normally Nourished and Undernourished Rats.

Changes in the activities of some metabolic factors have been suggested to increase the risk of conditions associated with the Developmental Origins of Health and Disease (DOHaD). We examined changes in oxytocin (OT), a metabolic factor, and OT receptor (OTR) mRNA levels throughout the developmental period in rats of intrauterine undernutrition. Pregnant rats were divided into two groups: a maternal normal nutrition (mNN) and maternal undernutrition (mUN) group. Serum OT concentrations and hypothalamic mRNA levels of OT and OTR were measured in both offspring at various postnatal stages. Both offspring showed significant increases in serum OT concentrations during the neonatal period, significant reductions around the pubertal period, and significant increases in adulthood. Hypothalamic OT mRNA expression levels gradually increased from the neonatal to pubertal period and decreased in adulthood in both offspring. In the pre-weaning period, hypothalamic OT mRNA expression levels were significantly lower in the mUN offspring than in the mNN offspring. In the mUN offspring, hypothalamic OTR mRNA expression levels transiently increased during the neonatal period, decreased around the pubertal period, and increased again in adulthood, whereas transient changes were not detected in mNN offspring. These changes could affect nutritional and metabolic regulation systems in later life and play a role in the mechanisms underlying DOHaD.

Assessment of Tissue Expression of the Oxytocin-Vasopressin Pathway in the Placenta of Women with a First-Episode Psychosis during Pregnancy.

Psychosis refers to a mental health condition characterized by a loss of touch with reality, comprising delusions, hallucinations, disorganized thought, disorganized behavior, catatonia, and negative symptoms. A first-episode psychosis (FEP) is a rare condition that can trigger adverse outcomes both for the mother and newborn. Previously, we demonstrated the existence of histopathological changes in the placenta of pregnant women who suffer an FEP in pregnancy. Altered levels of oxytocin (OXT) and vasopressin (AVP) have been detected in patients who manifested an FEP, whereas abnormal placental expression of these hormones and their receptors (OXTR and AVPR1A) has been proven in different obstetric complications. However, the precise role and expression of these components in the placenta of women after an FEP have not been studied yet. Thus, the purpose of the present study was to analyze the gene and protein expression, using RT-qPCR and immunohistochemistry (IHC), of OXT, OXTR, AVP, and AVPR1a in the placental tissue of pregnant women after an FEP in comparison to pregnant women without any health complication (HC-PW). Our results showed increased gene and protein expression of OXT, AVP, OXTR, and AVPR1A in the placental tissue of pregnant women who suffer an FEP. Therefore, our study suggests that an FEP during pregnancy may be associated with an abnormal paracrine/endocrine activity of the placenta, which can negatively affect the maternofetal wellbeing. Nevertheless, additional research is required to validate our findings and ascertain any potential implications of the observed alterations.

Oxytocin Improves Intracerebral Hemorrhage Outcomes by Suppressing Neuronal Pyroptosis and Mitochondrial Fission.

Intracerebral hemorrhage (ICH) causes severe sensorimotor dysfunction and cognitive decline which are aggravated by secondary brain injury, yet there are no effective management to alleviate these outcomes. Pyroptosis is strongly related to neuroinflammation, which plays a crucial role in the pathophysiological processes of secondary brain injury after ICH. OXT (oxytocin), as a pleiotropic neuropeptide, has multiple functions including anti-inflammation and antioxidation. This study aims to investigate the role of OXT in improving ICH outcomes and the underlying mechanisms. C57BL/6 mice were used to establish the ICH model by autologous blood injection. OXT was administered intranasally (0.2 μg/g) after ICH. Combing behavioral tests, Western blot, immunofluorescence staining, electron microscopy, and pharmacological approaches, we evaluated the effect of intranasal OXT application on neurological outcomes after ICH and explored the underlying mechanism. Endogenous OXT level was decreased, whereas OXTR (oxytocin receptor) expression was increased after ICH. OXT treatment improved the short-term and long-term neurological functions and alleviated neuronal pyroptosis and neuroinflammation. In addition, OXT reduced excessive mitochondrial fission and mitochondrial-derived oxidative stress 3 days after ICH. OXT decreased the expression of pyroptotic and proinflammatory factors including NLRP3 (NOD-like receptor protein 3), ASC (apoptosis-associated speck-like protein containing a CARD), GSDMD (gasdermin D), caspase-1, IL (interleukin)-1β, and IL-18 and increased the expression of p-PKA (phospho-protein kinase A) and p-DRP1 (S637; DRP1 [dynamin-related protein 1] phosphorylation at Ser637). OXT-induced neuroprotective effects were blocked by either OXTR inhibitor or PKA inhibitor. Intranasal application of OXT can ameliorate neurological deficits and alleviate neural pyroptosis, inflammation, and excessive mitochondrial fission via OXTR/p-PKA/DRP1 signaling pathway after ICH. Thus, OXT administration may be a potential therapeutic strategy to improve the prognosis of ICH.

Oxytocin administration is a potential tool for behavioral management in felids

Living in a group setting is essential for the health and wellbeing of social carnivores; however, the managed formation of captive groups of territorial animals can be challenging because of the risk of aggression, injury, and even death. Numerous laboratory and clinical studies have implicated oxytocin in the formation of social bonds. Previously, we have shown that oxytocin (OT) administration reduced social vigilance in African lions. Here, we describe a series of case reports in which OT administration was used to facilitate social bonding in both familiar and unfamiliar conspecific pairs and groups of African lions and tigers, and we provide qualitative descriptions of the study animals’ behaviors before and after treatment. We hypothesized that the repeated intranasal administration of oxytocin over a period of 6–8 weeks would facilitate (1) the bonding process during introductions of unfamiliar individuals and (2) reconciliation between paired individuals that had developed ongoing negative social relationships. Following OT treatment, positive social interactions were either observed for the first time or were restored in all seven study groups.

Serum Oxytocin Levels Decrease 12 Months Following Sleeve Gastrectomy and Are Associated with Decreases in Lean Mass.

Oxytocin (OXT), an anorexigenic hormone, is also bone anabolic. Further, OXT administration results in increases in lean mass (LM) in adults with sarcopenic obesity. We examine, for the first time, associations of OXT with body composition and bone endpoints in 25 youth 13-25 years old with severe obesity who underwent sleeve gastrectomy (SG) and 27 non-surgical controls (NS). Forty participants were female. Subjects underwent fasting blood tests for serum OXT and DXA for areal bone mineral density (aBMD) and body composition. At baseline, SG vs. NS had higher median body mass index (BMI) but did not differ for age or OXT levels. Over 12 months, SG vs. NS had greater reductions in BMI, LM, and fat mass (FM). OXT decreased in SG vs. NS 12 months post-SG. While baseline OXT predicted a 12-month BMI change in SG, decreases in OXT levels 12 months post-SG were not associated with decreases in weight or BMI. In SG, decreases in OXT were positively associated with decreases in LM but not with decreases in FM or aBMD. Loss of LM, a strong predictor of BMD, after bariatric surgery may reduce functional and muscular capacity. OXT pathways may be targeted to prevent LM loss following SG.