Exposure to chronic isolation modulates receptors mRNAs for oxytocin and vasopressin in the hypothalamus and heart.

The goal of our study was to explore the effect of social isolation stress of varying durations on the plasma oxytocin (OT), messenger ribonucleic acid (mRNA) for oxytocin receptor (OTR), plasma arginine vasopressin (AVP) and mRNA for V1a receptor of AVP (V1aR) expression in the hypothalamus and heart of socially monogamous female and male prairie voles (Microtus ochrogaster). Continuous isolation for 4 weeks (chronic isolation) increased plasma OT level in females, but not in males. One hour of isolation every day for 4 weeks (repeated isolation) was followed by a significant increase in plasma AVP level. Chronic isolation, but not repeated isolation, significantly decreased OTR mRNA in the hypothalamus and heart in both sexes. Chronic isolation significantly decreased cardiac V1aR mRNA, but no effect on hypothalamic V1aR mRNA expression. We did not find a gender difference within repeated social isolation groups. The results of the present study reveal that although chronic social isolation can down-regulate gene expression for the OTR in both sexes, the release of the OT peptide was increased after chronic isolation only in females, possibly somewhat protecting females from the negative consequences of isolation. In both sexes repeated, but not chronic, isolation increased plasma AVP, which could be permissive for mobilization and thus adaptive in response to a repeated stressor. The differential effects of isolation on OT and AVP systems may help in understanding mechanisms through social interactions can be protective against emotional and cardiovascular disorders.

Effects of social isolation on mRNA expression for corticotrophin-releasing hormone receptors in prairie voles.

Previous studies have demonstrated that various type of stressors modulate messenger ribonucleic acid (mRNA) for type 1 corticotropin-releasing hormone (CRH) receptor (CRH-R1 mRNA) and type 2 CRH receptor (CRH-R2 mRNA). The purpose of this study was to explore the effect of social isolation stress of varying durations on the CRH, CRH-R1 and CRH-R2 mRNAs expression in the hypothalamus, hippocampus and pituitary of socially monogamous female and male prairie voles (Microtus ochrogaster). Isolation for 1h (single isolation) or 1h of isolation every day for 4 weeks (repeated isolation) was followed by a significant increase in plasma corticosterone levels. Single or repeated isolation increased hypothalamic CRH mRNA expression, but no changes in CRH-R1 mRNA in the hypothalamus were observed. Continuous isolation for 4 weeks (chronic isolation) showed no effect on hypothalamic CRH or CRH-R1 mRNAs in female or male animals. However, hypothalamic CRH-R2 mRNA was significantly reduced in voles exposed to chronic isolation. Single or repeated isolation, but not chronic isolation, significantly increased CRH-R1 mRNA and decreased CRH-R2 mRNA in the pituitary. Despite elevated CRH mRNA expression, CRH-R1 and CRH-R2 mRNAs were not modulated in the hippocampus following single or repeated isolation. Although, chronic isolation did not affect hippocampal CRH or CRH-R1 mRNAs, it did increase CRH-R2 mRNA expression in females and males. The results of the present study in prairie voles suggest that social isolation has receptor subtype and species-specific consequences for the modulation of gene expression for CRH and its receptors in brain and pituitary. Previous studies have revealed a female-biased increase in oxytocin in response to chronic isolation; however, we did not find a sex difference in CRH or its receptors following single, repeated or chronic social isolation, suggesting that sexually dimorphic processes beyond the CRH system, possibly involving vasopressin, might explain this difference.

Social isolation modulates corticotropin-releasing factor type 2 receptor, urocortin 1 and urocortin 2 mRNAs expression in the cardiovascular system of prairie voles.

The purpose of the present study was to examine the effect of social isolation stress on the expression of messengers ribonucleic acid (mRNAs) for corticotropin-releasing factor receptor type 2 (CRF2 receptor), urocortin 1 (Ucn 1) and urocortin 2 (Ucn 2) in the cardiovascular system of female and male prairie voles (Microtus ochrogaster). Isolation for 1 h (single isolation) or 1 h of isolation every day for 4 weeks (repeated isolation) was followed by a marked increase in plasma corticosterone level. However, continuous isolation for 4 weeks (chronic isolation) did not significantly affect plasma corticosterone level in female or male animals. A single period of isolation did not influence the expression of the CRF2 receptor, however, both repeated and chronic isolation significantly decreased CRF2 receptor mRNA in the ventricle and aorta of both sexes. Neither single nor chronic isolation significantly affected Ucn 1 mRNAs expression; however, repeated isolation increased Ucn 1 mRNA expression in the ventricles of female and male animals. Although, a single isolation produced no effect on cardiac Ucn 2 mRNA expression, both repeated and chronic isolation were followed by increased heart Ucn 2 mRNA expression in both sexes. We speculate that during repeated isolation Ucn 1 along with Ucn 2 are increased, which in turn down-regulates CRF2 receptor mRNA expression, and that Ucn 2 also may be one of factors responsible for the down-regulation of CRF2 receptor mRNA expression in cardiovascular system that is associated with chronic isolation.

Stress differentially modulates mRNA expression for corticotrophin-releasing hormone receptors in hypothalamus, hippocampus and pituitary of prairie voles.

This study compares the effect of an acute stressor (restraint for 1h) versus a chronic stressor (social isolation for 4 weeks) on the expression of mRNAs for corticotropin-releasing hormone (CRH), CRH receptor type 1 (CRH-R1) and type 2 (CRH-R2) in the hypothalamus, hippocampus and pituitary of socially monogamous female prairie voles (Microtus ochrogaster). Animals were studied immediately following a stressor or as a function of repairing with a familiar sibling. Despite elevated expression of CRH mRNA, no alteration of CRH-R1 mRNA in the hypothalamus was observed following restraint stress or 4 weeks of social isolation. Hypothalamic CRH-R2 mRNA was significantly lower in voles exposed to restraint or isolation. CRH-R2 mRNA also remained down-regulated in isolated animals when these animals were re-paired with their sibling for one day following 28 days of isolation. Restraint, but not isolation, significantly increased CRH-R1 mRNA and decreased CRH-R2 mRNA in the pituitary. However, these differences were no longer observed when these animals were re-paired with their sibling for one day. Despite elevated CRH mRNA expression, CRH-R1 mRNA did not increase in the hippocampus following restraint or social isolation. Social isolation, but not restraint stress, increased CRH-R2 mRNA in the hippocampus, when these animals were re-paired with their sibling for one day the modulation of CRH mRNA remained up-regulated. Plasma corticosterone was elevated only following restraint, and not in animals that were handled, isolated or re-paired. The results of the present study reveal that acute restraint as well as social isolation can have significant consequences for the modulation of gene expression for the CRH receptors in brain and pituitary of prairie voles.

Modulation of cardiac oxytocin receptor and estrogen receptor alpha mRNAs expression following neonatal oxytocin treatment.

Oxytocin (OT) is known for its role in reproduction. However, evidence has emerged suggesting its involvement in the regulation of the cardiovascular system. Here we examine the hypothesis that neonatal exposure to OT can have both short-term and long-lasting consequences on gene expression in heart tissue. On the first day of postnatal life, female and male prairie voles (Microtus ochrogaster) were randomly assigned to receive one of following treatments: 50 microl i.p. injection of (a) 3 microg OT (b) 0.3 microg of OT antagonist (OTA), or (c) isotonic saline (SAL). Hearts were collected on postnatal day 1 (D1, 2 h after injection), day 8 (D8), or day 21 (D21), and the mRNA expression for OT receptor (OTR), estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta as a function of age, treatment, and sex were measured using RT-PCR. Neonatal treatment with OT showed a marked increase in cardiac OTR mRNA expression on postnatal D1, but not D8 or D21, in both female and male animals. ERalpha increased as a function of OT treatment only in females. Although significant treatment effects were no longer detected in D8 or D21 animals, there were significant changes in the relative expression of all types of mRNA between D1 and D21 with age-related declines in OTR and ERbeta and increases in ERalpha Neonatal treatment with OTA showed no changes in cardiac OTR, ERalpha, or ERbeta mRNAs expression. The results indicate that during the early postnatal period OT can have rapid effects on the expression of OTR and ERalpha mRNAs and that these effects are mitigated by D8 or D21. Also, with the exception of ERalpha mRNA, the effects are the same in both sexes.

Neonatal oxytocin treatment modulates oxytocin receptor, atrial natriuretic peptide, nitric oxide synthase and estrogen receptor mRNAs expression in rat heart.

Oxytocin (OT) has been implicated in reproductive functions, induction of maternal behavior as well as endocrine and neuroendocrine regulation of the cardiovascular system. Here we demonstrate that neonatal manipulation of OT can modulate the mRNAs expression for OT receptor (OTR), atrial natriuretic peptide (ANP), endothelial nitric oxide synthase (eNOS) and estrogen receptor alpha (ERalpha) in the heart. On the first day of postnatal life, female and male rats were randomly assigned to receive one of the following treatments: (a) 50microl i.p. injection of 7microg OT; (b) 0.7microg of OT antagonist (OTA); or (c) isotonic saline (SAL). Hearts were collected either on postnatal day 1 or day 21 (D1 or D21) and the mRNAs expression of OTR, ANP, inducible NOS (iNOS), eNOS, ERalpha and estrogen receptor beta (ERbeta) were compared by age, treatment, and sex utilizing real time PCR. OT treatment significantly increased heart OTR, ANP and eNOS mRNAs expression on D1 in both males and females, ERalpha increased only in females. While there were significant changes in the relative expression of all types of mRNA between D1 and D21, there were no significant treatment effects observed in D21 animals. OTA treatment significantly decreased basal ANP and eNOS mRNAs expression on D1 in both sexes. The results indicate that during the early postnatal period OT can have an immediate effect on the expression OTR, ANP, eNOS, and ERalpha mRNAs and that these effects are mitigated by D21. Also with the exception of ERalpha mRNA, the effects are the same in both sexes.

Modulation of corticotropin-releasing hormone type 2 receptor and urocortin 1 and urocortin 2 mRNA expression in the cardiovascular system of prairie voles following acute or chronic stress.

The purpose of this study was to compare the effects of an acute stressor (restraint) versus a chronic stressor (social isolation) on the expression of mRNAs for corticotropin-releasing hormone receptor type 2 (CRH-R2) and urocortin 1 (Ucn 1) and urocortin 2 (Ucn 2) in the cardiovascular system of socially monogamous prairie voles of both sexes. Acute restraint for 1 h was followed by a marked increase in plasma corticosterone, and when the animals were re-paired for 1 day, the increment of corticosterone was normalized. However, following chronic social isolation for 4 weeks, plasma corticosterone did not differ significantly from the levels measured in animals living in pairs. Restraint or isolation significantly decreased CRH-R2 mRNA in ventricle, atria, and aorta; however, when these animals were re-paired for 1 day, the modulation of CRH-R2 mRNA was normalized in restraint but not in isolated animals. Restraint stress increased the Ucn 1 mRNA expression in the heart of female and male prairie voles, and when the animals were re-paired, the modulation of Ucn 1 mRNA expression was normalized. However, chronic isolation showed no effect on cardiac Ucn 1 mRNA expression. Although acute restraint stress produced no effect on the cardiac Ucn 2 mRNA expression, chronic isolation was followed by an increased heart Ucn 2 mRNA expression in both sexes. When the isolated animals were re-paired for 1 day, the cardiac Ucn 2 mRNA expression remained upregulated. The results of the present study reveal that acute restraint as well as social isolation can have significant consequences for the modulation of gene expression for the CRH-R2 and the urocortin peptides in cardiovascular tissue in female and male prairie voles.

A new dipeptide, O-phosphoserylethanolamine isolated from Agkistroden blomhoffi (mamushi).

A new dipeptide was isolated from several tissues of Agkistroden blomhoffi (mamushi: a venomous snake in Japan), using ion-exchange resins and thin-layer chromatography. It was identified as O-phosphoserylethanolamine by mass spectrometry and comparison with synthetic compounds using several methods. This compound was contained in several mamushi tissues including the liver, heart, brain, bile, and muscle. The concentrations of O-phosphoserylethanolamine in the liver, brain, muscle, skin, heart, and bile were 7.17+/-3.11,16.98+/-4.25,37.37+/-7.88,37.56+/-8.97,23.93+/-6.11, and 22.21+/-5.76 micromol/g, respectively.