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Frontiers in Neural Circuits 2023Parental care plays a crucial role in the physical and mental well-being of mammalian offspring. Although sexually naïve male mice, as well as certain strains of female... (Review)
Review
Parental care plays a crucial role in the physical and mental well-being of mammalian offspring. Although sexually naïve male mice, as well as certain strains of female mice, display aggression toward pups, they exhibit heightened parental caregiving behaviors as they approach the time of anticipating their offspring. In this Mini Review, I provide a concise overview of the current understanding of distinct limbic neural types and their circuits governing both aggressive and caregiving behaviors toward infant mice. Subsequently, I delve into recent advancements in the understanding of the molecular, cellular, and neural circuit mechanisms that regulate behavioral plasticity during the transition to parenthood, with a specific focus on the sex steroid hormone estrogen and neural hormone oxytocin. Additionally, I explore potential sex-related differences and highlight some critical unanswered questions that warrant further investigation.
Topics: Humans; Mice; Male; Animals; Female; Paternal Behavior; Aggression; Oxytocin; Mammals
PubMed: 38298741
DOI: 10.3389/fncir.2023.1340497 -
Archives of Dermatological Research Nov 2023In the recent decades, prostaglandins were recommended as a new therapeutic modality of stable vitiligo with promising efficacy. Therefore, we designed the current work...
In the recent decades, prostaglandins were recommended as a new therapeutic modality of stable vitiligo with promising efficacy. Therefore, we designed the current work to compare the significance of two different subtypes of prostaglandins [prostaglandin E2 (PGE2) versus prostaglandin F2 alpha (PGF2α)], assisted with NB-UVB phototherapy, in treatment of stable vitiligo. This study was conducted on 30 patients with stable non-segmental vitiligo. Three approximately similar vitiliginous areas were chosen in each patient and assigned into 3 groups. Each group treated with intradermal injection of either PGE2 (group I), PGF2α (group II), or saline as placebo (group III) at frequency once/week for 12 weeks. Concomitantly, all groups received NB-UVB phototherapy twice weekly for 3 months. The outcomes of this study discovered that the therapeutic efficacy of intradermal injection of either PGE2 or PGF2α assisted with NB-UVB phototherapy was comparable with non-significant difference between them in spite of being significantly higher than NB-UVB alone. However, there were a significantly earlier onset of repigmentation and higher degree of satisfaction regarding areas treated with PGE2 than those treated with PGF2α. In conclusion, both PGF2α and PGE2 intradermal injection could be considered as quite simple and affordable techniques in the treatment of stable vitiligo with no reported side effects and good patient satisfaction.
Topics: Humans; Dinoprostone; Dinoprost; Vitiligo; Hypopigmentation; Prostaglandins; Ultraviolet Therapy
PubMed: 37594537
DOI: 10.1007/s00403-023-02700-8 -
Frontiers in Endocrinology 2024During parturition and the immediate post-partum period there are two opposite, yet interdependent and intertwined systems that are highly active and play a role in...
During parturition and the immediate post-partum period there are two opposite, yet interdependent and intertwined systems that are highly active and play a role in determining lifelong health and behaviour in both the mother and her infant: the stress and the anti-stress (oxytocin) system. Before attempting to understand how the environment around birth determines long-term health trajectories, it is essential to understand how these two systems operate and how they interact. Here, we discuss together the hormonal and neuronal arms of both the hypothalamic-pituitary-adrenal (HPA) axis and the oxytocinergic systems and how they interact. Although the HPA axis and glucocorticoid stress axis are well studied, the role of oxytocin as an extremely powerful anti-stress hormone deserves more attention. It is clear that these anti-stress effects depend on oxytocinergic nerves emanating from the supraoptic nucleus (SON) and paraventricular nucleus (PVN), and project to multiple sites at which the stress system is regulated. These, include projections to corticotropin releasing hormone (CRH) neurons within the PVN, to the anterior pituitary, to areas involved in sympathetic and parasympathetic nervous control, to NA neurons in the locus coeruleus (LC), and to CRH neurons in the amygdala. In the context of the interaction between the HPA axis and the oxytocin system birth is a particularly interesting period as, for both the mother and the infant, both systems are very strongly activated within the same narrow time window. Data suggest that the HPA axis and the oxytocin system appear to interact in this early-life period, with effects lasting many years. If mother-child skin-to-skin contact occurs almost immediately postpartum, the effects of the anti-stress (oxytocin) system become more prominent, moderating lifelong health trajectories. There is clear evidence that HPA axis activity during this time is dependent on the balance between the HPA axis and the oxytocin system, the latter being reinforced by specific somatosensory inputs, and this has long-term consequences for stress reactivity.
Topics: Animals; Female; Humans; Pregnancy; Hypothalamo-Hypophyseal System; Oxytocin; Pituitary-Adrenal System; Stress, Physiological; Stress, Psychological; Yin-Yang
PubMed: 38689729
DOI: 10.3389/fendo.2024.1272270 -
BMC Women's Health Jul 2023Myomectomy is the preferred surgical approach to manage uterine fibroids. However, uterine fibroids are highly vascular tumors and, consequently, extremely susceptible... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Myomectomy is the preferred surgical approach to manage uterine fibroids. However, uterine fibroids are highly vascular tumors and, consequently, extremely susceptible to problems from myomectomy-related hemorrhage. Hence, we aim to compare oxytocin efficacy and safety profile versus tranexamic acid (TA) with ethamsylate for reducing bleeding during myomectomy.
METHODS
This randomized, double-blinded multicenter study was performed between 20 August 2020 and 20 October 2020 at El-Galaa Teaching Hospital, El Hussein University Hospital, Al-Azhar University Hospitals of Assiut, and Al-Azhar University Hospitals of Damietta. One hundred and eighty patients were enrolled and divided into three groups: group (1) received an injection of 30 IU of oxytocin in 500 ml of normal saline; group (2) received injections of 1 g of TA, 250 mg of Ethamsylate, and 110 ml of normal saline IV; and group (3) received an injection of 110 ml of normal saline IV just before surgical incision.
RESULTS
In 180 premenopausal women, oxytocin and TA with ethamsylate had no significant value in lowering intraoperative blood loss compared with the placebo for abdominal myomectomy (666.25 ± 183.03, 630.72 ± 145.83, and 646.67 ± 168.92, respectively (P = 0.506)). Non-significant trends were observed for a reduction in operation time (P = 0.760), intra/postoperative blood transfusion (P = 0.624), hospital stay (P = 0.986), postoperative fever (P = 0.659), and wound infection (P = 1).
CONCLUSION
Oxytocin and TA with ethamsylate had no significant value in lowering intraoperative blood loss compared with the placebo for abdominal myomectomy which opens a new question about the role of the use of the hemostatic drug during myomectomy especially in centers with limited resources and had higher rates.
TRIAL REGISTRATION
The study was registered on Pan African Clinical Trials Registry with the following number: PACTR202008739887429 and was approved on 24/08/2020.
Topics: Humans; Female; Ethamsylate; Tranexamic Acid; Uterine Myomectomy; Oxytocin; Blood Loss, Surgical; Saline Solution; Leiomyoma
PubMed: 37516864
DOI: 10.1186/s12905-023-02549-z -
The Journal of Neuroscience : the... Jan 2024Peripheral sensitization is one of the primary mechanisms underlying the pathogenesis of chronic pain. However, candidate molecules involved in peripheral sensitization...
Peripheral sensitization is one of the primary mechanisms underlying the pathogenesis of chronic pain. However, candidate molecules involved in peripheral sensitization remain incompletely understood. We have shown that store-operated calcium channels (SOCs) are expressed in the dorsal root ganglion (DRG) neurons. Whether SOCs contribute to peripheral sensitization associated with chronic inflammatory pain is elusive. Here we report that global or conditional deletion of Orai1 attenuates Complete Freund's adjuvant (CFA)-induced pain hypersensitivity in both male and female mice. To further establish the role of Orai1 in inflammatory pain, we performed calcium imaging and patch-clamp recordings in wild-type (WT) and Orai1 knockout (KO) DRG neurons. We found that SOC function was significantly enhanced in WT but not in Orai1 KO DRG neurons from CFA- and carrageenan-injected mice. Interestingly, the Orai1 protein level in L3/4 DRGs was not altered under inflammatory conditions. To understand how Orai1 is modulated under inflammatory pain conditions, prostaglandin E2 (PGE2) was used to sensitize DRG neurons. PGE2-induced increase in neuronal excitability and pain hypersensitivity was significantly reduced in Orai1 KO mice. PGE2-induced potentiation of SOC entry (SOCE) was observed in WT, but not in Orai1 KO DRG neurons. This effect was attenuated by a PGE2 receptor 1 (EP1) antagonist and mimicked by an EP1 agonist. Inhibition of Gq/11, PKC, or ERK abolished PGE2-induced SOCE increase, indicating PGE2-induced SOCE enhancement is mediated by EP1-mediated downstream cascade. These findings demonstrate that Orai1 plays an important role in peripheral sensitization. Our study also provides new insight into molecular mechanisms underlying PGE2-induced modulation of inflammatory pain. Store-operated calcium channel (SOC) Orai1 is expressed and functional in dorsal root ganglion (DRG) neurons. Whether Orai1 contributes to peripheral sensitization is unclear. The present study demonstrates that Orai1-mediated SOC function is enhanced in DRG neurons under inflammatory conditions. Global and conditional deletion of Orai1 attenuates complete Freund's adjuvant (CFA)-induced pain hypersensitivity. We also demonstrate that prostaglandin E2 (PGE2) potentiates SOC function in DRG neurons through EP1-mediated signaling pathway. Importantly, we have found that Orai1 deficiency diminishes PGE2-induced SOC function increase and reduces PGE2-induced increase in neuronal excitability and pain hypersensitivity. These findings suggest that Orai1 plays an important role in peripheral sensitization associated with inflammatory pain. Our study reveals a novel mechanism underlying PGE2/EP1-induced peripheral sensitization. Orai1 may serve as a potential target for pathological pain.
Topics: Animals; Female; Male; Mice; Calcium; Calcium Channels; Dinoprostone; Freund's Adjuvant; Ganglia, Spinal; ORAI1 Protein; Pain
PubMed: 37952941
DOI: 10.1523/JNEUROSCI.0329-23.2023 -
Bone Research Mar 2024Bone is a mechanosensitive tissue and undergoes constant remodeling to adapt to the mechanical loading environment. However, it is unclear whether the signals of bone...
Bone is a mechanosensitive tissue and undergoes constant remodeling to adapt to the mechanical loading environment. However, it is unclear whether the signals of bone cells in response to mechanical stress are processed and interpreted in the brain. In this study, we found that the hypothalamus of the brain regulates bone remodeling and structure by perceiving bone prostaglandin E2 (PGE2) concentration in response to mechanical loading. Bone PGE2 levels are in proportion to their weight bearing. When weight bearing changes in the tail-suspension mice, the PGE2 concentrations in bones change in line with their weight bearing changes. Deletion of cyclooxygenase-2 (COX2) in the osteoblast lineage cells or knockout of receptor 4 (EP4) in sensory nerve blunts bone formation in response to mechanical loading. Moreover, knockout of TrkA in sensory nerve also significantly reduces mechanical load-induced bone formation. Moreover, mechanical loading induces cAMP-response element binding protein (CREB) phosphorylation in the hypothalamic arcuate nucleus (ARC) to inhibit sympathetic tyrosine hydroxylase (TH) expression in the paraventricular nucleus (PVN) for osteogenesis. Finally, we show that elevated PGE2 is associated with ankle osteoarthritis (AOA) and pain. Together, our data demonstrate that in response to mechanical loading, skeletal interoception occurs in the form of hypothalamic processing of PGE2-driven peripheral signaling to maintain physiologic bone homeostasis, while chronically elevated PGE2 can be sensed as pain during AOA and implication of potential treatment.
Topics: Animals; Mice; Dinoprostone; Ankle; Interoception; Brain; Pain; Osteoarthritis
PubMed: 38443372
DOI: 10.1038/s41413-024-00316-w -
The Journal of Biological Chemistry Apr 2024Regulators of G protein signaling (RGS) proteins constrain G protein-coupled receptor (GPCR)-mediated and other responses throughout the body primarily, but not...
Regulators of G protein signaling (RGS) proteins constrain G protein-coupled receptor (GPCR)-mediated and other responses throughout the body primarily, but not exclusively, through their GTPase-activating protein activity. Asthma is a highly prevalent condition characterized by airway hyper-responsiveness (AHR) to environmental stimuli resulting in part from amplified GPCR-mediated airway smooth muscle contraction. Rgs2 or Rgs5 gene deletion in mice enhances AHR and airway smooth muscle contraction, whereas RGS4 KO mice unexpectedly have decreased AHR because of increased production of the bronchodilator prostaglandin E2 (PGE2) by lung epithelial cells. Here, we found that knockin mice harboring Rgs4 alleles encoding a point mutation (N128A) that sharply curtails RGS4 GTPase-activating protein activity had increased AHR, reduced airway PGE2 levels, and augmented GPCR-induced bronchoconstriction compared with either RGS4 KO mice or WT controls. RGS4 interacted with the p85α subunit of PI3K and inhibited PI3K-dependent PGE2 secretion elicited by transforming growth factor beta in airway epithelial cells. Together, these findings suggest that RGS4 affects asthma severity in part by regulating the airway inflammatory milieu in a G protein-independent manner.
Topics: Animals; Humans; Mice; Asthma; Bronchoconstriction; Dinoprostone; Epithelial Cells; GTPase-Activating Proteins; Mice, Knockout; Phosphatidylinositol 3-Kinases; Respiratory Hypersensitivity; RGS Proteins; Cell Line
PubMed: 38432633
DOI: 10.1016/j.jbc.2024.107127 -
European Journal of Pharmacology Sep 2023Interstitial cells of Cajal generate slow wave gastric electrical activity, initiating spontaneous muscle contractions. This becomes dysrhythmic during nausea when...
BACKGROUND
Interstitial cells of Cajal generate slow wave gastric electrical activity, initiating spontaneous muscle contractions. This becomes dysrhythmic during nausea when [Arg]-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 APPROACH
Spontaneous and electrically-evoked (EFS) contractions were measured in rat forestomach and antrum circular muscle. Custom software defined spontaneous contractions by analysing eight motility parameters.
RESULTS
The 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 M), atropine (10 M) and L-NAME (3 × 10 M). In both regions, AVP (pEC∼9.0) and OT (∼0.5 log-unit less potent) caused contraction (greater in antrum), competitively antagonized by, respectively, SR49059 (pK∼9.5) and L371257 (pK∼9.0), reduced by tetrodotoxin but unaffected by atropine. In the antrum, AVP and OT (∼2 log-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.
CONCLUSION
Irregular spontaneous contractions of gastric antrum suggest variable ICC-muscle coupling. AVP and less potently, OT, enhanced frequency and force of contractions via V 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.
Topics: Animals; Rats; Arginine; Arginine Vasopressin; Atropine; Oxytocin; Receptors, Oxytocin; Receptors, Vasopressin; Stomach; Tetrodotoxin; Vasopressins
PubMed: 37429518
DOI: 10.1016/j.ejphar.2023.175906 -
What do healthcare providers think of the quality of uterotonics? A mixed-methods systematic review.BMJ Open Oct 2023To synthesise evidence on the perceptions of healthcare providers (HCPs) about the quality of oxytocin and misoprostol available in their settings, and their actions as...
OBJECTIVES
To synthesise evidence on the perceptions of healthcare providers (HCPs) about the quality of oxytocin and misoprostol available in their settings, and their actions as a result of these perceptions.
DESIGN
Mixed-methods systematic review.
ELIGIBILITY CRITERIA
We included quantitative and qualitative studies reporting HCPs' perceptions about oxytocin or misoprostol quality.
DATA SOURCES
We searched CINAHL, Cochrane Library, Ebscohost, Embase, PubMed, Global Index Medicus, Portal regional BVS, PsycNET, Scopus and Web of Science from inception to 31 March 2022 and grey literature.
RISK OF BIAS
We used the Center for Evidence-Based Management critical appraisal tool for surveys. For qualitative studies, we used the Critical Appraisal Skills Programme tool.
DATA EXTRACTION AND SYNTHESIS
Two independent reviewers performed study selection, data extraction and quality assessment. We conducted separate quantitative and qualitative syntheses and integrated the evidence into a narrative synthesis (convergent segregated review design).
RESULTS
We included five (three quantitative and two qualitative) studies, of moderate or high quality, conducted in low-income and middle-income countries (LMICs). In the three quantitative studies (N=7065 participants), 8.2-21.3% of HCPs had experienced problems due to known/suspected low-quality oxytocin and 3.3% due to low-quality misoprostol. In the two qualitative studies, perception of oxytocin quality varied. In quantitative studies, when confronted with suspected/known low-quality oxytocin, 29-78% of HCPs would inform a supervisor, 62% would document this in writing, 45-54% would change to another drug and 5-37% would double the dose of oxytocin. Qualitative evidence suggests that many HCPs do not formally report suspected low-quality oxytocin or misoprostol, and use higher doses or additional uterotonics.
CONCLUSIONS
A proportion of HCPs from LMICs perceive oxytocin to be of low quality. There is very limited evidence on their perceptions about misoprostol. Many HCPs do not report suspected low-quality uterotonics but change to another medicine or double the dose of oxytocin.
PROSPERO REGISTRATION NUMBER
CRD42022323812.
Topics: Female; Humans; Oxytocin; Misoprostol; Postpartum Hemorrhage; Health Personnel
PubMed: 37899165
DOI: 10.1136/bmjopen-2022-068442 -
Biology of Sex Differences Oct 2023The supraoptic nucleus (SON) of the hypothalamus contains magnocellular neurosecretory cells that secrete the hormones vasopressin and oxytocin. Sex differences in SON...
BACKGROUND
The supraoptic nucleus (SON) of the hypothalamus contains magnocellular neurosecretory cells that secrete the hormones vasopressin and oxytocin. Sex differences in SON gene expression have been relatively unexplored. Our study used spatially resolved transcriptomics to visualize gene expression profiles in the SON of adult male (n = 4) and female (n = 4) Sprague-Dawley rats using Visium Spatial Gene Expression (10x Genomics).
METHODS
Briefly, 10-μm coronal sections (~ 4 × 4 mm) containing the SON were collected from each rat and processed using Visium slides and recommended protocols. Data were analyzed using 10x Genomics' Space Ranger and Loupe Browser applications and other bioinformatic tools. Two unique differential expression (DE) analysis methods, Loupe Browser and DESeq2, were used.
RESULTS
Loupe Browser DE analysis of the SON identified 116 significant differentially expressed genes (DEGs) common to both sexes (e.g., Avp and Oxt), 31 significant DEGs unique to the males, and 73 significant DEGs unique to the females. DESeq2 analysis revealed 183 significant DEGs between the two groups. Gene Ontology (GO) enrichment and pathway analyses using significant genes identified via Loupe Browser revealed GO terms and pathways related to (1) neurohypophyseal hormone activity, regulation of peptide hormone secretion, and regulation of ion transport for the significant genes common to both males and females, (2) G signaling/G-protein mediated events for the significant genes unique to males, and (3) potassium ion transport/voltage-gated potassium channels for the significant genes unique to females, as some examples. GO/pathway analyses using significant genes identified via DESeq2 comparing female vs. male groups revealed GO terms/pathways related to ribosomal structure/function. Ingenuity Pathway Analysis (IPA) identified additional sex differences in canonical pathways (e.g., 'Mitochondrial Dysfunction', 'Oxidative Phosphorylation') and upstream regulators (e.g., CSF3, NFKB complex, TNF, GRIN3A).
CONCLUSION
There was little overlap in the IPA results for the two different DE methods. These results suggest sex differences in SON gene expression that are associated with cell signaling and ribosomal pathways.
Topics: Rats; Female; Male; Animals; Supraoptic Nucleus; Rats, Sprague-Dawley; Sex Characteristics; Transcriptome; Oxytocin; Signal Transduction
PubMed: 37858270
DOI: 10.1186/s13293-023-00554-3