scholarly journals Dynamic Changes in Oxytocin Receptor Expression and Activation at Parturition in the Rat Brain

Endocrinology ◽  
2007 ◽  
Vol 148 (10) ◽  
pp. 5095-5104 ◽  
Author(s):  
Simone L. Meddle ◽  
Valerie R. Bishop ◽  
Effimia Gkoumassi ◽  
Fred W. van Leeuwen ◽  
Alison J. Douglas
Keyword(s):  
Mrna Expression ◽  
Paraventricular Nucleus ◽  
Maternal Behavior ◽  
Brain Regions ◽  
Oxytocin Receptor ◽  
Lateral Septum ◽  
Receptor Expression ◽  
Olfactory Bulbs ◽  
Bed Nucleus ◽  
The Brain

Oxytocin plays a pivotal role in rat parturition, acting within the brain to facilitate its own release in the supraoptic nucleus (SON) and paraventricular nucleus, and to stimulate maternal behavior. We investigated oxytocin receptor (OTR) expression and activation perinatally. Using a 35S-labeled riboprobe complementary to OTR mRNA, OTR expression was quantified in proestrus virgin, 21- and 22-day pregnant, parturient (90 min. from pup 1 birth), and postpartum (4–12 h from parturition) rats. Peak OTR mRNA expression was observed at parturition in the SON, brainstem regions, medial preoptic area (mPOA), bed nucleus of the stria terminalis (BnST), and olfactory bulbs, but there was no change in the paraventricular nucleus and lateral septum. OTR mRNA expression was increased on the day of expected parturition in the SON and brainstem, suggesting that oxytocin controls the pathway mediating input from uterine signals. Likewise, OTR mRNA expression was increased in the mPOA and BnST during labor/birth. In the olfactory bulbs and medial amygdala, parturition induced increased OTR mRNA expression compared with pre-parturition, reflecting their immediate response to new stimuli at birth. Postpartum OTR expression in all brain regions returned to levels observed in virgin rats. Parturition significantly increased the number of double-immunolabeled cells for Fos and OTR within the SON, brainstem, BnST, and mPOA regions compared with virgin rats. Thus, there are dynamic region-dependent changes in OTR-expressing cells at parturition. This altered OTR distribution pattern in the brain perinatally reflects the crucial role oxytocin plays in orchestrating both birth and maternal behavior.

scholarly journals Heterotrimeric G Proteins of the Gq/11 Family Are Crucial for the Induction of Maternal Behavior in Mice

2004 ◽  
Vol 24 (18) ◽  
pp. 8048-8054 ◽  
Author(s):  
Nina Wettschureck ◽  
Alexandra Moers ◽  
Tuula Hamalainen ◽  
Thomas Lemberger ◽  
Günther Schütz ◽  
...  
Keyword(s):  
G Proteins ◽  
Maternal Behavior ◽  
Motor Behavior ◽  
Oxytocin Receptor ◽  
Lateral Septum ◽  
Heterotrimeric G Proteins ◽  
Bed Nucleus ◽  
The Central Nervous System ◽  
Gland Function

ABSTRACT Heterotrimeric G proteins of the Gq/11 family transduce signals from a variety of neurotransmitter receptors and have therefore been implicated in several functions of the central nervous system. To investigate the potential role of Gq/11 signaling in behavior, we generated mice which lack the α-subunits of the two main members of the Gq/11 family, Gαq and Gα11, selectively in the forebrain. We show here that forebrain Gαq/11-deficient females do not display any maternal behavior such as nest building, pup retrieving, crouching, or nursing. However, olfaction, motor behavior and mammary gland function are normal in forebrain Gαq/11-deficient females. We used c-fos immunohistochemistry to investigate pup-induced neuronal activation in different forebrain regions and found a significant reduction in the medial preoptic area, the bed nucleus of stria terminalis, and the lateral septum both in postpartum females and in virgin females after foster pup exposure. Pituitary function, especially prolactin release, was normal in forebrain Gαq/11-deficient females, and activation of oxytocin receptor-positive neurons in the hypothalamus did not differ between genotypes. Our findings show that Gq/11 signaling is indispensable to the neuronal circuit that connects the perception of pup-related stimuli to the initiation of maternal behavior and that this defect cannot be attributed to either reduced systemic prolactin levels or impaired activation of oxytocin receptor-positive neurons of the hypothalamus.

Androgen manipulation and vasopressin binding in the rat brain and peripheral organs

1994 ◽  
Vol 130 (3) ◽  
pp. 291-296 ◽  
Author(s):  
Xin Gao ◽  
Paddy Phillips ◽  
Brian Oldfield ◽  
Deborah Trinder ◽  
John Risvanis ◽  
...  
Keyword(s):  
Rat Brain ◽  
Receptor Binding ◽  
Brain Regions ◽  
Lateral Septum ◽  
Plasma Testosterone ◽  
Bed Nucleus ◽  
Peripheral Organs ◽  
Oxytocin Receptors ◽  
The University ◽  
The Brain

Gao X, Phillips P, Oldfield B, Trinder D, Risvanis J, Stephenson J, Johnston C. Androgen manipulation and vasopressin binding in the rat brain and peripheral organs. Eur J Endocrinol 1994;130:291–6. ISSN 0804–4643 It is now widely recognized that there is a sexual dimorphism in the development of arginine vasopressin (AVP) immunoreactivity in certain parts of the brain, and that changes in brain AVP immunoreactivity change with manipulation of androgen status. The aim of this experiment was to determine specifically any AVP receptor changes in response to manipulation of androgen levels using a selective V1 antagonist radioligand. Following castration, plasma testosterone levels fell and AVP immunoreactivity was reduced in the lateral septum and bed nucleus of the stria terminalis. With testosterone supplementation in castrated animals, the immunoreactivity in these regions was restored to a higher degree than in sham-operated animals. Central and peripheral V1 AVP receptor binding (as determined using the selective AVP V1 antagonist radioligand [125I](d(CH2)5,sarcosine7)AVP was not changed in any of the brain regions studied or in liver or kidney membranes from the three groups. This study demonstrates that there is no change in brain AVP receptor binding despite changes in regional AVP immunoreactivity in the brain, and excludes any confounding interaction with changes in oxytocin receptors. P A Phillips, Department of Medicine, The University of Melbourne, Austin Hospital, Heidelberg, Victoria 3084, Australia

scholarly journals The Alterations of Endometrial and Myometrial Receptivity in Early Pregnant Gilts in Response to Estrus Induction With PMSG/hCG

2021 ◽  
Author(s):  
Magdalena Szymanska ◽  
Agnieszka Blitek
Keyword(s):  
Mrna Expression ◽  
Standard Procedure ◽  
Oxytocin Receptor ◽  
Hormonal Control ◽  
Receptor Expression ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Uterine Receptivity ◽  
Swine Industry ◽  
Junction Protein

Abstract Background: The hormonal control of ovulation has become a standard procedure in the swine industry. However, exogenous gonadotropins can be detrimental to reproductive function, affecting follicle development, corpus luteum formation, and embryo development and survival. Much less is known about uterine receptivity in gilts with induced estrus. Therefore, our objective was to determine the effect of estrus induction with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) on the expression of steroid, prostaglandin, cytokine, and oxytocin receptors, as well as nuclear factor kappa B subunit 1 (NFKB1), peroxisome proliferator activated receptor gamma (PPARG), and gap junction protein alpha 1 (GJA1), in the endometrium and myometrium of early pregnant gilts. Twenty prepubertal gilts received 750 IU PMSG and 500 IU hCG 72 h later, while eighteen prepubertal gilts in the control group were observed daily for estrus behavior. All gilts were inseminated in their first estrus and slaughtered on days 10, 12, and 15 of pregnancy to collect uterine tissues for mRNA expression analyses using real-time PCR.Results: Estrus induction did not affect progesterone receptor expression in either uterine tissue. In the endometrium, greater mRNA expression of estrogen receptors (ESR1 and ESR2), androgen receptor (AR), prostaglandin (PG) E2 receptors (PTGER2 and PTGER4), PGF2α receptor (PTGFR), interleukin 6 receptor (IL6R), tumor necrosis factor α receptors (TNFRSF1A and TNFRSF1B), and oxytocin receptor (OXTR) was detected in the control than in the PMSG/hCG-treated gilts (P < 0.05). In the myometrium, concentrations of AR, PTGER2, PTGFR, and NFKB1 transcripts were lower, while PGI2 receptor and PPARG transcripts were elevated in gilts with gonadotropin-induced estrus as compared with naturally ovulated gilts (P < 0.05). Furthermore, the administration of PMSG/hCG resulted in the greater expression of GJA1 mRNA in both the endometrium and myometrium of day 15 pregnant gilts (P < 0.05). Conclusions: Estrus induction with PMSG/hCG in prepubertal gilts may affect steroid, prostaglandin, cytokine, and oxytocin receptor expression in the endometrium and myometrium, thereby altering uterine receptivity to local or systemic factors. This may, in turn, contribute to disorders in embryo-maternal interactions and the process of implantation.

scholarly journals The effects of lipopolysaccharide and interleukins-1alpha, -2 and -6 on oxytocin receptor expression and prostaglandin production in bovine endometrium

2001 ◽  
Vol 168 (3) ◽  
pp. 497-508 ◽  
Author(s):  
ST Leung ◽  
Z Cheng ◽  
EL Sheldrick ◽  
K Derecka ◽  
K Derecka ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Luteal Phase ◽  
Acute Phase Proteins ◽  
Chinese Hamster Ovary Cells ◽  
In Situ Hybridisation ◽  
Chinese Hamster ◽  
Oxytocin Receptor ◽  
Receptor Expression ◽  
Prostaglandin Production ◽  
Late Luteal Phase

Up-regulation of endometrial oxytocin receptor (OTR) expression followed by an increase in pulsatile endometrial prostaglandin (PG) F(2alpha) secretion causes luteolysis in cattle. Inhibition of luteolysis is essential for the maternal recognition of pregnancy but also occurs in association with endometritis. The factors regulating OTR expression at this time are unclear. The OTR gene promoter region contains binding elements for acute phase proteins but their function has not been established. This study investigated the effects of various cytokines on OTR expression and on PGF(2alpha) and PGE(2) production in explant cultures of bovine endometrium. Endometrium was collected in the late luteal phase (mean day of cycle 15.4+/-0.50) or early luteolysis (mean day of cycle 16.4+/-0.24) as determined by the initial concentration of endometrial OTR. Explants were treated for 48 h with: (i) lipopolysaccharide (LPS) and/or dexamethasone (DEX), (ii) ovine interferon-tau (oIFN-tau), or (iii) human recombinant interleukin (IL)-1alpha, -2 or -6. OTR mRNA was then measured in the explants by in situ hybridisation and the medium was collected for measurement of PGF(2alpha) and PGE(2) by RIA. LPS treatment stimulated production of PGF(2alpha), whereas DEX either alone or in combination with LPS was inhibitory to both PGF(2alpha) and PGE(2). Neither of these treatments altered OTR mRNA expression. oIFN-tau reduced OTR mRNA expression but stimulated production of both PGF(2alpha) and PGE(2). In endometrial samples collected in the late luteal phase, IL-1alpha, -2 and -6 all inhibited OTR mRNA expression, but IL-1alpha and -2 both stimulated PGF(2alpha) production. In contrast, when endometrium was collected in early luteolysis, none of the interleukins altered OTR expression or caused a significant stimulation of PGF(2alpha) production but IL-2 increased PGE(2). Neither IL-1alpha nor -2 altered OTR promoter activity in Chinese hamster ovary cells transfected with a bovine OTR promoter/chloramphenicol acetyl transferase reporter gene construct. In conclusion, the action of interleukins on both OTR mRNA expression and endometrial prostaglandin production alters around luteolysis. Pro-inflammatory interleukins suppress OTR expression in the late luteal phase, while LPS stimulates PGF(2alpha) without altering OTR mRNA expression. IL-I and -2 and LPS are therefore unlikely to initiate luteolysis but may cause raised production of PGF(2alpha) during uterine infection.

Stimuli and consequences of dendritic release of oxytocin within the brain

2007 ◽  
Vol 35 (5) ◽  
pp. 1252-1257 ◽  
Author(s):  
I.D. Neumann
Keyword(s):  
Paraventricular Nucleus ◽  
Stress Responses ◽  
Supraoptic Nucleus ◽  
Brain Regions ◽  
Model System ◽  
Intracerebral Microdialysis ◽  
Psychotherapeutic Intervention ◽  
Psychiatric Illnesses ◽  
Oxytocin Release ◽  
The Brain

The brain oxytocin system has served as a distinguished model system in neuroendocrinology to study detailed mechanisms of intracerebral release, in particular of somatodendritic release, and its behavioural and neuroendocrine consequences. It has been shown that oxytocin is released within various brain regions, but evidence for dendritic release is limited to the main sites of oxytocin synthesis, i.e. the hypothalamic SON (supraoptic nucleus) and PVN (paraventricular nucleus). In the present paper, stimuli of dendritic release of oxytocin and the related neuropeptide vasopressin are discussed, including parturition and suckling, i.e. the period of a highly activated brain oxytocin system. Also, exposure to various pharmacological, psychological or physical stressors triggers dendritic oxytocin release, as monitored by intracerebral microdialysis within the SON and PVN during ongoing behavioural testing. So far, dendritic release of the neuropeptide has only been demonstrated within the hypothalamus, but intracerebral oxytocin release has also been found within the central amygdala and the septum in response to various stimuli including stressor exposure. Such a locally released oxytocin modulates physiological and behavioural reproductive functions, emotionality and hormonal stress responses, as it exerts, for example, pro-social, anxiolytic and antistress actions within restricted brain regions. These discoveries make oxytocin a promising neuromodulator of the brain for psychotherapeutic intervention and treatment of numerous psychiatric illnesses, for example, anxiety-related diseases, social phobia, autism and postpartum depression.

scholarly journals Effect of mother alcoholization on the activity of ghrelin system in prenatal and early postnatal periods of rat offspring

2015 ◽  
Vol 13 (2) ◽  
pp. 10-13 ◽  
Author(s):  
Marat Igorevich Airapetov ◽  
Platon Platonovich Khokhlov ◽  
Eugeny Rudolfovich Bychkov ◽  
Edgar Arturovich Sekste ◽  
Natalia Dmitrievna Yakushina ◽  
...  
Keyword(s):  
Blood Serum ◽  
Mrna Expression ◽  
Brain Structures ◽  
Postnatal Period ◽  
Receptor Expression ◽  
Dopaminergic Receptors ◽  
Adult Rats ◽  
Ghrelin Receptor ◽  
Chronic Alcoholization ◽  
The Brain

The purpose of the paper was to study both the desacylghrelin (unacylated ghrelin) level in the blood serum and expression of mRNA ghrelin receptor in the brain structures in ontogeny after chronic alcoholization in rats. The results proved that the prenatal effect of ethanol negatively affected the maturation of dopaminergic and ghrelin systems of the brain as well as involvement of ghrelin system in mechanisms of alcohol dependence formation. The decrease of COMT mRNA expression simultaneoully with the increase of expression of D2 long and short isoforms of dopaminergic receptors and misbalance of ghrelin system were observed. Alcoholization of mothers reduced desacylghrelin level in the blood serum in early postnatal period in offsprings although mRNA expression of ghrelin receptor in the brain was elevated. Chronic alcoholization of adult rats also affected the ghrelin system. In the alcoholiztion process, the reduced contents of desacylghrelin in the blood serum with compensatory increase of ghrelin receptor expression in the brain were registered. After withdrawal of ethanol, the recovery of desacylghrelin level (tendency to normalization) was observed.

scholarly journals Social status in mouse social hierarchies is associated with variation in oxytocin and vasopressin 1a receptor densities

2019 ◽  
Author(s):  
Won Lee ◽  
Lisa C Hiura ◽  
Eilene Yang ◽  
Katherine A Broekman ◽  
Alexander G Ophir ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Social Status ◽  
Preoptic Area ◽  
Brain Regions ◽  
Lateral Septum ◽  
Receptor Expression ◽  
List Type ◽  
Social Hierarchies ◽  
Anterior Olfactory Nucleus ◽  
Vasopressin 1A Receptor

AbstractThe neuropeptides oxytocin and vasopressin and their receptors have established roles in the regulation of mammalian social behavior including parental care, sex, affiliation and pair-bonding, but less is known regarding their relationship to social dominance and subordination within social hierarchies. We have previously demonstrated that male mice can form stable linear dominance hierarchies with individuals occupying one of three classes of social status: alpha, subdominant, subordinate. Alpha males exhibit high levels of aggression and rarely receive aggression. Subdominant males exhibit aggression towards subordinate males but also receive aggression from more dominant individuals. Subordinate males rarely exhibit aggression and receive aggression from more dominant males. Here, we examined whether variation in social status was associated with levels of oxytocin (OTR) and vasopressin 1a (V1aR) receptor binding in socially relevant brain regions. We found that socially dominant males had significantly higher OTR binding in the nucleus accumbens core than subordinate animals. Alpha males also had higher OTR binding in the anterior olfactory nucleus, posterior part of the cortical amygdala and rostral lateral septum compared to more subordinate individuals. Conversely, alpha males had lower V1aR binding in the rostral lateral septum and lateral preoptic area compared to subordinates. These observed relationships have two potential explanations. Preexisting individual differences in the patterns of OTR and V1aR binding may underlie behavioral differences that promote or inhibit the acquisition of social status. More likely, the differential social environments experienced by dominant and subordinate animals may shift receptor expression, potentially facilitating the expression of adaptive social behaviors.HighlightsMice living in social hierarchies express different levels of oxytocin receptor (OTR) and vasopressin 1a receptor (V1aR) binding in various brain regions according to their social status.Alphas and subdominants have higher OTR binding in the nucleus accumbens compared to subordinates.Alphas have higher OTR binding in the anterior olfactory nucleus compared to subdominants and subordinates.Alphas have higher OTR and lower V1aR binding in the rostral lateral septum compared to subordinates.Alphas have lower V1aR binding in the lateral preoptic area compared to subordinates.

scholarly journals Effects of tiletamine-xylazine-tramadol combination and its specific antagonist on AMPK in the brain of rats

2019 ◽  
Vol 63 (2) ◽  
pp. 285-292
Author(s):  
Ning Ma ◽  
Xin Li ◽  
Hong-bin Wang ◽  
Li Gao ◽  
Jian-hua Xiao
Keyword(s):  
Mrna Expression ◽  
Opposite Effect ◽  
Brain Regions ◽  
Control Group ◽  
Sprague Dawley ◽  
Sd Rats ◽  
The Central Nervous System ◽  
Specific Antagonist ◽  
Sedation And Analgesia ◽  
The Brain

AbstractIntroduction:Tiletamine-xylazine-tramadol (XFM) has few side effects and can provide good sedation and analgesia. Adenosine 5’-monophosphate-activated protein kinase (AMPK) can attenuate trigeminal neuralgia. The study aimed to investigate the effects of XFM and its specific antagonist on AMPK in different regions of the brain.Material and Methods:A model of XFM in the rat was established. A total of 72 Sprague Dawley (SD) rats were randomly divided into three equally sized groups: XFM anaesthesia (M group), antagonist (W group), and XFM with antagonist interactive groups (MW group). Eighteen SD rats were in the control group and were injected intraperitoneally with saline (C group). The rats were sacrificed and the cerebral cortex, cerebellum, hippocampus, thalamus, and brain stem were immediately separated, in order to detect AMPKα mRNA expression by quantitative PCR.Results:XFM was able to increase the mRNA expression of AMPKα1 and AMPKα2 in all brain regions, and the antagonist caused the opposite effect, although the effects of XFM could not be completely reversed in some areas.Conclusion:XFM can influence the expression of AMPK in the central nervous system of the rat, which can provide a reference for the future development of anaesthetics for animals.

scholarly journals The Paraventricular Nucleus of the Thalamus as an Integrating and Relay Node in the Brain Anxiety Network

2021 ◽  
Vol 15 ◽  
Author(s):  
Gilbert J. Kirouac
Keyword(s):  
Paraventricular Nucleus ◽  
Relay Node ◽  
Central Nucleus ◽  
Social Avoidance ◽  
Bed Nucleus ◽  
Defensive Responses ◽  
Subcortical Regions ◽  
Cortical Regions ◽  
Experimental Findings ◽  
The Brain

The brain anxiety network is composed of a number of interconnected cortical regions that detect threats and execute appropriate defensive responses via projections to the shell of the nucleus accumbens (NAcSh), dorsolateral region of the bed nucleus of the stria terminalis (BSTDL) and lateral region of the central nucleus of the amygdala (CeL). The paraventricular nucleus of the thalamus (PVT) is anatomically positioned to integrate threat- and arousal-related signals from cortex and hypothalamus and then relay these signals to neural circuits in the NAcSh, BSTDL, and CeL that mediate defensive responses. This review describes the anatomical connections of the PVT that support the view that the PVT may be a critical node in the brain anxiety network. Experimental findings are reviewed showing that the arousal peptides orexins (hypocretins) act at the PVT to promote avoidance of potential threats especially following exposure of rats to a single episode of footshocks. Recent anatomical and experimental findings are discussed which show that neurons in the PVT provide divergent projections to subcortical regions that mediate defensive behaviors and that the projection to the NAcSh is critical for the enhanced social avoidance displayed in rats exposed to footshocks. A theoretical model is proposed for how the PVT integrates cortical and hypothalamic signals to modulate the behavioral responses associated with anxiety and other challenging situations.

scholarly journals Correlations Among mRNA Expression Levels of ATP7A, Serum Ceruloplasmin Levels, and Neuronal Metabolism in Unmedicated Major Depressive Disorder

2020 ◽  
Vol 23 (10) ◽  
pp. 642-652 ◽  
Author(s):  
Xuanjun Liu ◽  
Shuming Zhong ◽  
Lan Yan ◽  
Hui Zhao ◽  
Ying Wang ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Mrna Expression ◽  
Brain Regions ◽  
Regions Of Interest ◽  
Major Depressive ◽  
Expression Levels ◽  
Neuronal Metabolism ◽  
The Brain ◽  
Mrna Expression Levels

Abstract Background Previous studies have found that elevated copper levels induce oxidation, which correlates with the occurrence of major depressive disorder (MDD). However, the mechanism of abnormal cerebral metabolism of MDD patients remains ambiguous. The main function of the enzyme ATPase copper-transporting alpha (ATP7A) is to transport copper across the membrane to retain copper homeostasis, which is closely associated with the onset of mental disorders and cognitive impairment. However, less is known regarding the association of ATP7A expression in MDD patients. Methods A total of 31 MDD patients and 21 healthy controls were recruited in the present study. Proton magnetic resonance spectroscopy was used to assess the concentration levels of N-acetylaspartate, choline (Cho), and creatine (Cr) in brain regions of interest, including prefrontal white matter (PWM), anterior cingulate cortex (ACC), thalamus, lentiform nucleus, and cerebellum. The mRNA expression levels of ATP7A were measured using polymerase chain reaction (SYBR Green method). The correlations between mRNA expression levels of ATP7A and/or ceruloplasmin levels and neuronal biochemical metabolite ratio in the brain regions of interest were evaluated. Results The decline in the mRNA expression levels of ATP7A and the increase in ceruloplasmin levels exhibited a significant correlation in MDD patients. In addition, negative correlations were noted between the decline in mRNA expression levels of ATP7A and the increased Cho/Cr ratios of the left PWM, right PWM, and right ACC in MDD patients. A positive correlation between elevated ceruloplasmin levels and increased Cho/Cr ratio of the left PWM was noted in MDD patients. Conclusions The findings suggested that the decline in the mRNA expression levels of ATP7A and the elevated ceruloplasmin levels induced oxidation that led to the disturbance of neuronal metabolism in the brain, which played important roles in the pathophysiology of MDD. The decline in the mRNA expression levels of ATP7A and the elevated ceruloplasmin levels affected neuronal membrane metabolic impairment in the left PWM, right PWM, and right ACC of MDD patients.

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