Vasopressin Expression Research Articles

Vasopressin and cardiovascular autonomic adjustment in chronic hypertensive pregnancy

Chronic hypertensive pregnancy (CHP) is a growing health issue with unknown etiology. Vasopressin (VP), a nonapeptide synthesized in paraventricular (PVN) and supraoptic nucleus (SON), is a well-known neuroendocrine and autonomic modulator of the cardiovascular system, related to hypertension development. We quantified gene expression of VP and its receptors, V1aR and V1bR, within the PVN and SON in CHP and normal pregnancy, and assessed levels of secreted plasma VP. Also, we evaluated autonomic cardiovascular adaptations to CHP using spectral indices of blood pressure (BPV) and heart rate (HRV) short-term variability, and spontaneous baroreflex sensitivity (BRS). Experiments were performed in female spontaneously hypertensive rats (SHRs) and in normotensive Wistar rats (WRs). Animals were equipped with a radiotelemetry probe for continuous hemodynamic recordings before and during pregnancy. BPV, HRV and BRS were assessed using spectral analysis and the sequence method, respectively. Plasma VP was determined by ELISA whilst VP, V1aR, and V1bR gene expression was analyzed by real-time-quantitative PCR (RT-qPCR). The results show that non-pregnant SHRs exhibit greater VP, V1aR, and V1bR gene expression in both PVN and SON respectively, compared to Wistar dams. Pregnancy decreased VP gene expression in the SON of SHRs but increased it in the PVN and SON of WRs. Pregnant SHRs exhibited a marked drop in plasma VP concentration associated with BP normalization. This triggered marked tachycardia, heart rate variability increase, and BRS increase in pregnant SHRs. It follows that regardless of BP normalization in late pregnancy, SHRs exhibit cardiovascular vulnerability and compensate by recruiting vagal mechanisms.Pregnant SHR dams have reduced expression of VP in SON associated with increased V1bR expression, lower plasma VP, normal BP during late pregnancy and marked signs of enhanced sympathetic cardiac stimulation (increased HR and LFHR variability) and recruitment of vagal mechanisms (enhancement of BRS and HFHR variability).

A vasopressin circuit that modulates mouse social investigation and anxiety-like behavior in a sex-specific manner

One of the largest sex differences in brain neurochemistry is the expression of the neuropeptide arginine vasopressin (AVP) within the vertebrate brain, with males having more AVP cells in the bed nucleus of the stria terminalis (BNST) than females. Despite the long-standing implication of AVP in social and anxiety-like behaviors, the circuitry underlying AVP's control of these behaviors is still not well defined. Using optogenetic approaches, we show that inhibiting AVP BNST cells reduces social investigation in males, but not in females, whereas stimulating these cells increases social investigation in both sexes, but more so in males. These cells may facilitate male social investigation through their projections to the lateral septum (LS), an area with the highest density of sexually differentiated AVP innervation in the brain, as optogenetic stimulation of BNST AVP → LS increased social investigation and anxiety-like behavior in males but not in females; the same stimulation also caused a biphasic response of LS cells ex vivo. Blocking the vasopressin 1a receptor (V1aR) in the LS eliminated all these responses. Together, these findings establish a sexually differentiated role for BNST AVP cells in the control of social investigation and anxiety-like behavior, likely mediated by their projections to the LS.

Effects of physical training on hypothalamic neuronal activation and expressions of vasopressin and oxytocin in SHR after running until fatigue.

To assess the influence of physical training on neuronal activation and hypothalamic expression of vasopressin and oxytocin in spontaneously hypertensive rats (SHR), untrained and trained normotensive rats and SHR were submitted to running until fatigue while internal body and tail temperatures were recorded. Hypothalamic c-Fos expression was evaluated in thermoregulatory centers such as the median preoptic nucleus (MnPO), medial preoptic nucleus (mPOA), paraventricular nucleus of the hypothalamus (PVN), and supraoptic nucleus (SON). The PVN and the SON were also investigated for vasopressin and oxytocin expressions. Although exercise training improved the workload performed by the animals, it was reduced in SHR and followed by increased internal body temperature due to tail vasodilation deficit. Physical training enhanced c-Fos expression in the MnPO, mPOA, and PVN of both strains, and these responses were attenuated in SHR. Vasopressin immunoreactivity in the PVN was also increased by physical training to a lesser extent in SHR. The already-reduced oxytocin expression in the PVN of SHR was increased in response to physical training. Within the SON, neuronal activation and the expressions of vasopressin and oxytocin were reduced by hypertension and unaffected by physical training. The data indicate that physical training counterbalances in part the negative effect of hypertension on hypothalamic neuronal activation elicited by exercise, as well as on the expression of vasopressin and oxytocin. These hypertension features seem to negatively influence the workload performed by SHR due to the hyperthermia derived from the inability of physical training to improve heat dissipation through skin vasodilation.

The transcription factor VAX1 in VIP neurons of the suprachiasmatic nucleus impacts circadian rhythm generation, depressive-like behavior, and the reproductive axis in a sex-specific manner in mice.

The suprachiasmatic nucleus (SCN) within the hypothalamus is a key brain structure required to relay light information to the body and synchronize cell and tissue level rhythms and hormone release. Specific subpopulations of SCN neurons, defined by their peptide expression, regulate defined SCN output. Here we focus on the vasoactive intestinal peptide (VIP) expressing neurons of the SCN. SCN VIP neurons are known to regulate circadian rhythms and reproductive function. To specifically study SCN VIP neurons, we generated a novel knock out mouse line by conditionally deleting the SCN enriched transcription factor, Ventral Anterior Homeobox 1 (Vax1), in VIP neurons (Vax1Vip; Vax1fl/fl:VipCre). We found that Vax1Vip females presented with lengthened estrous cycles, reduced circulating estrogen, and increased depressive-like behavior. Further, Vax1Vip males and females presented with a shortened circadian period in locomotor activity and ex vivo SCN circadian period. On a molecular level, the shortening of the SCN period was driven, at least partially, by a direct regulatory role of VAX1 on the circadian clock genes Bmal1 and Per2. Interestingly, Vax1Vip females presented with increased expression of arginine vasopressin (Avp) in the paraventricular nucleus, which resulted in increased circulating corticosterone. SCN VIP and AVP neurons regulate the reproductive gonadotropin-releasing hormone (GnRH) and kisspeptin neurons. To determine how the reproductive neuroendocrine network was impacted in Vax1Vip mice, we assessed GnRH sensitivity to a kisspeptin challenge in vivo. We found that GnRH neurons in Vax1Vip females, but not males, had an increased sensitivity to kisspeptin, leading to increased luteinizing hormone release. Interestingly, Vax1Vip males showed a small, but significant increase in total sperm and a modest delay in pubertal onset. Both male and female Vax1Vip mice were fertile and generated litters comparable in size and frequency to controls. Together, these data identify VAX1 in SCN VIP neurons as a neurological overlap between circadian timekeeping, female reproduction, and depressive-like symptoms in mice, and provide novel insight into the role of SCN VIP neurons.

A Brain Region-Dependent Alteration in the Expression of Vasopressin, Corticotropin-Releasing Factor, and Their Receptors Might Be in the Background of Kisspeptin-13-Induced Hypothalamic-Pituitary-Adrenal Axis Activation and Anxiety in Rats.

Previously, we reported that intracerebroventricularly administered kisspeptin-13 (KP-13) induces anxiety-like behavior and activates the hypothalamic-pituitary-adrenal (HPA) axis in rats. In the present study, we aimed to shed light on the mediation of KP-13's stress-evoking actions. The relative gene expressions of the corticotropin-releasing factor (Crf, Crfr1, and Crfr2) and arginine vasopressin (Avp, Avpr1a, and Avpr1b) systems were measured in the amygdala and hippocampus of male Wistar rats after icv KP-13 treatment. CRF and AVP protein content were also determined. A different set of animals received CRF or V1 receptor antagonist pretreatment before the KP-13 challenge, after which either an open-field test or plasma corticosterone levels measurement was performed. In the amygdala, KP-13 induced an upregulation of Avp and Avpr1b expression, and a downregulation of Crf. In the hippocampus, the mRNA level of Crf increased and the level of Avpr1a decreased. A significant rise in AVP protein content was also detected in the amygdala. KP-13 also evoked anxiety-like behavior in the open field test, which the V1 receptor blocker antagonized. Both CRF and V1 receptor blockers reduced the KP-13-evoked rise in the plasma corticosterone level. This suggests that KP-13 alters the AVP and CRF signaling and that might be responsible for its effect on the HPA axis and anxiety-like behavior.

Quantitative and molecular aspects of water intake in meat-type chickens

Even though water is the most essential nutrient for poultry production, adequate data on individual water intake in broiler chickens and its relationship with other traits of economic importance is scant. Water is provided to chickens in an unrestricted manner in spite of being a finite resource. Climate change continues to affect water sources and efficient bird use of water is long overdue. Understanding the biological basis of water intake is essential for sustainability of the poultry industry. Individual water and feed intake, and growth data was collected on 520 commercial broilers aged 14 to 42 days. We introduced the concepts of water conversion ratio (WCR) and residual water intake (RWI) as parameters that can be used to assess water intake efficiency. Water conversion ratio was defined as the amount of water consumed per unit of body weight gain, and RWI was defined as the difference between the actual water intake (WI) of a given bird and the expected WI by an average bird from the population with the same metabolic body weight, feed intake (FI) and body weight gain (BWG). The correlation between WI and FI was positive (r=0.77; P<0.0001), and the correlation between WI and BWG was positive (r=0.80; P<0.0001). Based on the distribution of RWI, the bottom 5 birds (LRWI) and the top 5 birds (HRWI) for RWI were selected for mRNA expression differences. The average broiler consumed about 7.8 L (± 1L) of water from 14 to 42 days of age. The mRNA expression of arginine vasopressin (AVP) antidiuretic hormone, calcium sensing receptor (CasR), sodium channel epithelial 1 subunit alpha (SCNN1A) and SCNN1D in the hypothalamus was upregulated in the LRWI group compared to the HRWI group. Similarly, kidney aquaporins (AQP) 2, 3, and 4 were upregulated in the LRWI group compared with the HRWI group. Given that water was provided ad libitum, the up-regulation of AVP and AQP gene mRNA expressions seem to indicate that the LRWI birds were more efficient in water reabsorption in the kidney compared to their HRWI counterparts. Increased water reabsorption will reduce the amount of water consumed to attain hydration. The water reabsorption potential was reflected in the excreta moisture levels as the LRWI birds had significantly lower excreta moisture than the HRWI birds. Excreta moisture level require further studies and could be considered as a potential proxy trait for water intake.

A Novel Early Life Stress Model Affects Brain Development and Behavior in Mice

Early life stress (ELS) in developing children has been linked to physical and psychological sequelae in adulthood. In the present study, we investigated the effects of ELS on brain and behavioral development by establishing a novel ELS model that combined the maternal separation paradigm and mesh platform condition. We found that the novel ELS model caused anxiety- and depression-like behaviors and induced social deficits and memory impairment in the offspring of mice. In particular, the novel ELS model induced more enhanced depression-like behavior and memory impairment than the maternal separation model, which is the established ELS model. Furthermore, the novel ELS caused upregulation of arginine vasopressin expression and downregulation of GABAergic interneuron markers, such as parvalbumin (PV), vasoactive intestinal peptide, and calbindin-D28k (CaBP-28k), in the brains of the mice. Finally, the offspring in the novel ELS model showed a decreased number of cortical PV-, CaBP-28k-positive cells and an increased number of cortical ionized calcium-binding adaptors-positive cells in their brains compared to mice in the established ELS model. Collectively, these results indicated that the novel ELS model induced more negative effects on brain and behavioral development than the established ELS model.

Adolescence Predatory Risk Alters Social Behaviors and Cognitive Ability and Central Oxytocin and Vasopressin Expression in Adult Brandt’s Voles

Introduction: Stress during adolescence causes long-term behavioral changes in adulthood. We previously found that adolescent exposure to predatory risk augments adolescent social contact and adult parental behavior in Brandt’s voles (Lasiopodomys brandtii). Methods: Here, we determined whether this experience alters sexual behavior, pair-bond formation, and recognition ability as well as basal HPA axis activity, central oxytocin (OT), and arginine-vasopressin (AVP) expression in adulthood. Results: In the social interaction test, repeated cat odor (CO) exposure enhanced the frequency of lordosis by female voles toward an unfamiliar opposite-sex conspecific. CO voles preferred to engage with their partners after 48-h cohabitation whereas the control groups did not, which may reflect stable pair bonds in the CO treatment group. Furthermore, adolescent exposure to CO inhibited novel object recognition and place recognition ability, while it influenced social recognition only among adult males. No effect of adolescent CO exposure was observed for basal HPA axis activity, showing a habituation effect. Finally, we found that CO exposure increased OT and decreased AVP expression in the hypothalamus, including the paraventricular nucleus and anterior hypothalamus. The levels of OT in the medial amygdala were lower, and AVP in the lateral septum was higher in CO voles compared with the control. Conclusion: These findings demonstrate that adolescent exposure to predator risk promotes adult reproductive behavior of Brandt’s voles. Deficits in recognition ability may necessitate alterations in reproductive strategies to enhance inclusive fitness. OT and AVP systems may play a modulatory role in the alteration of social behaviors elicited by adolescent predatory risk.

Expression of vasopressin and its receptors in migraine-related regions in CNS and the trigeminal system: influence of sex

BackgroundHypothalamus is a key region in migraine attacks. In addition, women are disproportionately affected by migraine. The calcitonin gene-related peptide (CGRP) system is an important key player in migraine pathophysiology. CGRP signaling could be a target of hormones that influence migraine. Our aim is to identify the expression of vasopressin and its receptors in the brain and in the trigeminovascular system with focus on the migraine-related regions and, furthermore, to examine the role of sex on the expression of neurohormones in the trigeminal ganglion.MethodsRat brain and trigeminal ganglia were carefully harvested, and protein and mRNA levels were analyzed by immunohistochemistry and real-time PCR, respectively.ResultsVasopressin and its receptors immunoreactivity were found in migraine-related areas within the brain and, in the trigeminal ganglion, predominantly in neuronal cytoplasm. There were no differences in the number of positive immunoreactivity cells expression of CGRP and vasopressin in the trigeminal ganglion between male and female rats. In contrast, the number of RAMP1 (CGRP receptor), oxytocin (molecular relative to vasopressin), oxytocin receptor and vasopressin receptors (V1aR and V1bR) immunoreactive cells were higher in female compared to male rats. Vasopressin and its receptors mRNA were expressed in both hypothalamus and trigeminal ganglion; however, the vasopressin mRNA level was significantly higher in the hypothalamus.ConclusionsA better understanding of potential hormonal influences on migraine mechanisms is needed to improve treatment of female migraineurs. It is intriguing that vasopressin is an output of hypothalamic neurons that influences areas associated with migraine. Therefore, vasopressin and the closely related oxytocin might be important hypothalamic components that contribute to migraine pathophysiology.

Early-life maternal deprivation affects the mother-offspring relationship in domestic pigs, as well as the neuroendocrine development and coping behavior of piglets.

Early-life adversity may have programming effects on the psychological and physiological development of offspring. Domestic pigs (Sus scrofa) are an excellent model species for studying these effects because of their many physiological similarities to humans. Piglets from 10 sows were subjected to daily 2-h maternal deprivation on postnatal days (PND) 2–15 alone (DA) or in a group of littermates (DG). Control piglets (C) from 10 sows stayed with their mothers. Mother-offspring interaction, milk oxytocin, and cortisol were analyzed. An open-field/novel-object (OF/NO) test was performed with piglets on PNDs 16 and 40. Plasma cortisol and immune parameters were determined on PND 5 and 16. Two piglets from each group and sow were sacrificed on PND 20 and stress-related gene expression in the limbic system and prefrontal cortex (PFC), as well as splenic lymphocyte proliferative abilities, were examined. The milk cortisol of sows increased during the first separation of mother and offspring on the second day of lactation, whereas milk oxytocin did not change. The increase in cortisol by the OF/NO test on PND 16 was greater in C piglets than in DA and DG ones. DA piglets showed less agitated behavior than DG and C piglets in the OF/NO test at PND 16, but appeared more fearful. On PND 40, DA piglets showed more arousal than DG and C piglets in the OF/NO test. Neither plasma IgA nor N/L ratios in blood nor mitogen-induced proliferation of spleen lymphocytes were affected by deprivation. We found a higher mRNA expression of CRHR1 in the hypothalamus and a higher expression of MR in the hippocampus in DA piglets than in DG ones. The expression of GR, MR, and CRHR1 genes in the PFC was reduced by maternal deprivation, however, the expression of arginine vasopressin and oxytocin receptors was not affected. Repeated maternal deprivation induces sustained effects on stress reactivity and behavior of domestic piglets. Some of these effects were buffered by the presence of littermates. In addition, we found sex-specific differences in behavior and gene expression.

Clomiphene citrate treatment during perinatal development alters adult partner preference, mating behaviour and androgen receptor and vasopressin in the male mandarin vole Microtus mandarinus.

During development, many aspects of behaviour, including partner preferences and sexual behaviour, are "organized" by neural aromatization of androgen and oestrogen. This study aimed to analyse these processes in the mandarin vole (Microtus mandarinus); this is a novel mammalian model exhibiting strong monogamous pair bonds. Male pups were treated daily with a sesame oil only (MC) or the oestrogen receptor blocker-clomiphene citrate sesame oil mixture (MT) from prenatal day 14 to postnatal day 10. Female pups were treated daily with sesame oil only (FC). Partner preferences, sexual behaviour, and the expression of androgen receptor (AR) and arginine vasopressin (AVP) were examined when animals were 3months old. The MT and FC groups exhibited male-directed partner preferences and feminized behaviour. AR-immunoreactive neurons (AR-IRs) in the medial preoptic area (mPOA), bed nucleus of stria terminalis (BNST), and medial amygdaloid nucleus (MeA) were reduced in MT males compared to MC males, and there was no significant difference in the number of AR-IRs between MT males and FC females. AVP-immunoreactive neurons (AVP-IRs) in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) were reduced in MT males compared to MC males, and there were no significant differences in the number of AVP-IRs between MT males and FC females. The results indicate a significant role of hormone signalling in the development of male mate preference in the novel monogamous mammal model.

The live biotherapeutic Blautia stercoris MRx0006 attenuates social deficits, repetitive behaviour, and anxiety-like behaviour in a mouse model relevant to autism

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by deficits in social behaviour, increased repetitive behaviour, anxiety and gastrointestinal symptoms. The aetiology of ASD is complex and involves an interplay of genetic and environmental factors. Emerging pre-clinical and clinical studies have documented a potential role for the gut microbiome in ASD, and consequently, the microbiota represents a potential target in the development of novel therapeutics for this neurodevelopmental disorder. In this study, we investigate the efficacy of the live biotherapeutic strain, Blautia stercoris MRx0006, in attenuating some of the behavioural deficits in the autism-relevant, genetic mouse model, BTBR T+ Itpr3tf/J (BTBR). We demonstrate that daily oral administration with MRx0006 attenuates social deficits while also decreasing repetitive and anxiety-like behaviour. MRx0006 administration increases the gene expression of oxytocin and its receptor in hypothalamic cells in vitro and increases the expression of hypothalamic arginine vasopressin and oxytocin mRNA in BTBR mice. Additionally at the microbiome level, we observed that MRx0006 administration decreases the abundance of Alistipes putredinis, and modulates the faecal microbial metabolite profile. This alteration in the metabolite profile possibly underlies the observed increase in expression of oxytocin, arginine vasopressin and its receptors, and the consequent improvements in behavioural outcomes. Taken together, these findings suggest that the live biotherapeutic MRx0006 may represent a viable and efficacious treatment option for the management of physiological and behavioural deficits associated with ASD.

Single Prolonged Stress Alters Vasopressin and Orexin System Expression in Sprague Dawley Rats

Posttraumatic stress disorder (PTSD) is a complex psychiatric disorder triggered by a terrifying event, causing severe anxiety and nightmares. Studies showed that patients with PTSD have increased risk of cardiovascular disease. However, the effect of PTSD on blood pressure remains unraveled. In this study, we test the hypothesis that PTSD alters expression of arginine vasopressin (AVP) and orexin system components and therefore increases blood pressure. Single prolonged stress (SPS) protocol including 2 hours of restraint, a 20‐min forced swimming and exposure to diethyl ether until loss of consciousness was used to create a PTSD model. Eight‐week‐old male Sprague Dawley (SD) rats were divided into two groups and treated with or without SPS, then all rats were single‐housed and remained undisturbed for 7 days. Their blood pressure (BP) and heart rates (HR) were recorded by radio telemetry transmitter system (Data Science International) prior to the treatment as baseline, and 1‐ day, and 7‐day post the treatment. The data showed that SPS significantly increased BP (ΔBP: 8.384 ± 1.187 mmHg, N=6 P&lt;0.05) and HR (ΔHR: 32.88 ± 9.149 beats/min, N=6 P&lt;0.05) compared to control rats (ΔBP: 2.346 ± 0.9324 mmHg, ΔHR: ‐1.503 ± 5.960 beats/min, N=8) on day 1 post treatment, but no significance difference was observed in BP and HR on day 7 compared to their own baseline and between SPS and control groups.To investigate whether AVP and orexin systems participate in PTSD development, we examined paraventricular nucleus (PVN) and adrenal gland AVP‐ and orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R) expression in both SD male and female rats with or without SPS at day 7. Our data showed that PVN AVP mRNA levels were increased by 2‐fold in the SPS group compared to control in male rats (P&lt;0.05) but this change was not observed in female rats. No changes were observed in PVN OX1R and OX2R mRNA levels between SPS and control rats in both males and females. Peripheral orexin receptors’ protein levels were altered but showed inconsistency in male and female rats: western blot data showed that adrenal gland OX1R protein levels were increased in the SPS group (control: 1.000 ± 0.07424 N=5 vs SPS: 1.531 ± 0.2016 N=5; P&lt;0.05) in male rats, while OX2R protein levels were decreased in female rats in female rats (control: 1.000 ± 0.01025 N=5 vs SPS: 0.8840 ± 0.04533 N=6; P&lt;0.05). Renal OX1R was also increased (control: 1.000 ± 0.02794 N=3 vs SPS: 1.374 ± 0.1385 N=3; P&lt;0.06) in female rats under SPS. ELISA assay showed that plasma orexin A levels were increased in female rats under SPS (control: 1.000 ± 0.1600 pg/mL N=3 vs SPS: 1.561 ± 0.1262 pg/mL; N=3 P&lt;0.05) but not in male rats.These results suggested that the central AVP system and peripheral orexin system may play a role in PTSD‐related high blood pressure development, and the peripheral orexin system may mediate stress response of female rats more than male rats. These molecular differences between SD male and female rats may also help to answer why females and males showed different responses to trauma. Further study will continue to find the PTSD‐sensitized hypertensive model and investigate specific functions of AVP and orexin system in PTSD.

Arcuate NPY is involved in salt-induced hypertension via modulation of paraventricular vasopressin and brain-derived neurotrophic factor.

Chronic high salt intake is one of the leading causes of hypertension. Salt activates the release of the key neurotransmitters in the hypothalamus such as vasopressin to increase blood pressure, and neuropepetide Y (NPY) has been implicated in the modulation of vasopressin levels. NPY in the hypothalamic arcuate nucleus (Arc) is best known for its control in appetite and energy homeostasis, but it is unclear whether it is also involved in the development of salt‐induced hypertension. Here, we demonstrate that wild‐type mice given 2% NaCl salt water for 8 weeks developed hypertension which was associated with marked downregulation of NPY expression in the hypothalamic Arc as demonstrated in NPY‐GFP reporter mice as well as by in situ hybridization analysis. Furthermore, salt intake activates neurons in the hypothalamic paraventricular nucleus (PVN) where mRNA expression of brain‐derived neurotrophic factor (BDNF) and vasopressin was found to be upregulated, leading to elevated serum vasopressin levels. This finding suggests an inverse correlation between the Arc NPY level and expression of vasopressin and BDNF in the PVN. Specific restoration of NPY by injecting AAV‐Cre recombinase into the Arc only of the NPY‐targeted mutant mice carrying a loxP‐flanked STOP cassette reversed effects of salt intake on vasopressin and BDNF expression, leading to a normalization of salt‐dependent blood pressure. In summary, our study uncovers an important Arc NPY‐originated neuronal circuitry that could sense and respond to peripheral electrolyte signals and thereby regulate hypertension via vasopressin and BDNF in the PVN.

Knockdown of sexually differentiated vasopressin expression in the bed nucleus of the stria terminalis reduces social and sexual behaviour in male, but not female, mice.

The neuropeptide arginine-vasopressin (AVP) has long been implicated in the regulation of social behaviour and communication, but the sources of AVP release relevant for behaviour have not been precisely determined. Ablations of the sexually dimorphic AVP cells within the bed nucleus of the stria terminalis (BNST), which are more numerous in males, affect social behaviour differently in males and females. However, it is unknown whether these behavioural effects are caused by a reduction of AVP or of other factors associated with these cells. To test the role of AVP specifically, we used an shRNA viral construct to knock down AVP gene expression within the BNST of wild-type male and female mice, using scrambled sequence virus as a control, and evaluated subsequent changes in social behaviours (social investigation, ultrasonic vocalization (USV), scent marking, copulation, and aggression), or anxiety-like behaviours (elevated plus maze). We observed that, in males, knockdown of AVP expression in the BNST strongly reduced investigation of novel males, aggressive signalling towards other males (tail rattling, USV), and copulatory behaviour, but did not alter attack initiation, other measures of social communication, or anxiety-like behaviours. In females, however, BNST AVP knockdown did not alter any of these behaviours. These results point to differential involvement of AVP derived from the BNST in social behaviour.

Environmental Enrichment Protects Against Sepsis-Associated Encephalopathy-Induced Learning and Memory Deficits by Enhancing the Synthesis and Release of Vasopressin in the Supraoptic Nucleus.

BackgroundAs a severe complication of sepsis, sepsis-associated encephalopathy (SAE) usually manifests as impaired learning and memory ability in survivors. Previous studies have reported that environmental enrichment (EE) can increase the learning and memory ability in different brain injury models. However, there has been no research on the possible positive effect of EE on SAE.AimThe present study aimed to test the effect of EE on SAE-induced impairment of learning and memory and its related mechanisms.MethodsA Morris water maze test (MWM) was used to evaluate the learning and memory ability of SAE rats that received EE housing or not. The expression of vasopressin (VP) was assessed using immunofluorescence microscopy and enzyme-linked immunosorbent assays (ELISAs). The synthesis of VP in the supraoptic nucleus (SON) was determined using quantitative real-time reverse transcription-PCR analysis. Moreover, inflammatory markers and brain-derived neurotrophic factor (BDNF) were detected using ELISA.ResultsThe results showed that SAE induced a decreased learning and memory ability, while EE reversed this impairment. EE also enhanced the synthesis and secretion of VP in the SON. Blocking the action of VP in the hippocampus interrupted the EE-induced amelioration of learning and memory impairment. Moreover, EE induced changes to the levels of BDNF and cytokines in the hippocampus and these effects were mediated by VP binding to the VP receptor 1a.ConclusionOur findings demonstrated that the enhanced synthesis and secretion of VP in the SON are a key determinant responsible for EE-induced alleviation of learning and memory deficits caused by SAE.

Support for the parental practice hypothesis: Subadult prairie voles exhibit similar behavioral and neural profiles when alloparenting kin and non-kin

Parental care is critical for offspring survival in altricial species. Although parents are the most common caregivers, other individuals (e.g., older siblings) can also provide alloparental care. Some have argued that animals engage in alloparental behavior to practice providing care for their eventual offspring, whereas others have argued that alloparental behavior enhances indirect fitness. Proximate measures have the potential to test ultimate functions of behavior. A focus on neural expression of oxytocin and vasopressin (two neuropeptides modulating alloparental care) or neural activation following exposure to related and unrelated individuals could reveal whether practice or investment in indirect fitness explains alloparental behavior. This study examined alloparental behaviors and neural responses in prairie voles (Microtus ochrogaster), a species that engages in alloparental behavior. Subadult (independent, yet sexually immature) male prairie voles were exposed to one of four stimuli: same-age sibling, neonatal sibling, unrelated neonate, or inanimate neonate-sized object. We assessed alloparental behaviors and quantified cFos protein expression in oxytocin and vasopressin neuronal populations of the paraventricular nucleus of the hypothalamus and the supraoptic nucleus of the hypothalamus in response to stimulus exposure. We detected no differences in cFos and nonapeptide co-localization among stimulus groups. Subjects performed similar amounts of alloparental care toward related and unrelated neonates, but not other subadults or inanimate objects. Notably, caregiving did not differ based on kin-status. The lack of difference in alloparenting toward related and non-related neonates suggests that alloparental care in prairie voles primarily serves to provide subadults with parental practice.

Vasopressin and oxytocin expression in hypothalamic supraoptic nucleus and plasma electrolytes changes in water-deprived male Meriones libycus

ABSTRACT In mammals, plasmatic osmolality needs to be stable, and it is highly related to the hydric state of the animals which depends on the activity of the hypothalamic neurohypophysial system and more particularly by vasopressin secretion. Meriones, a desert rodent, can survive even without drinking for more than one month. The mechanism(s) by which they survive under these conditions remains poorly understood. In this study, we examine the water’s deprivation consequences on the: (1) anatomy, morphology, and physiology of the hypothalamic supraoptic nucleus, (2) body mass and plasma electrolytes changes in male desert rodents ‘Meriones libycus’ subjected to water deprivation for 30 days. The effect of water deprivation was evaluated on the structural and cellular organization of the supraoptic nucleus by morphological observations and immunohistochemical approaches, allowing the labeling of AVP but also oxytocin. Our finding demonstrated that upon water deprivation (1) the body weight decreased and reached a plateau after a month of water restriction. (2) The plasmatic osmolality began to decrease and return to values similar to control animals at day 30. (3) The SON, both in hydrated and water-deprived animals, is highly developed.(4) The AVP labeling in the SON increased upon dehydration at variance with OT. These changes observed in body mass and plasma osmolality reveal an important adaptive process of male Meriones in response to prolonged water deprivation. Overall, this animal represents an interesting model for the study of water body homeostasis and the mechanisms underlying the survival of desert rodents to xeric environments.

Epigenetic Modulation of Vasopressin Expression in Health and Disease.

Vasopressin is a ubiquitous molecule playing an important role in a wide range of physiological processes thereby implicated in the pathomechanism of many disorders. Its effect is well characterized through V2 receptors, which regulates the water resorption in kidney, while its vasoconstrictory effect through V1a receptor also received a lot of attention in the maintenance of blood pressure during shock. However, the most striking is its central effect both through the V1b receptors in stress-axis regulation as well as through V1a receptors regulating many aspects of our behavior (e.g., social behavior, learning and memory). Vasopressin has been implicated in the development of depression, due to its connection with chronic stress, as well as schizophrenia because of its involvement in social interactions and memory processes. Epigenetic changes may also play a role in the development of these disorders. The possible mechanism includes DNA methylation, histone modification and/or micro RNAs, and these possible regulations will be in the focus of our present review.

Hyperosmolarity-induced vasopressin expression and intrinsic excitability of supraoptic neurons of adult offspring are changed by early maternal separation

Adverse early life experiences can produce long-lasting changes in neurocircuits. The aim of this study was to investigate the programming effects of early maternal separation on the adult offspring vasopressin system. We hypothesized that subjecting adult rats to 4.5 h of daily maternal separation between postnatal days 1 – 21 will have altered hyperosmolarity-induced Avp expression and the response of supraoptic (SON) neurons to electrical and osmotic stimulation. We measured Avp mRNA and hn-RNA in the SON and in the paraventricular nucleus (PVN) by quantitative PCR, and assessed the intrinsic excitability of magnocellular SON neurons as well as their osmotic responses by the patch-clamp technique. In maternally-separated rats we found that basal and osmolarity-induced Avp mRNA gene expression was upregulated in the SON, whereas osmolarity-induced Avp hn-RNA gene expression was abolished. Similarly, in the PVN of maternally-separated rats the osmolarity-induced Avp mRNA gene expression was blunted. The supraoptic neurons of separated rats also had greater excitability than those of non-separated rats. Our results indicate that early maternal separation has long-term consequences on basal and hyperosmolarity-induced Avp hypothalamic expression as well as on the intrinsic excitability of magnocellular supraoptic neurons.