Application Of Oxytocin Research Articles

Oxytocin alleviates high-fat diet-induced anxiety by decreasing glutamatergic synaptic transmission in the ventral dentate gyrus in adolescent mice

A high-fat diet (HFD)-induced obesity is associated with mental disorders in adolescence. However, the mechanisms underlying these associations remain unclear. In this study, we hypothesized that synaptic remodeling occurs in the ventral hippocampus (vHP) of obese mice. To investigate this, we established a postnatal model of HFD-induced obesity in mice and observed increased body weight, elevated plasma luteinizing hormone and testosterone levels, premature puberty, and enhanced anxiety-like behavior in male subjects. We also examined the effect of HFD on the c-Fos protein expression in the ventral dentate gyrus (vDG) and explored the influence of intracerebroventricular (i.c.v) oxytocin injections on HFD-induced anxiety. Our results indicated an increase in c-Fos-positive cells in the vDG following HFD consumption. Additionally, we recorded the spontaneous synaptic activity of miniature excitatory postsynaptic currents (mEPSCs) in the vDG. Notably, HFD resulted in an elevated mEPSC frequency without affecting mEPSC amplitude. Subsequently, investigations demonstrated that i.c.v oxytocin injections reversed anxiety-like behavior induced by HFD. Moreover, the application of oxytocin in a bath solution reduced the mEPSC frequency in the vDG. These findings suggest that postnatal HFD intake induces synaptic dysfunction in the vDG, associated with the hyperactivity of vDG neurons, potentially contributing to the anxiety-like behavior in juvenile obesity.

Oxytocin Receptors on Calvarial Periosteal Innervation: Therapeutic Target for Post-Traumatic Headache?

Following a mild traumatic brain injury (mTBI), the most prevalent and profoundly debilitating occurrence is the emergence of an acute and persistent post-traumatic headache (PTH), for which there are presently no approved treatments. A crucial gap in knowledge exists regarding the consequences of an mTBI, which could serve as a foundation for the development of therapeutic approaches. The activation of trigeminal sensory nerve terminals that innervate the calvarial periosteum (CP)-a densely innervated tissue layer covering the calvarial skull-has been implicated in both migraines and PTHs. We have previously shown that trigeminal oxytocin receptors (OTRs) may provide a therapeutic target for PTHs. This study examined the expression of oxytocin receptors on trigeminal nerves innervating the periosteum and whether these receptors might serve as a therapeutic target for PTHs using a direct application of oxytocin to the periosteum in a rodent model of PTH. We used retrograde tracing and immunohistochemistry to determine if trigeminal ganglion (TG) neurons innervating the periosteum expressed OTRs and/or CGRPs. To model the impact of local inflammation that occurs following an mTBI, we applied chemical inflammatory mediators directly to the CP and assessed for changes in immediate-early gene expression as an indication of neuronal activation. We also determined whether mTBI would lead to expression changes to OTR levels. To determine whether these OTRs could be a viable therapeutic target, we assessed the impact of oxytocin injections into the CP in a mouse model of PTH-induced periorbital allodynia. The results of these experiments demonstrate the following: (1) the cell bodies of CP afferents reside in the TG and express both OTRs and CGRPs; (2) inflammatory chemical stimulation of the periosteum leads to rapid activation of TG neurons (phospho-ERK (p-ERK) expression), (3) mTBI-induced inflammation increased OTR expression compared to the sham group; and (4) administration of oxytocin into the periosteum on day 2 and day 40 blocked cutaneous allodynia for up to one hour post-administration for both acute and persistence phases in the PTH model-an effect that was preventable by the administration of an OTR antagonist. Taken together, our observations suggest that periosteal trigeminal afferents contribute to post-TBI craniofacial pain, and that periosteum tissue can be used as a potential local target for therapeutics such as oxytocin.

Body weight modulates the impact of oxytocin on chronic cold-immobilization stress response

By activating the stress system, stress modulates various physiological parameters including food intake, energy consumption, and, consequently, body weight. The role of oxytocin in the regulation of stress and obesity cannot be disregarded. Based on these findings, we aimed to investigate the effect of intranasal oxytocin on stress response in high-fat-diet (HFD)--fed and control-diet-fed rats exposed to chronic stress. Cold-immobilization stress was applied for 5 consecutive days to male Sprague-Dawley rats fed either with a control diet (n=20) or HFD (n=20) for 6 weeks. Half of the animals in each group received oxytocin. Stress response was evaluated via plasma and salivary cortisol levels as well as elevated plus maze scores. Prefrontal cortex and hypothalamic oxytocin receptor (OxtR) expression levels were identified using western blot analysis. The results showed higher stress response in HFD-fed animals than in control animals both under basal and post-stress conditions. Oxytocin application had a prominent anxiolytic effect in the control group but an insignificant effect in the HFD group. While OxtR expression levels in the prefrontal cortex did not vary according to the body weight and oxytocin application, OxtR levels in the hypothalamus were higher in the HFD- and/or oxytocin-treated animals. Our results indicated that the peripheral and central effects of oxytocin vary with body weight. Moreover, obesity masks the anxiolytic effects of oxytocin, probably by reinforcing the stress condition via central OxtRs. In conclusion, elucidating the mechanisms underlying the central effect of oxytocin is important to cope with stress and obesity.

Design and synthesis of oxytocin glycosides for the treatment of pain and substance use disorder.

Peptide drugs are a promising alternative to classical small molecule therapeutics with diverse applications, ranging from antibiotic resistant infection to prostate cancer. Oxytocin (OT) is a highly evolutionarily conserved peptide neurohormone and has been of interest for pharmaceutical use since 1909. Despite their increased safety profile relative to most small molecule drugs, peptides are poor candidates based on the pharmacokinetic (PK) properties from their peptide nature. Broad application of OT as a drug has been limited by these same PK issues. Several strategies have been proposed to overcome these limitations, among them glycosylation, which was used in combination with other sequence modifications to produce robust antinociception in mouse models, increased selectivity and potency at the OT receptor, and improved stability in rats.

Postpartum cinsel işlev sorunlarına müdahaleler: Randomize kontrollü çalışmaların sistematik derlemesi

OBJECTIVES: The purpose of this systematic review is to conduct a systematic review of interventions for postpartum sexual function problems. MATERIAL and METHODS: In this systematic review, “PubMed”, “Cochrane”, “Web of Science”, “Science Direct” and “Scopus” databases were searched with the keyword “interventions AND postpartum sexual dysfunction”. The systematic review aimed to include studies published in the last five years, published in English or Turkish, with full text available, and containing interventions for postpartum sexual dysfunction. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was used for study design. The methodological quality of the studies included in the systematic review was evaluated according to the “Joanna Briggs Institute Critical Appraisal Checklist for Randomized Controlled Studies” published by the Joanna Briggs Institute. RESULTS: Eight articles published between 2019–2022 were included in the synthesis phase of the systematic review. It was determined that the “Female Sexual Function Scale” was most commonly used in the studies included in the systematic review. Studies have shown that various interventions such as pelvic floor muscle exercise training, postpartum sexual health programs, and sensory focus technique have been implemented for sexual function problems. It has been determined that pelvic floor muscle exercises, sensory focus technique, pelvic floor muscle trainers, sexual counselling based on PLISSIT and BETTER models, and Postpartum Sexual Health Programs have positive effects on postpartum sexual dysfunctions, while intra-vaginal oxytocin application and far infrared radiation have no effect. CONCLUSION: It has been determined that interventions for postpartum period sexual dysfunctions generally have a positive effect on women’s sexual lives. In order to achieve improvements in postpartum sexual dysfunction, it is recommended to develop various interventions and evaluate them with different measurement tools in larger sample groups. Keywords: postpartum, sexual dysfunction, randomized controlled trial

Comparison of Complication and Post-Operative Infection Rate Between Application of Carbetocin and Oxytocin during Management of Post-Partum Hemorrhage after Caesarean Section

Background: Adverse effects can be produced by carbetocin and oxytocin during management of post-partum hemorrhage after caesarean section. Objective: The purpose of the present study was to compare the adverse effects among women with post-partum hemorrhage after caesarean section. Methodology: This randomized controlled trial was conducted in the Department of Obstetrics and Gynaecology at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from July 2015 to December 2015 for a period of six months. Pregnant women diagnosed on the standard criteria admitted in BSMMU, Dhaka, Bangladesh were selected as study population by consecutive type of sampling. Randomization was performed according to computer generated simple random sampling method. An Uterotonic was an agent used to induce contraction or greater tonicity of the uterus. Then the patients were monitored per operatively and post operatively. All the information was recorded in data collection sheet. Main outcome variables were estimated blood loss. Results: A total number of 96 pregnant women were recruited for this study of which 48 cases were enrolled in group I and the rest of 48 case were enrolled in group II. The mean age with SD of the group I and group II were 24.4±4.7 years and 24.7±3.7 years. In blood transfusion of the study patients, 2(4.2%) patients need blood transfusion in group I and 5(10.4%) in group II (p>0.05). One (2.1%) patients had anaemia in group I and 5(10.4%) in group II. Forty-six (95.8%) patients had average menstrual flow in group I and 40(83.3%) in group II (p>0.05). Considering the side effect, 1(2.1%) patients had nausea in group I and 4(8.3%) in group II. Two (4.2%) patients had vomiting in group I and 5(10.4%) in group II. One (2.1%) patients had headache in group I and 4(8.3%) in group II. Four (8.3%) patients had infection rate in group I and 5(10.4%) in group II (p>0.05). Conclusion: In conclusion blood transfusion, anaemia, vomiting and infection rate are found less in group I than group II. Bangladesh Journal of Infectious Diseases, December 2023;10(2):59-64

A new affine inhibitor of sodium pump thiacalix[4]arene С-1193 increases the intracellular concentration of Ca ions and modifies myometrium contractility

The methods of enzymatic and kinetic analysis were used to demonstrate that thiacalix[4]arene-bis-hydroxymethylphosphonic acid С-1193 had the inhibitory effect (І0.5 = 42.1 ± 0.6 nM) on Na+,K+-ATPase activity in the plasma membrane of myometrium cells with no effect on the relative activity of other ATPases localized in this subcellular structure. The method of confocal microscopy and Са2+-sensitive fluorescent probe fluo-4 were used to demonstrate that thiacalix[4]arene С-1193 increased the intracellular concentration of Ca ions in the immobilized uterine myocytes. The tenzometric studies proved that С-1193 (10 and 100 μМ) increased the isometric phasic contractions, induced via the paths of both electromechanical (depolarization with high-potassium solution) and pharmacomechanical (application of uterotonic hormone oxytocin, neurotransmitter acetylcholine or selective agonist of muscarinic acetylcholine receptors cevimeline) coupling. Application of thiacalix[4]arene С-1193 as a selective and effective inhibitor of Nа+,K+-ATPase may be useful both for studyng the regulation of ion homeostasis in smooth muscle cells and creation of new uterotonics based on the calixarene core. Keywords: contractility mechanokinetics, myometrium, Na+‚K+-АТРase, thiacalix[4]arene

Intranasal oxytocin alleviates comorbid depressive symptoms in neuropathic pain via elevating hippocampal BDNF production in both female and male mice

The comorbidity of pain and depression is frequently observed in patients suffering from chronic pain and depression. However, the comorbid mechanism is not well elucidated and the therapeutic medication is still inadequate. Oxytocin is a neuropeptide synthesized in the hypothalamus. It has been reported to relieve chronic pain and depressive symptoms. However, the analgesic action and mechanisms of oxytocin have mainly been investigated using peripheral or spinal administration. Because of the advantage of intranasal delivery of oxytocin in crossing the blood-brain barrier, we investigated the effect of intranasal application of oxytocin on neuropathic pain and comorbid depressive symptoms in both female and male mice. In female and male mice receiving spared nerve injury (SNI) surgery, intranasal oxytocin (2.4 μg, daily for 28 days) attenuated depression-like behavior, but did not alleviate mechanical hyperalgesia. Intranasal oxytocin not only inhibited the activation of microglia and astrocytes, but also increased the downregulated oxytocin receptor (OTR) expression, reversed the elevated GluN2A, and restored the decreased BDNF expression in the hippocampus. SNI also decreased OTR expression in the spinal cord and increased spinal GluN2A and BDNF. However, intranasal oxytocin treatment did not change the expression levels of OTR, GluN2A, or BDNF in the spinal cord of neuropathic mice. The results suggest that the oxytocin signaling in the hippocampus is involved in the comorbidity of pain and depression, and intranasal oxytocin may have the potential to treat depressive symptoms in neuropathic pain patients.

FRI392 Functional Interrelationship Between Oxytocin And Bone Morphogenetic Proteins In Ovarian Steroidogenesis By Granulosa Cells

Abstract Disclosure: K. Yamamoto: None. Y. Nakano: None. N. Iwata: None. Y. Soejima: None. A. Suyama: None. T. Hasegawa: None. F. Otsuka: None. Oxytocin (OXT) is a neuropeptide that is produced in the hypothalamus and is secreted from the posterior pituitary. OXT has diverse physiological roles mediated by the OXT receptor (OXTR), including not only stimulation of uterine contractions during labor and peripheral functions of milk ejection during lactation but also functions in pair bonding, maternal nurturing, and social behavior related to the action of OXT on the brain. It has been shown that OXT and OXTR are expressed in ovarian granulosa cells (GCs) in several species including humans. Secretion of OXT by bovine GCs is reported to be increased after the preovulatory luteinizing hormone surge, which is coincident with an increase in progesterone secretion and a decrease in secretion of estradiol and androgen, suggesting a functional interrelationship between OXT and ovarian steroidogenesis. It has been demonstrated that application of OXT to cultures of GCs from preovulatory follicles in bovines, marmoset monkeys, and humans led to increases in progesterone production. However, the precise molecular mechanism by which OXT modulates ovarian steroidogenesis in GCs remains unknown. Bone morphogenetic proteins (BMPs), which belong to the transforming growth factor beta (TGF-β) superfamily, play important roles in steroidogenesis and cellular proliferation in ovarian follicles via autocrine/paracrine fashion. BMP ligands and receptors are expressed in a cell-dependent manner in the ovary and have a pivotal role in female fertility. Throughout folliculogenesis, BMPs commonly inhibit follicle-stimulating hormone (FSH)-induced progesterone production, and oocyte-derived factors BMP-6 and BMP-15 are known to act on GCs through BMP receptors and suppress FSH-induced progesterone synthesis. To clarify the reproductive role of OXT in ovarian steroidogenesis and its functional interaction with BMPs, the effects of OXT on ovarian steroidogenesis were investigated by using primary culture of rat GCs and human granulosa KGN cells. Here we found that the OXT receptor was expressed in both rat GCs and human KGN cells and that OXT treatment significantly increased FSH- and forskolin (FSK)-induced progesterone production, but not estradiol production, by rat GCs and KGN cells, respectively. In accordance with the effects of OXT on progesterone production, OXT enhanced mRNA levels of CYP11A1 and HSD3B2 induced by FSK in KGN cells. Of note, OXT enhanced the phosphorylation of SMAD1/5/9 and the mRNA level of ID1 induced by BMP-15, but not those induced by BMP-6, in KGN cells. It was also revealed that OXT application upregulated the expression of BMPR2, a crucial type-II receptor of BMP-15, and enhanced the BMP-15-induced expression of inhibitory SMAD6 by KGN cells. Taken together, it was shown that OXT enhances ovarian progesterone production with upregulation of BMP-15 activity, leading to a fine-tuning of ovarian steroidogenesis. Presentation: Friday, June 16, 2023

Oxytocin alleviates cognitive and memory impairments by decreasing hippocampal microglial activation and synaptic defects via OXTR/ERK/STAT3 pathway in a mouse model of sepsis-associated encephalopathy

BackgroundSepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction, characterized by cognitive and memory impairments closely linked to hippocampal dysfunction. Though it is well-known that SAE is a diffuse brain dysfunction with microglial activation, the pathological mechanisms of SAE are not well established and effective clinical interventions are lacking. Oxytocin (OXT) is reported to have anti-inflammatory and neuroprotective roles. However, the effects of OXT on SAE and the underlying mechanisms are not clear. MethodsSAE was induced in adult C57BL/6J male mice by cecal ligation and perforation (CLP) surgery. Exogenous OXT was intranasally applied after surgery. Clinical score, survivor rate, cognitive and memory behaviors, and hippocampal neuronal and non-neuronal functions were evaluated. Cultured microglia challenged with lipopolysaccharide (LPS) were used to investigate the effects of OXT on microglial functions, including inflammatory cytokines release and phagocytosis. The possible intracellular signal pathways involved in the OXT-induced neuroprotection were explored with RNA sequencing. ResultsHippocampal OXT level decreases, while the expression of OXT receptor (OXTR) increases around 24 h after CLP surgery. Intranasal OXT application at a proper dose increases mouse survival rate, alleviates cognitive and memory dysfunction, and restores hippocampal synaptic function and neuronal activity via OXTR in the SAE model. Intraperitoneal or local administration of the OXTR antagonist L-368,899 in hippocampal CA1 region inhibited the protective effects of OXT. Moreover, during the early stages of sepsis, hippocampal microglia are activated, while OXT application reduces microglial phagocytosis and the release of inflammatory cytokines, thereby exerting a neuroprotective effect. OXT may improve the SAE outcomes via the OXTR-ERK-STAT3 signaling pathway. ConclusionOur study uncovers the dysfunction of the OXT signal in SAE and shows that intranasal OXT application at a proper dose can alleviate SAE outcomes by reducing microglial overactivation, suggests that OXT may be a promising therapeutic approach in managing SAE patients.

Outpatient Cervical Ripening With Misoprostol to Prevent Post-Term Pregnancy: A Double-Blind Randomized Clinical Trial

Outpatient use of misoprostol is assessed in a few studies and usually in low doses and vaginal routes. This study aimed to evaluate cervical ripening by outpatient administration of misoprostol to prevent post-term pregnancy. This randomized clinical trial study was performed on 140 patients that were randomly allocated into two groups: 25 μg sublingual SL (group A) and 50 μg PO misoprostol (group B). The patients were primigravid with a gestational age of 40 weeks, with an amniotic fluid index (AFI) of ≥5 cm, a reactive non-stress test (NST) with no evident uterine contraction, Bishop Score of <8, and no notable past medical history. Patients who had a normal vaginal delivery before 41 weeks were considered successful delivery. Maternal age, the number of misoprostol doses, vaginal examination, type of interventions before delivery, the indication of hospitalization, delivery route, the indication of cesarean section, delivery complications, and neonatal outcomes were compared using SPSS software. P<0.05 was considered statistically significant. group A had mean age of 23.27±4.03 years and Group B had a mean age of 24.61±5.46 years with no significant difference (P=0.223). The number of misoprostol doses (P=0.001), extra misoprostol, and oxytocin application were significantly lower in group B (P=0.003). Maternal and neonatal complications showed no significant difference between the two groups (P>0.05). Outpatient cervical ripening with misoprostol appears to be an optimal method. More prospective studies with higher sample sizes are required to ensure its safety for routine recommendations for cervical ripening to prevent post-term pregnancy.

Application of intranasal oxytocin and affectionate touch reduce subsequent cortisol concentrations in romantic couples: Results from an ecological momentary assessment study

Social interactions and particularly affectionate touch are vital for mental and physical health. Research shows that affectionate touch is associated with release of oxytocin and has calming and stress reducing effects suggesting a regulatory effect of oxytocin on the hypothalamic pituitary adrenal (HPA) axis. Here, we aimed to systematically investigate the effects of repeated intranasal oxytocin administration on salivary cortisol. Furthermore, we focused on the moderating role of couples’ affectionate touch on biopsychological stress outcomes in everyday life. 80 heterosexual romantic couples (N=160 individuals) completed ecologically momentary assessments over five days. Six times per day participants answered smartphone-based questions regarding affectionate touch and momentary stress levels providing concomitant saliva samples for cortisol assessment. Half of the sample was randomly assigned to an instructed positive appraisal task. In a randomized double-blind design, both partners self-administered oxytocin or placebo on five days twice during the early evening. Multilevel analyses showed that oxytocin administration was associated with higher cortisol in the following morning and stronger decreases during the day. Subjectively reported momentary stress was associated with increase of affectionate touch in couples. Moreover, results indicate that participants, who received affectionate touch from their partner showed significantly lower cortisol levels after oxytocin administration. These results suggest that oxytocin administration paired with affectionate touch in romantic couples can influence HPA axis regulation as indicated via diurnal cortisol levels. Thereby, the data shed light on the neuroendocrine underpinnings of the health-promoting effects of intimate social relationships.

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.

Perinatal high-fat diet exposure alters oxytocin and corticotropin releasing factor inputs onto vagal neurocircuits controlling gastric motility.

Perinatal high-fat diet (pHFD) exposure alters the development of vagal neurocircuits that control gastrointestinal (GI) motility and reduce stress resiliency in offspring. Descending oxytocin (OXT; prototypical anti-stress peptide) and corticotropin releasing factor (CRF; prototypical stress peptide) inputs from the paraventricular nucleus (PVN) of the hypothalamus to the dorsal motor nucleus of the vagus (DMV) modulate the GI stress response. How these descending inputs, and their associated changes to GI motility and stress responses, are altered following pHFD exposure are, however, unknown. The present study used retrograde neuronal tracing experiments, cerebrospinal fluid extraction, in vivo recordings of gastric tone, motility and gastric emptying rates, and in vitro electrophysiological recordings from brainstem slice preparations to investigate the hypothesis that pHFD alters descending PVN-DMV inputs and dysregulates vagal brain-gut responses to stress. Compared to controls, rats exposed to pHFD had slower gastric emptying rates and did not respond to acute stress with the expected delay in gastric emptying. Neuronal tracing experiments demonstrated that pHFD reduced the number of PVNOXT neurons that project to the DMV, but increased PVNCRF neurons. Both in vitro electrophysiology recordings of DMV neurons and in vivo recordings of gastric motility and tone demonstrated that, following pHFD, PVNCRF -DMV projections were tonically active, and that pharmacological antagonism of brainstem CRF1 receptors restored the appropriate gastric response to brainstem OXT application. These results suggest that pHFD exposure disrupts descending PVN-DMV inputs, leading to a dysregulated vagal brain-gut response to stress. KEY POINTS: Maternal high-fat diet exposure is associated with gastric dysregulation and stress sensitivity in offspring. The present study demonstrates that perinatal high-fat diet exposure downregulates hypothalamic-vagal oxytocin (OXT) inputs but upregulates hypothalamic-vagal corticotropin releasing factor (CRF) inputs. Both in vitro and in vivo studies demonstrated that, following perinatal high-fat diet, CRF receptors were tonically active at NTS-DMV synapses, and that pharmacological antagonism of these receptors restored the appropriate gastric response to OXT. The current study suggests that perinatal high-fat diet exposure disrupts descending PVN-DMV inputs, leading to a dysregulated vagal brain-gut response to stress.

Retrospective study to assess the effect of epidural analgesia on labor progress and women’s pelvic floor muscle from the perspective of electromyography

Objective Epidural analgesia has been widely used as a form of pain relief during labor and its safety has been gradually recognized. However, few studies of the effect of epidural analgesia on the pelvic floor are known. Thus, we aim to analyze the effect of epidural analgesia on labor progress and women’s pelvic floor muscle from the perspective of electromyography systematically. In addition, obstetric risk factors for dysfunction of pelvic floor muscle after vaginal delivery were also evaluated. Methods Childbirth data of 124 primiparas who gave first birth vaginally in our hospital and their pelvic floor function assessment results at postpartum 7 weeks were retrospectively collected. Pelvic floor muscle electromyogram screenings were performed by a biofeedback electro-stimulant therapy instrument. Results There was no significant difference in the percentage of episiotomy, forceps, artificial rupturing membrane, and the application of oxytocin, except perineal laceration. Woman who implemented epidural analgesia experienced a longer stage of labor. Statistically, there was no significant difference in the total score and pelvic floor muscle strength. The risk factors for the value of the pre-rest phase include the age of pregnant women, the fetal weight, and the length of the second stage while the value of the post-rest phase was only associated with the fetal weight and the length of the second stage. In addition, the value of type I muscles was associated with the gravida and fetal weight while the value of type II muscles was only associated with forceps. The sustained contraction was correlated with the gravida and the total scores had a significant correlation with forceps. Conclusion Epidural analgesia during labor is approved to be a safe and effective procedure to relieve pain with very low side effects on the mode of labor and pelvic floor muscle. The assessment of pelvic floor muscle before pregnancy is beneficial in guiding the better protection of pelvic floor muscle function. According to the evaluation results, the doctors can control the associated risk factors as much as possible to reduce the injury of pregnancy and parturition to the pelvic floor.

Corticotropin-releasing hormone and oxytocin receptors tonically influence nTS activity in rats subjected to chronic intermittent hypoxia

Chronic intermittent hypoxia (CIH) elevates basal sympathetic nervous system activity, blood pressure, respiration and augments their responses to an acute hypoxic challenge. These physiological effects are due, in part, to the integration of several central nuclei. The nucleus tractus solitarii (nTS) is the initial site of peripheral chemoafferent integration and receives input from the paraventricular nucleus of the hypothalamus (PVN) to modulate nTS activity. PVN-to-nTS projections contain oxytocin (OT) and/or corticotropin-releasing hormone (CRH), yet their contribution to nTS activity after CIH is not well understood. We sought to determine the influence of these neuropeptides on nTS synaptic and neuronal activity, hypothesizing they individually increase nTS activity, which is magnified by their co-application, and such responses are enhanced by CIH. Male Sprague-Dawley rats (~3 wks) were exposed to 10d normoxia (21% O2) or CIH (~30s of 6% O2, 10x/hr, 8 h/day). In nTS slices, spontaneous (s) and TS-evoked excitatory postsynaptic currents (EPSCs), membrane potential and action potential discharge (APD) were recorded (n=7,9). Events were examined during OT and CRH or their receptor block (OTR-x, CRHR2-x). Overall, aCSF vehicle did not alter events over the 40-min recording, confirming their stability. Network-driven sEPSCs were enhanced in normoxic slices by only CRH, whereas CRHR2-x did not alter currents. After CIH, the elevation of sEPSCs by CRH was lost and block of OTR and CRHR2-x reduced sEPSC amplitude, indicating a greater tonic activation of these receptors on the nTS neurocircuitry. Afferent (TS)- EPSCs evoked at 0.5 and 20 Hz were not altered by OT or CRH alone nor their receptor block in normoxia. However, CIH elevated TS-EPSCs in response to CRH and CRH+OT, and this effect was greater than normoxia. Block of OTR and CRHR2 after CIH did not alter TS-EPSC amplitude, indicating their minimal tonic influence on sensory integration. Membrane potential was not altered in either group in response to OT and/or CRH application, or their receptor blockade. APD was induced in both groups by current injection. The co-application of OT and CRH increased the APD in normoxic but not CIH neurons. Within the nTS, CIH decreased the expression of OT and CRH (via immunohistochemistry, n = 3-4) and increased OTR and CRHR2 mRNA (via RNA Scope, n=3-4). In agreement with the increased OTR and CRHR2 mRNA expression, calcium imaging in primary dissociated nTS neurons demonstrated enhanced responses to OT+ CRH following CIH vs normoxia (n= 15, 17). Taken together, these data suggest that following CIH, OT and CRH have modality specific effects on nTS activity. NIH R01 HL098602 & R01 HL128454 (DDK). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

May application of oxytocin be relevant in the therapy of perinatal mental disorders?

The perinatal period is a time, when mental diseases occur more frequently, than in other stages of life. Treatment of postpartum depression, psychosis, anxiety is a very hard task. Many psychotropic drugs display a toxic potential during the perinatal period. Hence, it seems that, searching for an alternative pharmacotherapy is relevant. Oxytocin is a substance, that may be successfully used in gynecological treatment. However, its potential is definitely greater. Studies from recent years indicated, that oxytocin is involved in complex pathomechanism of affective disorders. Latest outcomes indicate, that intranasal administration of oxytocin is effective in the treatment of anxiety- and depressive behaviors. The aim of the study is based on the question: Is oxytocin relevant for mental disorders in perinatal period therapy? This question was posed in order to gain psychiatric knowledge about perinatal period’s mental problems and indicates putative novel therapeutic solutions. The research team has performed a review of the studies, searching well-known online scientific databases, including PubMed, ScienceDirect, Scopus and MedLine. Our findings shed light on oxytocin’s significance in a potential new therapy of perinatal mental disorders. Further studies should be focused on intranasal oxytocin administration and its effectivity in the treatment of mentioned diseases, adverse effects, pharmacovigilance, pharmacokinetics and pharmacodynamics. Still, scarce data from clinical studies do not allow the implementation of oxytocin in treatment of perinatal affective disturbances, despite of rationale psychobiological and pharmacological prerequisites. Hence, it is necessary to investigate the relation: oxytocin intervention — perinatal affective disorders.

The Relationship Between Oxytocin and Alcohol Dependence.

The hypothalamic neuropeptide oxytocin (OT) is well known for its prosocial, anxiolytic, and ameliorating effects on various psychiatric conditions, including alcohol use disorder (AUD). In this chapter, we will first introduce the basic neurophysiology of the OT system and its interaction with other neuromodulatory and neurotransmitter systems in the brain. Next, we provide an overview over the current state of research examining the effects of acute and chronic alcohol exposure on the OT system as well as the effects of OT system manipulation on alcohol-related behaviors in rodents and humans. In rodent models of AUD, OT has been repeatedly shown to reduce ethanol consumption, particularly in models of acute alcohol exposure. In humans however, the results of OT administration on alcohol-related behaviors are promising but not yet conclusive. Therefore, we further discuss several physiological and methodological limitations to the effective application of OT in the clinic and how they may be mitigated by the application of synthetic OT receptor (OTR) agonists. Finally, we discuss the potential efficacy of cutting-edge pharmacology and gene therapies designed to specifically enhance endogenous OT release and thereby rescue deficient expression of OT in the brains of patients with severe forms of AUD and other incurable mental disorders.

Activation of oxytocin receptors in mouse GABAergic amacrine cells modulates retinal dopaminergic signaling

BackgroundOxytocin, secreted by oxytocin neurons in the hypothalamus, is an endogenous neuropeptide involved in modulating multiple sensory information processing pathways, and its roles in the brain have been associated with prosocial, maternal, and feeding-related behaviors. Visual information is necessary for initiating these behaviors, with the retina consisting of the first stage in the visual system mediating external stimulus perception. Oxytocin has been detected in the mammalian retina; however, the expression and possible function of oxytocin receptors (OxtR) in the retina remain unknown. Here, we explore the role of oxytocin in regulating visual information processing in the retina.ResultsWe observed that OxtR mRNA and protein are expressed in the mouse retina. With Oxtr-Cre transgenic mice, immunostaining, and fluorescence in situ hybridization, we found that OxtRs are mainly expressed in GABAergic amacrine cells (ACs) in both the inner nuclear layer (INL) and ganglion cell layer (GCL). Further immunoreactivity studies showed that GABAergic OxtR+ neurons are mainly cholinergic and dopaminergic neurons in the INL and are cholinergic and corticotrophin-releasing hormone neurons in the GCL. Surprisingly, a high level of Oxtr mRNAs was detected in retinal dopaminergic neurons, and exogenous oxytocin application activated dopaminergic neurons to elevate the retinal dopamine level. Relying on in vivo electroretinographic recording, we found that activating retinal OxtRs reduced the activity of bipolar cells via OxtRs and dopamine receptors.ConclusionsThese data indicate the functional expression of OxtRs in retinal GABAergic ACs, especially dopaminergic ACs, and expand the interactions between oxytocinergic and dopaminergic systems. This study suggests that visual perception, from the first stage of information processing in the retina, is modulated by hypothalamic oxytocin signaling.

Neuroimaging oxytocin modulation of social reward learning in schizophrenia.

Conventional pharmacological approaches have limited effectiveness for schizophrenia. There is interest in the application of oxytocin, which is involved in social cognition. Clinical trials have yielded mixed results, with a gap in understanding neural mechanisms. To evaluate the behavioural impact of oxytocin administration on a social learning task in individuals with schizophrenia, and elucidate any differential neural activity produced. We recruited 20 clinically stable right-handed men diagnosed with schizophrenia or schizoaffective disorder. In a double-blind cross-over randomised controlled study, 40 IU of oxytocin or placebo were administered before functional magnetic resonance imaging of participants playing a multi-round economic exchange game of trust. Participants had the role of investors (investment trials) receiving repayment on their investments (repayment trials), playing one session against a computer and a second against a player believed to be human. During investment trials, oxytocin increased neural signalling in the right lateral parietal cortex for both human and computer player trials, and attenuated signalling in the right insula for human player trials. For repayment trials, oxytocin elicited signal increases in left insula and left ventral caudate, and a signal decrease in right amygdala during the human player trials; conversely it resulted in right dorsal caudate activation during the computer player trials. We did not find a significant change in behavioural performance associated with oxytocin administration, or any associations with symptoms. During a social learning task oxytocin modulates cortical and limbic substrates of the reward-processing network. These perturbations can be putatively linked to the pathoaetiology of schizophrenia.