Search NEL Online

Journal Article 2016; 37(1): 41-45 PubMed PMID: 26994384 Citation  Keywords:  Animals, Astrocytes:metabolism, Estrous Cycle:metabolism, Female, Glial Fibrillary Acidic Protein:metabolism, Immunohistochemistry, Oxytocin:metabolism, Rats, Rats, Sprague-Dawley, Supraoptic Nucleus:metabolism,.   

OBJECTIVE: Oxytocin (OXT) could facilitate preovulatory luteinizing hormone surge in animals and humans while brain OXT production depends on glial fibrillary acidic protein (GFAP)-associated astrocytic plasticity. Here, we examined if GFAP expressions in OXT-producing hypothalamic supraoptic nucleus (SON) correlate to special estrous stages.

METHODS: 38 adult female rats were classified into diestrus, proestrus, estrus, and metestrus groups determined by vaginal smear. Rats were decapitated and the SON was dissected for detecting Fos and GFAP levels by Western Blot and immunohistochemistry.

RESULTS: The result showed that Fos expression was significantly high at proestrus compared to other stages in Western blotting. No significant difference in total GFAP expression was observed between rats at different stages of the estrous cycle; however, at proestrus GFAP level at the dorsolateral portion of the SON (a region filled with OXT neurons) was significantly lower than that at the ventro-medial portion in immunohistochemistry.

CONCLUSION: There is a functional correlation between supraoptic neuron activity and proestrous OXT peak during estrous cycle; it is likely that a plastic change in GFAP expression in astrocytes selectively occurs around OXT neurons at proestrus and facilitates OXT release....

Read abstract  Full text PDF

Clinical Trial 2014; 35(6): 470-473 PubMed PMID: 25433841 Citation  Keywords:  Adolescent, Adult, Chemistry, Clinical:methods, Humans, Male, Oxytocin:blood, Perception:physiology, Reproducibility of Results, Saliva:metabolism, Young Adult,.   

OBJECTIVES: The neuroactive hormone oxytocin (OT) has significant influence on human behavior, and it has been measured peripherally in venous blood and in saliva in many behavioral neuroscience studies. Assessment of salivary hormone levels is popular due to non-invasiveness, but there is a controversy as to whether OT can be reliably measured in saliva and how possible time lags between plasma and salivary OT levels influence correlation.

DESIGN AND METHODS: In order to shed light on the question whether salivary and plasma OT levels correlate, we designed an experiment where healthy young men had to look at a presentation of trustworthy faces on a computer screen (faces were taken from an established database in trust research). During three points in time, plasma and saliva samples were collected and analyzed using ELISA.

RESULTS: Plasma and salivary OT levels did not correlate even when considering a time lag of 15 or 30 minutes.

CONCLUSIONS: Our results suggest that plasma and salivary OT levels do not correlate in healthy young men, and hence comparison of results across plasma and salivary studies is neither informative nor warranted. However, we recommend replicating this study based on mixed-gender samples....

Read abstract  Full text PDF

Journal Article 2014; 35(3): 213-217 PubMed PMID: 24977971 Citation  Keywords:  Adult, Aged, Child, Crime Victims:psychology, Female, Humans, Life Change Events, Male, Middle Aged, Oxytocin:blood, Stress, Psychological:blood, Suicide, Attempted:psychology, Violence:psychology, Young Adult,.   

OBJECTIVE: Some studies have reported an inverse relationship between childhood adversity and oxytocin levels. The purpose of this study was to assess the relationship between CSF and plasma oxytocin levels and lifetime trauma history in suicide attempters. We hypothesised lower CSF and plasma oxytocin levels in suicide attempters with high exposure to interpersonal violence and negative childhood emotional climate.

METHODS: 28 medication free suicide attempters participated in the study. CSF and plasma morning basal levels of oxytocin were assessed with specific radioimmunoassays. The Karolinska Interpersonal Violence Scale (KIVS) was used to elicit lifetime trauma history and revictimization status and the childhood emotional climate factor was derived from the socialization subscale of the Karolinska Scales of Personality.

RESULTS: Correlations between exposure to interpersonal violence as a child and as an adult and CSF and plasma oxytocin levels were not significant. Revictimized suicide attempters had significantly lower plasma oxytocin levels and more negative childhood emotional climate compared to non-revictimized suicide attempters.

CONCLUSIONS: Our results indicate a complex relationship between life time trauma and the oxytocin system....

Read abstract  Full text PDF

Journal Article 2012; 33(2): 124-132 PubMed PMID: 22592192 Citation  Keywords:  Animals, Gene Expression:physiology, Hypothalamo-Hypophyseal System:physiology, Male, Myocardium:cytology, Pituitary-Adrenal System:physiology, Protein Transport, Rats, Rats, Inbred Lew, Rats, Sprague-Dawley, Rats, Wistar, Receptors, Oxytocin:biosynthesis.   

OBJECTIVES: Cardiovascular system is regulated by a diverse array of hormones, neurotransmitters and neuropeptides. Oxytocin and its receptors (OTR) were also shown to regulate cardiovascular functions and this hormone was even called cardiovascular hormone. In recent publication, we demonstrated the expression of mRNA of OTR by real-time quantitative PCR (RT qPCR) in all rat heart compartments. The aim of this study was to investigate the effects of acute restraint stress on OTR mRNA expression in two rat strains with different activity of HPA axis.

METHODS: Adult male Sprague-Dawley and Lewis rats, the latter strain reported to have lower HPA activity, were used in RT qPCR studies and Wistar rats in immunofluorescent ones. Both acute restraint (IS) and this stress combined with the immersion of rats in water (ICS) lasted 60 min. Gene expression of OTR mRNA was estimated in all heart compartments after 1 or 3 hours after stress termination (IS1, IS3, ICS1, ICS3). The relative expression was calculated using 2(-ΔΔC)T method. In immunofluorescent studies we used commercial specific OTR antibodies.

RESULTS: In RT qPCR studies we found higher expression of OTR mRNA in atria than in ventricles and no statistical differences between Sprague-Dawley and Lewis rats under basal conditions. Relative expression of OTR mRNA after 60 min lasting stress exposure differed in dependence on the stress type and partly on the time interval after the stress termination. When compared to controls, in rat left atria both stressors caused inhibition of OTR mRNA expression in both rat strains. In rat ventricles, which have very low OTR mRNA expression, there was a significant difference in the effect of two stressors. In most groups ICS displayed the increase of OTR mRNA expression if compared to IS groups. Immunofluorescent studies revealed changes induced by acute restraint stress in all heart compartments. The immunofluorescent studies suggested that acute stress induces higher colocalization of OTR with the nuclei than it was observed in the controls.

CONCLUSIONS: The expression of OTR mRNA in all heart compartments of controls as well as after stress exposure in Sprague-Dawley and Lewis rats support the notion that OTR plays a regulatory role in the cardiovascular system and is also involved in the regulations in the heart after stress. The immunofluorescent observation that OTRs coexpress in areas of cell nuclei in certain heart compartments and after acute stress, compared to controls, requires further studies....

Read abstract  Full text PDF

Journal Article 2012; 33(1): 21-25 PubMed PMID: 22467107 Citation  Keywords:  Administration, Intranasal, Double-Blind Method, Humans, Oxytocin:administration & dosage, Saliva,.   

OBJECTIVE: This is the first study investigating whether levels of oxytocin in saliva remained elevated after intranasal oxytocin administration for the duration of an experiment (in which neurobehavioral effects of oxytocin were observed) taking more than two hours.

METHODS: Oxytocin levels were measured in saliva samples collected from 57 female participants right before (T0), approximately 1¼ h (T1), and approximately 2¼ h (T2) after intranasal administration of 16 IU of oxytocin or a placebo, using a double-blind, within-subjects design.

RESULTS: Average levels of oxytocin did not differ between conditions before use of the nasal spray, markedly increased only after oxytocin administration, and were still elevated after 2¼ h.

CONCLUSION: Salivary levels of oxytocin remained persistently elevated over the course of our experiment, i.e. for more than two hours after intranasal oxytocin administration and over a time-period in which neurobehavioral effects of oxytocin are commonly observed. This suggests that salivary concentrations may be a valuable biomarker for oxytocin, and may help to explain its effects on brain activity, information processing, and behavior....

Read abstract  Full text PDF

Journal Article 2011; 32(6): 805-810 PubMed PMID: 22286791 Citation  Keywords:  Animals, Hypothalamo-Hypophyseal System:physiology, Male, Myocardium:cytology, Oxytocin:metabolism, Pituitary-Adrenal System:physiology, RNA, Messenger:metabolism, Rats, Rats, Inbred Lew, Rats, Sprague-Dawley, Receptors, Oxytocin:genetics,.   

OBJECTIVES: Oxytocin (OT) is a neuropeptide acting both as a peripheral hormone and in the brain as neurotransmitter and neuromodulator. In addition to its well-known effects on milk-ejection and uterine contraction, OT was shown to exert neuroendocrine regulation of heart functions. The aim of this study was to investigate the expression of mRNA of OT receptors (OTR) in rat hearts by real-time quantitative PCR (qPCR). The study was performed in Sprague-Dawley (SD) and Lewis (LE) rat strains, the latter having lower activity of HPA axis.

METHODS: We used adult male SD and LE rats. OTR mRNA expression was detected in all heart chambers by comparing their threshold cycle values (CT) to CT of reference gene β-actin. The relative expression ratios were calculated using the 2-ΔΔCT method. The specificity of reaction of primary antibody with OTRs was tested by Western Blot and localization of OTR in the heart compartments was performed by immunofluorescence with commercial OTR specific antibodies.

RESULTS: We found expression of OTR mRNA in all heart compartments. The expression of OTR mRNA in both atria (LA, RA) was much higher than in the ventricles (RV, LV). By using two-way ANOVA we found no statistical differences between corresponding compartments of SD and LE rats. Immunohistochemical studies showed that OTR staining is not related to neuronal tissue and findings from left atrium indicate that prevalent localization of OTR is on cell membranes of cardiomyocytes.

CONCLUSIONS: The finding of expression of OTR mRNA by real-time qPCR and proof of OTR staining by immunohistochemistry in all heart compartments indicate that OT and its receptors may have function as a cardiovascular hormone. The differences in the HPA axis activity, as is exemplified in Sprague-Dawley and Lewis rat strain, do not project in the expression of OTR mRNA under basal condition. The effect of activity of HPA on OTR expression should be studied under stimulated conditions as it was performed in the behavioral studies....

Read abstract  Full text PDF

Journal Article 2009; 30(3): 335-342 PubMed PMID: 19855356 Citation  Keywords:  Analysis of Variance, Animals, Behavior, Animal:drug effects, Bornanes:pharmacology, Dose-Response Relationship, Drug, Grooming:drug effects, Hormone Antagonists:pharmacology, Male, Motor Activity:drug effects, Oxytocics:administration & dosage, Oxytocin:.   

OBJECTIVES: Oxytocin (OXY) in addition to peripheral actions has many central regulatory functions which can be studied on animal models. In the present study we examined in rats, which behavioral actions of OXY and long-acting carba-analog of OXY carbetocin (CBT) in the open-field can be inhibited by OXY-receptor antagonists. Our interest focused on the behavioral patterns considered indicative of anxiety-related behavior. To determine what is the participation of OXY receptor on OXY and CBT induced behavioral changes, we used two peptide and one nonpeptide OXY antagonists differing in selectivity for OXY receptor.

METHODS: OXY, CBT as well as OXY antagonists were injected intraperitoneally, and spontaneous behavior (horizontal and vertical activity, grooming) of Wistar rats was observed in the circular open-field arena 60 min after application of drugs; in some experiments testing was performed without treatment few days after drug administration.

RESULTS: OXY at the dose 0.05 mg/kg increased locomotion indicating anxiety attenuation, but 1.0 mg/kg reduced both locomotion and rearing. CBT in the dose range 0.1-3.0 mg/kg either did not change or increased horizontal activity. The increase in exploration after both peptides persisted for several days. A marked difference in the behavioral effects of the two peptides was grooming enhancement induced by OXY compared with the absence of this effect after CBT. The increase of the activity induced by OXY and CBT indicating anxiolytic-like action was blocked by OXY antagonists. However, the reduction of exploration induced by 1.0 mg dose of OXY was only partially reversed. The OXY induced enhanced grooming was completely antagonized by all used antagonists.

CONCLUSIONS: Behavioral effects of OXY and its antagonists after their i.p. application indicate that they penetrate blood brain barrier. The diversity in potency of OXY antagonists to inhibit grooming and other behaviors induced by OXY suggests that receptors participating in these behaviors may differ in brain localization, receptor conformation and/or in the utilized signaling pathways....

Read abstract  Full text PDF

Journal Article 2008; 29(4): 547-551 PubMed PMID: 18766146 Citation  Keywords:  Animals, Female, Male, Neuronal Plasticity:physiology, Neurons:cytology, Oxytocin:metabolism, Paraventricular Hypothalamic Nucleus:cytology, Rats, Restraint, Physical, Rodentia, Stress, Psychological,.   

OBJECTIVES AND METHODS: The presence of oxytocin (OT) and its putative participation to the phenotypic plasticity of CRH neurones in the stressed jerboa was investigated. We analysed by immunocytochemistry the OT expression within the hypothalamic parvicellular paraventricular nucleus (pPVN) of male jerboas submitted to an acute immobilization (30 min).

RESULTS: OT presence was clearly demonstrated in the pPVN of the jerboa and no significant difference in the number of OT immunolabeled cells was observed whatever the experimental conditions. Interestingly, CRH-immunoreactive neurons coexpressed OT within cell bodies and terminals in a similar way both in control and stressed animals. The level of coexpression was regionally heterogeneous and was not sensitive to the stress immobilization.

CONCLUSION: The present data reveal for the first time the occurrence of OT in hypothalamic pPVN neurons of the jerboa. Moreover, this OT expression level does not change upon an acute immobilization stress. These new data, coupled together with our previous work in the jerboa, incontestably establish a clear dichotomy between a stress-responsive CRH/CCK system and a stress non-responsive OT/VP system in the pPVN....

Read abstract  Full text PDF