A markedly larger number of tyrosine hydroxylase-immunoreactive (TH+: putative dopaminergic) neurons were found in the AVPV of females than in males [65, 72]. This technical report on small and sick newborns, developed by UNICEF and the World Health Organization, outlines what can be done to transform inpatient care for small and sick newborns. Significantly more OXTR-Venus cells were observed in the AVPV of OVX mice that received two weeks of E2 therapy (OVX+E2; 100ng/day; n = 6, 147.6 ± 14.9 cells) compared to OVX mice that received vehicle only (OVX+ Vehicle; n = 6, 5.92 ± 1.24 cells; Fig 6C & 6D; t(10) = 8.25, p<0.0001). While these studies demonstrated the importance of OXTR in the general area of the MPOA for the regulation of maternal behavior, these previous investigations did not provide a detailed neural structure that expresses OXTR. PLoS ONE 14(7): Further studies are necessary to elucidate the role of the OXTR neurons in behavior and physiology. Therefore, the presence of estrogen-dependent and sexually dimorphic distribution of OXTR neurons in the AVPV implies that OXTR-neurons in the AVPV are involved in the induction of maternal behavior; however, behavioral studies using specific knock-out of OXTR in the AVPV is required to confirm such a hypothesis. The concentration of E2 was estimated to release 10 μg of E2 per day at 0.11 μl/hr. No, Is the Subject Area "Heterozygosity" applicable to this article? B. C’è poi il modo di percepire l’amicizia da parte dei bambini. For more information about PLOS Subject Areas, click Moreover, the expression of OXTR in the AVPV is clearly estrogen dependent, because OXTR-Venus was not observed in the AVPV of ovariectomized females, whereas OXTR-Venus expression was restored in OVX that received estrogen therapy. a. Bath applications of oxytocin (100 nM) repeatedly caused membrane depolarization. Differences were considered to be statistically significant at p <0.05. and a CCD camera (ORCA-R2, Hamamatsu Photonics, Hamamatsu). Each osmotic mini-pump contained either 13.9 mM 17β-estradiol (E2, E8875, Sigma-Aldrich, St. Louis, MO) dissolved in a solvent containing dimethyl sulfoxide (DMSO) and 70% Ethanol (1:4, respectively) or vehicle only. Ma l’amicizia, quella duratura, ha i suoi tempi: non è fatta solo di affetto e di condivisione di interessi, ma anche di consapevolezza che quel rapporto è voluto come persistente nel tempo. Chiudendo questo banner, scorrendo questa pagina o cliccando qualunque suo elemento acconsenti all’uso dei cookie. A sparse population of OXTR-Venus cells were also found in the thalamus (PVA). Moreover, TH+ neurons in the AVPV relay a monosynaptic input to oxytocin neurons in the PVN , suggesting that stimulation of oxytocin neurons by TH+ neurons from the AVPV is involved in induction of maternal behavior in females. Questo sito utilizza cookie, anche di terze parti, per migliorare la tua esperienza di navigazione, gestire la pubblicità e compiere analisi statistica del sito. ... icon Double Arrows icon Entrance icon Exclusive icon Exit icon Faq icon Fast Delivery icon … Noi preferiamo il termine amplificati. The application of oxytocin did not cause significant change in membrane potentials of OXTR-Venus (+/+) cells (F(2,4) = 1.33, p = 0.19). Scale bars = 200 μm. Iscriviti alla nostra newsletter. These sampling duration and points were selected because the peak response and plateauing of the membrane potential occurred at these time points in OXTR-Venus cells from heterozygous mice. The present study was conducted to examine whether sex differences exist in the distribution of neurons expressing OXTRs in the POA. Save my name, email, and website in this browser for the next time I comment. b. The brain slices were prepared as described above in Slice preparation / Electrophysiology. After infiltrated with 20% sucrose in 0.1 M PB for cryoprotection for 12 hr., coronal sections were transected at 40 μm by a sliding microtome (Leica SM2010R; Mannheim, Germany). Thus, it is possible that OXTR neurons interact with TH+ neurons within the AVPV to generate a positive feedback loop between TH+ neurons and oxytocin neurons to drive maternal behavior during pregnancy and lactation when the circulating level of estrogen is naturally high . After aspiration, the contents of the micropipette were ejected into an ice-cold 0.5 ml PCR tube and stored at -80°C. © Tutti i diritti riservati - genitoricrescono 2008 - 2018. No detectable OXTR-Venus cells were observed in the anteroventral periventricular nucleus (AVPV) within the MPOA in most of the brain sections from males. These findings suggest that expression of OXTR in the cells of the AVPV is supported by estrogen. B. Click through the PLOS taxonomy to find articles in your field. Differences were considered to be statistically significant at p <0.05. Tissues containing the AVPV were carefully dissected out using a razor blade, were incubated in oxygenated ACSF (35°C) containing Protease Type XIV (1.2 mg/ml: Sigma Chemicals, St Louis, MO, USA) for 20–30 min, and washed in a sodium isethionate solution consisting of (in mM): 140 sodium isethionate, 2 KCl, 4 MgCl2, 23 glucose, 15 HEPES, pH 7.3 (adjusted with 1M NaOH). Autoradiography lacks the ability to identify the precise distribution of OXTRs at the cellular level. A colony was established in a facility at Louisiana State University, and OXTR-Venus mice were backcrossed with C57BL6J mice for at least 10 generations. Funding: The authors received no specific funding for this work. here. At the level of the SON (Fig 2C), intense OXTR-Venus immunoreactivity was found in the amygdala along with areas in the insular and piriform cortex already described above. A study also showed that the treatment with estrogen resulted in significant increase in OXTR binding in the MPOA and lateral septum of virgin female rats . In the thalamus, a group of OXTR-Venus cells was present in the paraventricular thalamic nucleus (PVA). Organizzare gli armadi. Still, diseases like pneumonia, malaria and diarrhoea – along with pregnancy- and birth-related complications – claim the lives of millions of children and mothers every year. Whenever a transgenic approach is used, it is always a concern that the expression of a transgene may interfere with the expression of a native gene or function of the native protein. Ovviamente gli stadi si sovrappongono, proprio perchè ognuno evolve con i suoi tempi da una fase all’altra. The present studies found all OXTR-Venus cells in the AVPV were ERα-immunoreactive. In OXTR-Venus (+/+) cells, the mean membrane potentials before, during, and after the application of oxytocin (100 nM) were -67.57 ± 2.39 mV, -68.73 ± 2.35 mV, and -68.02 ± 2.24 mV, respectively. Plot of the average number of OXTR-Venus neurons in the AVPV/section in the serial sections from the OVLT to SCN in intact, OVX, OVX+E2, and OVX+Vehicle female mice. The mean number of OXTR-Venus cells in the AVPV on the anterior-posterior coordinated sections were plotted to better profile the population of the OXTR-Venus cells in females and males (Fig 3Bi). Brains from young adult (6–8 weeks) virgin heterozygous (+/-) males (n = 6) and females (n = 8) were sectioned coronally from the beginning of the preoptic area to the end of the hypothalamus, and the distribution of OXTR-Venus cells was compared between the sexes. The MPOA neural activity is also necessary for maintenance of maternal behavior . The estrogen dependent expression of OXTR may be mediated by ERα as ERα immunoreactivity was observed in all OXTR-Venus cells in the AVPV; however, this notion must be confirmed by specific manipulation of ERα activity in these OXTR neurons. In coronal sections at the level of the organum vasculosum of the lamina terminalis (OVLT; Fig 2A), OXTR-Venus cells were sparsely distributed in the dorsal-lateral part of the cortex including the cingulate (Cg1 & 2), motor (M1 & M2), and somatosensory (S1 & S2) cortex. https://doi.org/10.1371/journal.pone.0219784.s001, https://doi.org/10.1371/journal.pone.0219784.s002. Yes No, PLOS is a nonprofit 501(c)(3) corporation, #C2354500, based in San Francisco, California, US, https://doi.org/10.1371/journal.pone.0219784. Storia di un gatto e del topo che diventò suo amico, Le relazioni “pericolose” di un amplificato, I migliori regali per bambini di 8 anni - regali-bambini.it, 2020, o l’anno in cui mia figlia ha abbandonato il liceo, L'importanza di un gruppo solidale di genitori. Interestingly, the same treatments, optogenetic stimulation or over expression of tyrosine hydroxylase in TH+ neurons, had no effect on parental care in males . An ANOVA with repeated measures was used to assess the changes in membrane potential in response to oxytocin. The brain sections were subsequently incubated with a secondary antibody (goat anti-rabbit) conjugated with DyLight 594 (Jackson ImmunoResearch, West Grove, PA) for 4 hr at room temperature. The isolated DNA was subsequently genotyped using the following two sets of primers: F (5’-GTTGGGAACAGCGGTGATTA-3’) and R (5'-GGCTCAGGCTTTCTCTACTT-3'). https://doi.org/10.1371/journal.pone.0219784.g003. 55,96. No immunoreactive-cells were observed in the brain section from a wild type mouse. A sexually dimorphic distribution of OXTR-Venus cells occurred in the AVPV where only females had a considerable number of OXTR-Venus cells. Dalle tante classificazioni delle “età dell’amicizia” che si trovano in letteratura, ho ricavato questa schematizzazione, secondo la quale l’amicizia si evolve secondo cinque stadi (ovviamente tutti approssimativi e frutto di generalizzazioni): The neurohypophysial hormone, oxytocin, is synthesized by magnocellular cells located primarily in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. The action of oxytocin on the MPOA is also essential for the onset of maternal behavior at parturition in rats [6, 7]. Writing – original draft, MAGLIA GARA AWAY BAMBINO 2020/21. Ma in fondo questo è un meccanismo che ci portiamo dentro per tutta la vita, solo che poi, “da grandi”, ci facciamo qualche scrupolo in più a gettare le braccia al collo a qualcuno conosciuto da pochi attimi solo perchè abbiamo sentito il feeling giusto e ci facciamo altrattanti scrupoli a dire a qualcuno che conosciamo da tempo “vaiaquelpaese, perchè noi due proprio non ci capiamo più“. The tissue was then triturated in sodium isethionate solution using three successively smaller fire-polished pasteur pipettes to dissociate OXTR-Venus cells. Crescendo, si cerca nell’altro e nella relazione con l’altro qualcosa sempre più complesso ed articolato. A. Fluorescent photomicrographs showing OXTR-Venus immunoreactivity in (a) the preoptic-hypothalamic regions at the level of the AC, (b) 5 sections (200 μm) posterior to the AC, and (c) 15 sections (600 μm) posterior to the AC from a female (top panels) and a male (bottom panels) OXTR-Venus mouse. Writing – review & editing. Estrogen-ERα regulates transcription of the OXTR gene through CG-rich SP1 transcription factor binding sites . The free-floating brain slices were incubated with the primary antibodies against GFP at dilutions of 1:10,000 in PBS containing 0.5% Triton X-100 (PBST) overnight with continuous gentle agitation at 4°C. The oxytocin-mediated depolarization caused repetitive firing. Conceptualization, A sparse population of OXTR-Venus cells was found in the dorsal medial hypothalamic nucleus (DM). Oxytocin triggers social behaviors by binding to oxytocin receptors (OXTRs) in various parts of the brain. These time frames were captured at 30 sec before, 2 min after, and 3 min after the bath application of oxytocin. The amplitudes of depolarization in response to application of oxytocin was significantly greater in heterozygous OXTR-Venus mice than in homozygous OXTR-Venus mice (Fig 4D). Caprio for reading earlier versions of this manuscript, A.C. Rawls and D.N. Cosa si aspettano loro da quello che chiamano “amico” nelle loro diverse età? The groups of mice were euthanized on the same day to avoid age difference becoming a variable. This field guide provides information related to newborn care during the first 28 days of life in humanitarian settings. OXTR-Venus cells were not observed in the SON. In the preoptic areas, magnocellular preoptic nucleus (MCPO) and Septohypothalamic nucleus (Shy) had a cluster of OXTR-Venus cells, whereas not so dense a population of OXTR-Venus cells was observed in the medial preoptic area (MPOA). The sections were mounted in polyvinyl alcohol (PVA) with DABCO. Improving the survival chances of babies, children and their mothers remains an urgent global challenge. In 2019 alone, 6.1 million children under the age of 15 died – including 5.2 million children under the age of 5. The mean number of OXTR-Venus cells/section was significantly higher in females than in males on sections #-3 to #10 (Fig 3ii-a). Yes C. At the level of the supraoptic nucleus (SON), a prominent cluster of OXTR-Venus cells was additionally found in several areas in the amygdala (ACo, CxA, BMA, CeC, CeL, CeM, MeAD) and hypothalamus (AH, SCN, PVN). The brains were then removed and coronal slices (250 μm) containing the hypothalamic periventricular nucleus were collected using a vibrating microtome (Leica VT1200; Leica, Mannheim, Germany). No, Is the Subject Area "Membrane potential" applicable to this article? The present study demonstrated the sexually dimorphic distribution of OXTR neurons in the AVPV in the mouse brain. UNICEF supports countries to provide preventative and curative services for pneumonia, diarrhoea, malaria and other health conditions. Patch electrodes were drawn with a Flaming/Brown micropipette puller (Model P-1000, Sutter Instrument Novato, CA) from borosilicate capillary glass tubing (1.1 mm ID, 1.5 mm OD, Sutter Instruments, Novato, CA) to have resistance of 4-8MΩ when filled with a pipette solution that contained (in mM): 140 K-Gluconate, 1 MgCl2, 10 HEPES, 10 CaCl2, 2 ATP(Mg++), and 0.4 GTP (Na+) and 11 EGTA. In this document, ENAP provides a roadmap to end preventable newborn mortality, reduce disability and end preventable stillbirths by 2030. of Obesity and Internal Inflammation, Fukushima Medical University, Fukushima, Japan, Affiliation Because the expression of OXTR-Venus cells in the AVPV occurred primarily in females, we hypothesized that expression of OXTR in the AVPV is supported by the female gonadal steroid, estrogen. Examples of the effect of oxytocin on membrane potential and the firing pattern of OXTR-Venus (+/-) cells. Kim Hyang Jong, 18 months old, in Jongju City Hospital in the Democratic People’s Republic of Korea, touches her mother's cheek. The number of OXTR-Venus neurons in the AVPV was counted from the level of the OVLT (section -5) to the level of the suprachasmatic nucleus (SCN, section 25) where most of OXTR-Venus neurons were found. AC: anterior commissure; POA: preoptic area. The expression of OXTR in the AVPV is estrogen dependent, as ovariectomy resulted in the absence of OXTR-Venus, whereas estrogen replacement therapy restored the expression of OXTR-Venus. The present study did not quantitatively analyze the density of OXTR-Venus cells in each brain area except the AVPV and MPOA, because such experiments were not within the scope of the study. The presence of the sexually dimorphic expression of OXTR in the AVPV suggests the involvement of OXTR neurons in the AVPV in the regulation of female-specific behavior and/or physiology. Investigation, Affiliation For more information about PLOS Subject Areas, click Interestingly, OXTR expression in numerous other locations were not affected by OVX (data not shown) indicating not all OXTR cells in the brain are estrogen dependent. https://doi.org/10.1371/journal.pone.0219784.g006. No, Is the Subject Area "Ovariectomy" applicable to this article? In the PVN, OXTR-Venus cells were located in the dorsal cap region. Box and whisker plots were used to represent numerical data: mean and median are represented by a filled circle and a line, respectively; the box extends to the quartiles of the data points; the whiskers extend to the furthest data points. Expression of OXTR mRNA was detected in 8 of 10 Venus cells harvested from OXTR-Venus heterozygous (+/-) females, but not detected from any of 4 OXTR-Venus cells obtained from homozygous (+/+) females. In the OXTR-Venus mouse, a part of the OXTR was replaced by Venus. The number of OXTR-Venus cells was not significantly different on any sections between the sexes. Sono un avvocato, ma un giorno ho incontrato Serena e, piano piano, sono diventata tante altre cose. Roles No, Is the Subject Area "Reporter gene assay" applicable to this article? No, Is the Subject Area "Oxytocin" applicable to this article? Sex-differences in the distribution of OXTR cells in the AVPV are unique and strongly indicate the involvement of OXTR cells in the AVPV in the regulation of oxytocin induced sex-specific behaviors and/or physiology. Studi più recenti abbassano l’età in cui si consolida il rapporto d’amicizia, pur ribadendo che la durata nel tempo della relazione ed il suo protrarsi fino all’età adulta, è proprio della pre-adolescenza/adolescenza. A moderate population of OXTR-Venus cells was found in the medial preoptic area (MPOA) surrounding the OVLT. Le relazioni tra coetanei nascono presto, dal primo momento in cui si mettono insieme più bambini, come in un asilo. Moreover, ovariectomy resulted in the absence of OXTR-Venus expression in the AVPV, whereas estrogen replacement therapy restored OXTR-Venus expression. However, in stark contrast to all other brain areas where OXTR-Venus cells were found in both sexes, the presence of OXTR-Venus cells in the AVPV occurs nearly exclusively in females. In contrast to transgenic reporter models, which use random integration of a reporter gene that could end up anywhere in the host genome, this OXTR-Venus mouse line is an OXTR knock-in model in which Venus is inserted into the locus exactly where OXTR is normally located . Copyright: © 2019 Sharma et al. Supervision, 55,96. Digital images were minimally altered in ImageJ software (Bethesda, NIH) with changes in dynamic range. These findings imply that DNA methylation affects the interaction between SP1, ERα and their binding sites in the OXTR promoter . In contrast to the dorsal-lateral regions of the cortex, clusters of OXTR-Venus cells were found in several areas in the piriform (Pir) and insular cortex, namely the dorsal endopiriform claustrum (DEn), the intermediate endopiriform claustrum (IEn), the dorsal and ventral parts of the agranular insular cortex (AID & AIV).
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