Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although active learning works, promoting it in large undergraduate science classes is difficult. Here, three students (F. Naji, L. Salci, and G. Hoit) join their teacher (P. K. Rangachari) in describing one such attempt. Two cohorts in a first-year undergraduate biology course explored the molecular underpinnings of human misbehavior. Students were divided into 18 groups and randomly allotted to deal with one of the four deadly sins: sloth, gluttony, lust, and wrath. Students were expected to read primary sources to devise molecular ways to counter these sins. Group progress was monitored over the 12-wk period by the preceptor (P. K. Rangachari) at scheduled intervals. A single randomly selected student was questioned about the work done, and future directions were provided by the preceptor. At the end of the term, randomly selected students defended their group's approaches to the entire class. A final written report was graded. The following multiple target molecules were considered for each sin: gluttony (cholecystokinin, ghrelin, GABA, leptin, peptide YY, neuropeptide Y, and the melanocortin 4 receptor); sloth (dopamine, glutamate, GABA, and orexin); wrath (serotonin, GABA, glutamate, and corticotropin-releasing hormone receptor 2); and lust (prolactin, testosterone, oxytocin, dopamine, and estrogen). Students noted that the project provided a valuable learning experience, and the random selection approach gave students a greater sense of responsibility to their group. The project helped students hone their skills at searching, synthesizing, sharing, and presenting information, fostered group interactions, and provided a solid knowledge base for subsequent courses.
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PMID:The UNSIN project: exploring the molecular physiology of sins. 2238 7

Single-minded 1 (Sim1) is a transcription factor necessary for development of the paraventricular nucleus of the hypothalamus (PVH). This nucleus is a critical regulator of appetite, energy expenditure and body weight. Previously we showed that Sim1(+/-) mice and conditional postnatal Sim1(-/-) mice exhibit hyperphagia, obesity, increased linear growth and susceptibility to diet-induced obesity, but no decrease in energy expenditure. Bilateral ablation of the PVH causes obesity due to hyperphagia and reduced energy expenditure. It remains unknown whether Sim1 neurons regulate energy expenditure. In this study, Sim1cre mice were bred to homozygous inducible diphtheria toxin receptor (iDTR) mice to generate mice expressing the simian DTR in Sim1 cells. In these mice, Sim1 neuron ablation was performed by intracerebroventricular (ICV) injection of diphtheria toxin. Compared to controls, mice with Sim1 neuron ablation became obese (with increased fat mass) on a chow diet due to increased food intake and reduced energy expenditure. In post-injection mice, we observed a strong inverse correlation between the degree of obesity and hypothalamic Sim1 expression. The reduction in baseline energy expenditure observed in these mice was accompanied by a reduction in activity. This reduction in activity did not fully account for the reduced energy expenditure as these mice exhibited decreased resting energy expenditure, decreased body temperature, decreased brown adipose tissue temperature, and decreased UCP1 expression suggesting an impairment of thermogenesis. In injected mice, hypothalamic gene expression of Sim1, oxytocin (OXT) and thyrotropin releasing hormone (TRH) was reduced by about 50%. These results demonstrate that Sim1 neurons in adult mice regulate both food intake and energy expenditure. Based on the body of work in the field, feeding regulation by Sim1 neurons likely occurs in both the PVH and medial amygdala, in contrast to energy expenditure regulation by Sim1 neurons, which likely is localized to the PVH.
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PMID:Ablation of Sim1 neurons causes obesity through hyperphagia and reduced energy expenditure. 2255 67

Hunger is a complex behavioural state that elicits intense food seeking and consumption. These behaviours are rapidly recapitulated by activation of starvation-sensitive AGRP neurons, which present an entry point for reverse-engineering neural circuits for hunger. Here we mapped synaptic interactions of AGRP neurons with multiple cell populations in mice and probed the contribution of these distinct circuits to feeding behaviour using optogenetic and pharmacogenetic techniques. An inhibitory circuit with paraventricular hypothalamus (PVH) neurons substantially accounted for acute AGRP neuron-evoked eating, whereas two other prominent circuits were insufficient. Within the PVH, we found that AGRP neurons target and inhibit oxytocin neurons, a small population that is selectively lost in Prader-Willi syndrome, a condition involving insatiable hunger. By developing strategies for evaluating molecularly defined circuits, we show that AGRP neuron suppression of oxytocin neurons is critical for evoked feeding. These experiments reveal a new neural circuit that regulates hunger state and pathways associated with overeating disorders.
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PMID:Deconstruction of a neural circuit for hunger. 2280 96

MAGED1, NECDIN and MAGEL2 are members of the MAGE gene family. The latter two of these genes have been involved in Prader-Willi syndrome (PWS), which includes hyperphagia, repetitive and compulsive behaviors, and cognitive impairment. Here, we show that Maged1-deficient mice develop progressive obesity associated with hyperphagia and reduced motor activity. Loss of Maged1 also results in a complex behavioral syndrome that includes reduced social interactions and memory, deficient sexual behavior, as well as increased anxiety and self-grooming. Oxytocin (OT), which is produced in the hypothalamus, can act as a neurotransmitter that reduces anxiety, promotes social behaviors and regulates food intake. Growing evidences indicate that OT is involved in autism. We found that Maged1 mutants showed a severe reduction in the levels of mature OT, but not of its precursors, in the hypothalamus. Moreover, the administration of OT rescued the deficit in social memory of these mice. We conclude that Maged1 is required for OT processing or stability. A decrease in mature OT levels in Maged1 mutants affects social interactions and possibly other behavioral processes. Our observations suggest that, in human, MAGED1 could play a role in autism or cause a neurodevelopmental condition that is reminiscent of the PWS.
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PMID:Loss of Maged1 results in obesity, deficits of social interactions, impaired sexual behavior and severe alteration of mature oxytocin production in the hypothalamus. 2286 74

Leptin is an adipocyte-derived hormone that controls energy balance by acting primarily in the CNS, but its action is lost in common forms of obesity due to central leptin resistance. One potential mechanism for such leptin resistance is an increased hypothalamic expression of Suppressor of cytokine signaling 3 (Socs3), a feedback inhibitor of the Jak-Stat pathway that prevents Stat3 activation. Ample studies have confirmed the important role of Socs3 in leptin resistance and obesity. However, the degree to which Socs3 participates in the regulation of energy homeostasis in nonobese conditions remains largely undetermined. In this study, using adult mice maintained under standard diet, we demonstrate that Socs3 deficiency in the mediobasal hypothalamus (MBH) reduces food intake, protects against body weight gain, and limits adiposity, suggesting that Socs3 is necessary for normal body weight maintenance. Mechanistically, MBH Socs3-deficient mice display increased hindbrain sensitivity to endogenous, meal-related satiety signals, mediated by oxytocin signaling. Thus, oxytocin signaling likely mediates the effect of hypothalamic leptin on satiety circuits of the caudal brainstem. This provides an anatomical substrate for the effect of leptin on meal size, and more generally, a mechanism for how the brain controls short-term food intake as a function of the energetic stores available in the organism to maintain energy homeostasis. Any dysfunction in this pathway could potentially lead to overeating and obesity.
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PMID:Inactivation of Socs3 in the hypothalamus enhances the hindbrain response to endogenous satiety signals via oxytocin signaling. 2319 3

This study analyzed the effects of systemic oxytocin (OT) administration and 48-h food deprivation on the polydipsia, hyperphagia, and polyuria produced by electrolytic lesions of the mediobasal hypothalamus (MBH). In a first experiment, food deprivation transiently decreased the polydipsic response, whereas food deprivation plus OT administration reduced the water intake and urine excretion of polydipsic animals but not their subsequent food intake. These results were replicated in a second experiment (20 days), which also showed that OT potentiates sodium excretion, reducing the estimated plasma sodium levels in food-deprived MBH-lesioned animals. Administration of OT on day 21 to food-deprived (from day 20 to 22) animals (second period of the experiment 2) blocked the differences in water intake and urine excretion volumes between MBH and control animals on days 21 and 22. Subsequently, this 48-h food deprivation induced an additional and lasting (days 23-40) reduction in the intake of water and food of MBH animals. According to these findings, OT administration and/or food deprivation may potentially exert enduring reducing effects on the polydipsia, polyuria, and hyperphagia of MBH syndrome.
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PMID:Differential lasting inhibitory effects of oxytocin and food-deprivation on mediobasal hypothalamic polydipsia. 2345 95

Antagonism of oxytocin (OT) receptors (OTRs) impairs the formation of pair bonds in prairie voles (Microtus ochrogaster) and zebra finches (Taenioypygia guttata), and also reduces the preference for the larger of two groups ("gregariousness") in finches. These effects tend to be stronger in females. The contributions of specific peptide cell groups to these processes remain unknown, however. This issue is complicated by the fact that OTRs in finches and voles bind not only forms of OT, but also vasopressin (VP), and >10 cell groups produce each peptide in any given species. Using RNA interference, we found that knockdown of VP and OT production in the paraventricular nucleus of the hypothalamus exerts diverse behavioral effects in zebra finches, most of which are sexually differentiated. Our data show that knockdown of VP production significantly reduces gregariousness in both sexes and exerts sex-specific effects on aggression directed toward opposite-sex birds (increases in males; decreases in females), whereas OT knockdown produces female-specific deficits in gregariousness, pair bonding, and nest cup ownership; reduces side-by-side perching in both sexes; modulates stress coping; and induces hyperphagia in males. These findings demonstrate that paraventricular neurons are major contributors to the effects of VP-OT peptides on pair bonding and gregariousness; reveal previously unknown effects of sex-specific peptide on opposite-sex aggression; and demonstrate a surprising lack of effects on same-sex aggression. Finally, the observed effects of OT knockdown on feeding and stress coping parallel findings in mammals, suggesting that OT modulation of these processes is evolutionarily conserved across the amniote vertebrate classes.
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PMID:Hypothalamic oxytocin and vasopressin neurons exert sex-specific effects on pair bonding, gregariousness, and aggression in finches. 2471 11

Individuals with Prader-Willi syndrome (PWS) have a significant reduction in the number of oxytocin-producing neurons (42%) in the hypothalamic paraventricular nucleus. A number of animal studies and observations of humans show that lesions in this region can produce PWS-like symptoms. Given the evidence for potential oxytocin deficiency, we tested the effects of a course of intranasal oxytocin on PWS symptoms. Thirty individuals with PWS aged 12-30 years participated in an 18-week randomized double-blind placebo-controlled crossover trial. Participants received 8 weeks of oxytocin and 8 weeks of placebo with a minimum 2-week washout period. The first 11 participants received the following oxytocin doses: 24 IU (twice daily) B.I.D for participants 16 years and over and 18 IU B.I.D for participants 13-15 years. The dose was increased for the remaining 18 participants to 40 IU B.I.D for participants 16 years and over and 32 IU B.I.D for 13-15 years. Measures used to assess changes were standardized well-accepted measures, including the Developmental Behavior Checklist-Monitor, Parent, Teacher, and Adult; The Yale-Brown Obsessive Compulsive Scale; The Dykens Hyperphagia questionnaire; Reading The Mind in the Eyes Test; Epworth Sleepiness Scale and the Movie Stills. Oxytocin had little impact on any measure. The only significant difference found between the baseline, oxytocin, and placebo measures was an increase in temper outbursts (P = 0.023) with higher dose oxytocin. The lack of effect of oxytocin nasal spray may reflect the importance of endogenous release of oxytocin in response to exogenous oxytocin.
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PMID:A double-blind randomized controlled trial of oxytocin nasal spray in Prader Willi syndrome. 2498 Jun 12

Activation of melanocortin-4 receptors (MC4Rs) restrains feeding and prevents obesity; however, the identity, location, and axonal projections of the neurons bearing MC4Rs that control feeding remain unknown. Reexpression of MC4Rs on single-minded 1 (SIM1)(+) neurons in mice otherwise lacking MC4Rs is sufficient to abolish hyperphagia. Thus, MC4Rs on SIM1(+) neurons, possibly in the paraventricular hypothalamus (PVH) and/or amygdala, regulate food intake. It is unknown, however, whether they are also necessary, a distinction required for excluding redundant sites of action. Hence, the location and nature of obesity-preventing MC4R-expressing neurons are unknown. Here, by deleting and reexpressing MC4Rs from cre-expressing neurons, establishing both necessity and sufficiency, we demonstrate that the MC4R-expressing neurons regulating feeding are SIM1(+), located in the PVH, glutamatergic and not GABAergic, and do not express oxytocin, corticotropin-releasing hormone, vasopressin, or prodynorphin. Importantly, these excitatory MC4R-expressing PVH neurons are synaptically connected to neurons in the parabrachial nucleus, which relays visceral information to the forebrain. This suggests a basis for the feeding-regulating effects of MC4Rs.
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PMID:MC4R-expressing glutamatergic neurons in the paraventricular hypothalamus regulate feeding and are synaptically connected to the parabrachial nucleus. 2515 44

Oxytocin (Oxt), a neuropeptide produced in the hypothalamus, is implicated in regulation of feeding. Recent studies have shown that peripheral administration of Oxt suppresses feeding and, when infused subchronically, ameliorates hyperphagic obesity. However, the route through which peripheral Oxt informs the brain is obscure. This study aimed to explore whether vagal afferents mediate the sensing and anorexigenic effect of peripherally injected Oxt in mice. Intraperitoneal Oxt injection suppressed food intake and increased c-Fos expression in nucleus tractus solitarius to which vagal afferents project. The Oxt-induced feeding suppression and c-Fos expression in nucleus tractus solitarius were blunted in mice whose vagal afferent nerves were blocked by subdiaphragmatic vagotomy or capsaicin treatment. Oxt induced membrane depolarization and increases in cytosolic Ca(2+) concentration ([Ca(2+)]i) in single vagal afferent neurons. The Oxt-induced [Ca(2+)]i increases were markedly suppressed by Oxt receptor antagonist. These Oxt-responsive neurons also responded to cholecystokinin-8 and contained cocaine- and amphetamine-regulated transcript. In obese diabetic db/db mice, leptin failed to increase, but Oxt increased [Ca(2+)]i in vagal afferent neurons, and single or subchronic infusion of Oxt decreased food intake and body weight gain. These results demonstrate that peripheral Oxt injection suppresses food intake by activating vagal afferent neurons and thereby ameliorates obesity in leptin-resistant db/db mice. The peripheral Oxt-regulated vagal afferent neuron provides a novel target for treating hyperphagia and obesity.
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PMID:Peripheral oxytocin activates vagal afferent neurons to suppress feeding in normal and leptin-resistant mice: a route for ameliorating hyperphagia and obesity. 2554 Jan 1


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