Mitochondria, Oxytocin, and Vasopressin: Unfolding the Inflammatory Protein Response.
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ABSTRACT:
SUBMITTER: Bordt EA
PROVIDER: S-EPMC7416501 | biostudies-literature | 2019 Aug
REPOSITORIES: biostudies-literature
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Project description:Neuropeptidergic signaling is widely adopted by animals for the regulation of physiology and behavior in a rapidly changing environment. The vasopressin/oxytocin neuropeptide family originates from an ancestral peptide precursor in the antecedent of protostomian and deuterostomian animals. In vertebrates, vasopressin and oxytocin have both hormonal effects on peripheral target tissues, such as in the regulation of reproduction and water balance, and neuromodulatory actions in the central nervous system controlling social behavior and cognition. The recent identification of vasopressin/oxytocin-related signaling in C. elegans reveals that this peptidergic system is widespread among nematodes. Genetic analysis of the C. elegans nematocin system denotes vasopressin/oxytocin-like peptides as ancient neuromodulators of neuronal circuits involved in reproductive behavior and associative learning, whereas former invertebrate studies focused on conserved peripheral actions of this peptide family. Nematocin provides neuromodulatory input into the gustatory plasticity circuit as well as into distinct male mating circuits to generate a coherent mating behavior. Molecular interactions are comparable to those underlying vasopressin- and oxytocin-mediated effects in the mammalian brain. Understanding how the vasopressin/oxytocin family fine-tunes neuronal circuits for social behavior, learning and memory poses a major challenge. Functional conservation of these effects in nematodes and most likely in other invertebrates enables the development of future models to help answering this question.
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Project description:Over the past few years there has been an increased interest in cannabidiol (CBD) for general use as well as alternative therapeutic for various diseases. Although CBD has only been FDA approved for seizures under the oral formulation, Epidiolex®, the public has used various unregulated forms of CBD to treat a variety of ailments from pain to anxiety and insomnia. Moreover, an increasing subset of CBD advocates take CBD daily to prevent inflammation. This expanded use of CBD strongly suggests that more research is necessary to elucidate the safety and efficacy of CBD and determine the mechanisms by which it acts. Thus, we conducted two separate studies. In the first, RNA sequencing (RNA-Seq) analysis of brains of female mice undergoing experimental autoimmune encephalomyelitis (EAE) in the presence and absence of CBD was conducted in order to identify potential genes that mediated CBD’s neuroprotective effects. In the second, we assessed some of the same genes in male and female mice treated with CBD in the absence of an immune stimulus. Together these data showed that CBD modestly increased oxytocin (Oxt) and vasopressin (Avp) gene expression in the brains of mice, regardless of whether there was active inflammation, suggesting they might serve as biomarkers for CBD exposure, and perhaps, anti-inflammatory efficacy.
2024-07-03 | GSE262437 | GEO
Project description:Annetocin is structurally related to an OT (oxytocin)/VP (vasopressin) family peptide, which has been isolated from the earthworm Eisenia foetida and has been shown to induce OT-like egg-laying behaviour. We now report the identification of an endogenous AnR (annetocin receptor). The deduced AnR precursor displays high sequence similarity with OT/VP receptors. Genomic analysis of the AnR gene revealed that the intron-inserted position is conserved between the AnR gene and the mammalian OT/VP receptor genes. These results indicate that AnR and mammalian OT/VP receptors share a common ancestor gene. Administration of annetocin to the AnR expressed in Xenopus oocytes induced a calcium-dependent signal transduction. Reverse transcriptase-PCR analysis and in situ hybridization showed that the AnR gene is expressed specifically in the nephridia located in the clitellum region, although the nephridia are distributed throughout the worm body. This result suggests that annetocin induces egg-laying behaviour through its action on the nephridia. This is the first description concerning the functional correlation between an invertebrate OT/VP-related peptide and egg-laying behaviour.
| S-EPMC1133935 | biostudies-literature
Project description:Aggressive behavior in dogs poses public health and animal welfare concerns, however the biological mechanisms regulating dog aggression are not well understood. We investigated the relationships between endogenous plasma oxytocin (OT) and vasopressin (AVP)-neuropeptides that have been linked to affiliative and aggressive behavior in other mammalian species-and aggression in domestic dogs. We first validated enzyme-linked immunosorbent assays (ELISAs) for the measurement of free (unbound) and total (free + bound) OT and AVP in dog plasma. In Experiment 1 we evaluated behavioral and neuroendocrine differences between a population of pet dogs with a history of chronic aggression toward conspecifics and a matched control group. Dogs with a history of aggression exhibited more aggressive behavior during simulated encounters with conspecifics, and had lower free, but higher total plasma AVP than matched controls, but there were no group differences for OT. In Experiment 2 we compared OT and AVP concentrations between pet dogs and a population of assistance dogs that have been bred for affiliative and non-aggressive temperaments, and investigated neuroendocrine predictors of individual differences in social behavior within the assistance dog population. Compared to pet dogs, assistance dogs had higher free and total OT, but there were no differences in either measure for AVP. Within the assistance dog population, dogs who behaved more aggressively toward a threatening stranger had higher total AVP than dogs who did not. Collectively these data suggest that endogenous OT and AVP may play critical roles in shaping dog social behavior, including aspects of both affiliation and aggression.
| S-EPMC5624304 | biostudies-literature
Project description:BackgroundThe neuropeptides oxytocin and vasopressin have been repeatedly implicated in social decision making by enhancing social salience and, generally, cooperation. The iterated and sequential version of the prisoner's dilemma (PD) game is a social dilemma paradigm eliciting strategies of cooperation versus competition.AimsWe aimed to characterise the role of PD players' sex, game partner type (computer vs. human) and oxytocin or vasopressin inhalation on the player's strategy preference.MethodsParticipants (153 men; 151 women) were randomised to intranasal 24 IU oxytocin, 20 IU vasopressin or placebo, double-blind, and played the PD. We examined main and interactive effects of sex, drug and partner type on strategy preference.ResultsWe found a pervasive preference for a tit-for-tat strategy (i.e. general sensitivity to the partner's choices) over unconditional cooperation, particularly when against a human rather than a computer partner. Oxytocin doubled this sensitivity in women (i.e. the preference for tit-for-tat over unconditional cooperation strategies) when playing against computers, which suggests a tendency to anthropomorphise them, and doubled women's unconditional cooperation preference when playing against humans. Vasopressin doubled sensitivity to the partner's previous choices (i.e. for tit-for-tat over unconditional cooperation) across sexes and partner types.ConclusionsThese findings suggest that women may be more sensitive to oxytocin's social effects of anthropomorphism of non-humans and of unconditional cooperation with humans, which may be consistent with evolutionary pressures for maternal care, and that vasopressin, irrespective of sex and partner type, may be generally sensitising humans to others' behaviour.
| S-EPMC7583454 | biostudies-literature
Project description:Delta-Like 1 Homolog, Dlk1, is a paternally imprinted gene encoding a transmembrane protein involved in the differentiation of several cell types. After birth, Dlk1 expression decreases substantially in all tissues except endocrine glands. Dlk1 deletion in mice results in pre-natal and post-natal growth deficiency, mild obesity, facial abnormalities, and abnormal skeletal development, suggesting involvement of Dlk1 in perinatal survival, normal growth and homeostasis of fat deposition. A neuroendocrine function has also been suggested for DLK1 but never characterised. To evaluate the neuroendocrine function of DLK1, we first characterised Dlk1 expression in mouse hypothalamus and then studied post-natal variations of the hypothalamic expression. Western Blot analysis of adult mouse hypothalamus protein extracts showed that Dlk1 was expressed almost exclusively as a soluble protein produced by cleavage of the extracellular domain. Immunohistochemistry showed neuronal DLK1 expression in the suprachiasmatic (SCN), supraoptic (SON), paraventricular (PVN), arcuate (ARC), dorsomedial (DMN) and lateral hypothalamic (LH) nuclei. DLK1 was expressed in the dendrites and perikarya of arginine-vasopressin neurons in PVN, SCN and SON and in oxytocin neurons in PVN and SON. These findings suggest a role for DLK1 in the post-natal development of hypothalamic functions, most notably those regulated by the arginine-vasopressin and oxytocin systems.
| S-EPMC3338567 | biostudies-literature
Project description:The related neuropeptides oxytocin and vasopressin are involved in species-typical behavior, including social recognition behavior, maternal behavior, social bonding, communication, and aggression. A wealth of evidence from animal models demonstrates significant modulation of adult social behavior by both of these neuropeptides and their receptors. Over the last decade, there has been a flood of studies in humans also implicating a role for these neuropeptides in human social behavior. Despite popular assumptions that oxytocin is a molecule of social bonding in the infant brain, less mechanistic research emphasis has been placed on the potential role of these neuropeptides in the developmental emergence of the neural substrates of behavior. This review summarizes what is known and assumed about the developmental influence of these neuropeptides and outlines the important unanswered questions and testable hypotheses. There is tremendous translational need to understand the functions of these neuropeptides in mammalian experience-dependent development of the social brain. The activity of oxytocin and vasopressin during development should inform our understanding of individual, sex, and species differences in social behavior later in life.
| S-EPMC4262889 | biostudies-other
Project description:Domestication is of unquestionable importance to the technological revolution that has given rise to modern human societies. In this study, we analyzed the DNA and protein sequences of six genes of the oxytocin and arginine vasopressin systems (OXT-OXTR; AVP-AVPR1a, AVPR1b and AVPR2) in 40 placental mammals. These systems play an important role in the control of physiology and behavior. According to our analyses, neutrality does not explain the pattern of molecular evolution found in some of these genes. We observed specific sites under positive selection in AVPR1b (? = 1.429, p = 0.001) and AVPR2 (?= 1.49, p = 0.001), suggesting that they could be involved in behavior and physiological changes, including those related to the domestication process. Furthermore, AVPR1a, which plays a role in social behavior, is under relaxed selective constraint in domesticated species. These results provide new insights into the nature of the domestication process and its impact on the OXT-AVP system.
| S-EPMC5913714 | biostudies-literature
Project description:The neuropeptides oxytocin (OXT) and vasopressin (AVP) have been identified as modulators of emotional social behaviors and associated with neuropsychiatric disorders characterized by social dysfunction. Experimental and therapeutic use of OXT and AVP via the intranasal route is the subject of extensive clinical research. However, the large-scale functional substrates directly engaged by these peptides and their functional dynamics remain elusive. By using cerebral blood volume (CBV) weighted fMRI in the mouse, we show that intranasal administration of OXT rapidly elicits the transient activation of cortical regions and a sustained activation of hippocampal and forebrain areas characterized by high oxytocin receptor density. By contrast, intranasal administration of AVP produced a robust and sustained deactivation in cortico-parietal, thalamic and mesolimbic regions. Importantly, intravenous administration of OXT and AVP did not recapitulate the patterns of modulation produced by intranasal dosing, supporting a central origin of the observed functional changes. In keeping with this notion, hippocampal local field potential recordings revealed multi-band power increases upon intranasal OXT administration. We also show that the selective OXT-derivative TGOT reproduced the pattern of activation elicited by OXT and that the deletion of OXT receptors does not affect AVP-mediated deactivation. Collectively, our data document divergent modulation of brainwide neural systems by intranasal administration of OXT and AVP, an effect that involves key substrates of social and emotional behavior. The observed divergence calls for a deeper investigation of the systems-level mechanisms by which exogenous OXT and AVP modulate brain function and exert their putative therapeutic effects.
| S-EPMC5436116 | biostudies-literature
Project description:The neuropeptides oxytocin and vasopressin have increasingly been identified as modulators of human social behaviors and associated with neuropsychiatric disorders characterized by social dysfunction, such as autism. Identifying the human brain regions that are impacted by oxytocin and vasopressin in a social context is essential to fully characterize the role of oxytocin and vasopressin in complex human social cognition. Advances in human non-invasive neuroimaging techniques and genetics have enabled scientists to begin to elucidate the neurobiological basis of the influence of oxytocin and vasopressin on human social behaviors. Here we review the findings to-date from investigations of the acute and chronic effects of oxytocin and vasopressin on neural activity underlying social cognitive processes using "pharmacological fMRI" and "imaging genetics", respectively. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.
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