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Identification of a Role for the Ventral Hippocampus in Neuropeptide S-Elicited Anxiolysis  [PDF]
Julien Dine, Irina A. Ionescu, Jens Stepan, Yi-Chun Yen, Florian Holsboer, Rainer Landgraf, Matthias Eder, Ulrike Schmidt
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0060219
Abstract: Neuropeptide S (NPS) increasingly emerges as a potential novel treatment option for anxiety diseases like panic and posttraumatic stress disorder. However, the neural underpinnings of its anxiolytic action are still not clearly understood. Recently, we reported that neurons of the ventral hippocampus (VH) take up intranasally administered fluorophore-conjugated NPS and, moreover, that application of NPS to mouse brain slices affects neurotransmission and plasticity at hippocampal CA3-CA1 synapses. Although these previous findings define the VH as a novel NPS target structure, they leave open whether this brain region is directly involved in NPS-mediated anxiolysis and how NPS impacts on neuronal activity propagation in the VH. Here, we fill this knowledge gap by demonstrating, first, that microinjections of NPS into the ventral CA1 region are sufficient to reduce anxiety-like behavior of C57BL/6N mice and, second, that NPS, via the NPS receptor, rapidly weakens evoked neuronal activity flow from the dentate gyrus to area CA1 in vitro. Additionally, we show that intranasally applied NPS alters neurotransmission and plasticity at CA3-CA1 synapses in the same way as NPS administered to hippocampal slices. Thus, our study provides, for the first time, strong experimental evidence for a direct involvement of the VH in NPS-induced anxiolysis and furthermore presents a novel mechanism of NPS action.
Neuropeptide-inducible upregulation of proteasome activity precedes nuclear factor kappa B activation in androgen-independent prostate cancer cells
Anna Patrikidou, Panagiotis J Vlachostergios, Ioannis A Voutsadakis, Eleana Hatzidaki, Rosalia-Maria Valeri, Chariklia Destouni, Effie Apostolou, Christos N Papandreou
Cancer Cell International , 2012, DOI: 10.1186/1475-2867-12-31
Abstract: We have now investigated for evidence of a direct mechanistic connection between these pathways with the use of immunocytochemistry (ICC), western blot analysis, electrophoretic mobility shift assay (EMSA) and proteasome activity assessment.Neuropeptide (NP) stimulation induced nuclear translocation of NFκB in a dose-dependent manner in AI cells, also evident as reduced total inhibitor κB (IκB) levels and increased DNA binding in EMSA. These effects were preceded by increased 20?S proteasome activity at lower doses and at earlier times and were at least partially reversed under conditions of NP deprivation induced by specific NP receptor inhibitors, as well as NFκB, IκB kinase (IKK) and proteasome inhibitors. AD cells showed no appreciable nuclear translocation upon NP stimulation, with less intense DNA binding signal on EMSA.Our results support evidence for a direct mechanistic connection between the NPs and NFκB/proteasome signaling pathways, with a distinct NP-induced profile in the more aggressive AI cancer state.The NFκB transcription factor controls many processes that influence carcinogenesis and cancer progression. Over-expression of NFκB and its transcribed genes are involved in tumor growth, angiogenesis, metastasis, and appear to be correlated with resistance to chemotherapy, advanced tumor stage, PSA recurrence and pre-surgical PSA levels in PC [1-3]. Indeed, there is recent evidence that IL-6 exposure (an NFκB target gene product) induces neuroendocrine differentiation of PC tumour sub-clones, conveying anti-apoptotic phenotype and resistance to chemotherapy [4,5]. Furthermore, activation of NFκB was proved to be sufficient to maintain androgen-independent growth of prostate and PC by up-regulating androgen receptor action [6].The ubiquitin-proteasome system (UPS) is an indispensable cellular regulatory machine with proteolytic and non-proteolytic functions affecting many cancer-related processes including cell cycle regulation, oxidation damage control
Effect of social instigation and aggressive behavior on hormone levels of lactating dams and adult male Wistar rats
Veiga, Caroline Perinazzo da;Aranda, Bruno Carlo Cerpa;Stein, Dirson;Franci, Celso Rodrigues;Miczek, Klaus A.;Lucion, Aldo Bolten;Almeida, Rosa Maria Martins de;
Psychology & Neuroscience , 2011, DOI: 10.3922/j.psns.2011.1.012
Abstract: among rodents, maternal aggression in the postpartum period represents a species-typical adaptation, but when aggressive behavior increases beyond this adaptive level, it can represent a model of excessive aggression. this study assessed the neuroendocrine response of lactating rats and socially instigated male rats. the aim of the present study was to assess neuroendocrine responses and the behavioral pattern of lactating rats and males that were subjected to an emotional stressor using the social instigation protocol. we measured plasma corticosterone levels as the key hormonal parameter of the hypothalamic-pituitary-adrenal (hpa) axis and oxytocin, prolactin, and progesterone, which are released in response to several types of stressors. our results showed that lactating rats that were subjected to only social instigation or aggressive confrontation in the presence of their pups had lower plasma corticosterone levels, and this response was similar to oxytocin, prolactin, and progesterone levels. by contrast, male rats showed increased corticosterone levels after being subjected only to social instigation. male rats also engaged in aggressive behavior compared with the control group. in conclusion, this study demonstrated that lactating rats subjected to social instigation exhibited an attenuation of the hpa axis response, which is considered to be crucial to the dam's welfare so that it can care for its offspring. thus, we can infer that lactation is a relevant factor in neuroendocrine responses to stress because of the increased levels of corticosterone in males.
Effect of social instigation and aggressive behavior on hormone levels of lactating dams and adult male Wistar rats
Caroline Perinazzo da Veiga,Bruno Carlo Cerpa Aranda,Dirson Stein,Celso Rodrigues Franci
Psychology & Neuroscience , 2011,
Abstract: Among rodents, maternal aggression in the postpartum period represents a species-typical adaptation, but when aggressive behavior increases beyond this adaptive level, it can represent a model of excessive aggression. This study assessed the neuroendocrine response of lactating rats and socially instigated male rats. The aim of the present study was to assess neuroendocrine responses and the behavioral pattern of lactating rats and males that were subjected to an emotional stressor using the social instigation protocol. We measured plasma corticosterone levels as the key hormonal parameter of the hypothalamic-pituitary-adrenal (HPA) axis and oxytocin, prolactin, and progesterone, which are released in response to several types of stressors. Our results showed that lactating rats that were subjected to only social instigation or aggressive confrontation in the presence of their pups had lower plasma corticosterone levels, and this response was similar to oxytocin, prolactin, and progesterone levels. By contrast, male rats showed increased corticosterone levels after being subjected only to social instigation. Male rats also engaged in aggressive behavior compared with the control group. In conclusion, this study demonstrated that lactating rats subjected to social instigation exhibited an attenuation of the HPA axis response, which is considered to be crucial to the dam’s welfare so that it can care for its offspring. Thus, we can infer that lactation is a relevant factor in neuroendocrine responses to stress because of the increased levels of corticosterone in males.
Foster Dams Rear Fighters: Strain-Specific Effects of Within-Strain Fostering on Aggressive Behavior in Male Mice  [PDF]
Kimberly H. Cox, Nina L. T. So, Emilie F. Rissman
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0075037
Abstract: It is well known that genes and environment interact to produce behavioral phenotypes. One environmental factor with long-term effects on gene transcription and behavior is maternal care. A classic paradigm for examining maternal care and genetic interactions is to foster pups of one genetic strain to dams of a different strain ("between-strain fostering"). In addition, fostering to a dam of the same strain ("within-strain fostering") is used to reduce indirect effects, via behavioral changes in the dams, of gestation treatments on offspring. Using within-and between-strain fostering we examined the contributions of genetics/prenatal environment, maternal care, and the effects of fostering per se, on adult aggressive behavior in two inbred mouse strains, C57BL/6J (B6) and DBA/2J (DBA). We hypothesized that males reared by dams of the more aggressive DBA strain would attack intruders faster than those reared by B6 dams. Surprisingly, we found that both methods of fostering enhanced aggressive behavior, but only in B6 mice. Since all the B6 offspring are genetically identical, we asked if maternal behavior of B6 dams was affected by the relatedness of their pups. In fact, B6 dams caring for foster B6 pups displayed significantly reduced maternal behaviors. Finally, we measured vasopressin and corticotrophin releasing hormone mRNA in the amygdalae of adult B6 males reared by foster or biological dams. Both genes correlated with aggressive behavior in within-strain fostered B6 mice, but not in mice reared by their biological dams. In sum, we have demonstrated in inbred laboratory mice, that dams behave differently when rearing their own newborn pups versus pups from another dam of the same strain. These differences in maternal care affect aggression in the male offspring and transcription of Avp and Crh in the brain. It is likely that rearing by foster dams has additional effects and implications for other species.
A rare benign genitourinary tumor in a Japanese male: urinary retention owing to aggressive angiomyxoma of the prostate  [cached]
Yugo Sawada,Fumio Ito,Hayakazu Nakazawa,Nobuhiko Tsushima
Rare Tumors , 2010, DOI: 10.4081/rt.2010.e15
Abstract: Close examination of a 67-year-old Japanese man, who complained of persistent nocturia, revealed that a semitransparent polypoid tumor had developed from the bladder neck to the prostatic urethra obstructing the internal urethral meatus, which resulted in excessive urinary retention and post-renal dysfunction. The tumor was resected by a transurethral procedure and a pathological examination of specimens revealed aggressive angiomyxoma (AAM) of the prostate. AAM usually develops in the intrapelvic and perineal organs of females. So far as we know, this is the second case of primary prostatic AAM reported in the English literature, and is the first case where the patient encountered urethral obstruction.
Neuropeptide W  [PDF]
Fumiko Takenoya,Haruaki Kageyama,Satoshi Hirako,Eiji Ota,Nobuhiro Wada,Tomoo Ryushi,Seiji Shioda
Frontiers in Endocrinology , 2012, DOI: 10.3389/fendo.2012.00171
Abstract: Neuropeptide W (NPW), which was first isolated from the porcine hypothalamus, exists in two forms, consisting of 23 (NPW23) or 30 (NPW30) amino acids. These neuropeptides bind to one of two NPW receptors, either NPBWR1 (otherwise known as GPR7) or NPBWR2 (GPR8), which belong to the G protein-coupled receptor family. GPR7 is expressed in the brain and peripheral organs of both humans and rodents, whereas GPR8 is not found in rodents. GPR7 mRNA in rodents is widely expressed in several hypothalamic regions, including the paraventricular, supraoptic, ventromedial, dorsomedial, suprachiasmatic, and arcuate nuclei. These observations suggest that GPR7 plays a crucial role in the modulation of neuroendocrine function. The intracerebroventricular infusion of NPW has been shown to suppress food intake and body weight and to increase both heat production and body temperature, suggesting that NPW functions as an endogenous catabolic signaling molecule. Here we summarize our current understanding of the distribution and function of NPW in the brain.
Depressive and Aggressive Responses to Frustration: Development of a Questionnaire and Its Validation in a Sample of Male Alcoholics  [PDF]
M. Y. Baars,M. J. Müller,B. Gallhofer,P. Netter
Depression Research and Treatment , 2011, DOI: 10.1155/2011/352048
Abstract: Since clinical and biochemical observations point to much overlap between depression and aggression, both characterised by intolerance to frustration, a questionnaire was developed to test if different patterns of depressive and aggressive reactions elicited by exposure to negative events and deprivation from expected positive ones in human and nonhuman conditions, respectively, would result in specific response patterns in depressive and aggressive persons. The questionnaire was tested for internal consistency in a pilot healthy sample and for correlations of responses with the personality factors of Aggression and Depression in 60 abstinent male alcoholics. Aggressive and depressive responses were highly correlated across all stimulus conditions, and not specifically but rather equally associated with the personality factors of Aggression and Depression, confirming the close association between these dimensions. 1. Introduction Since the present paper deals with aggression and depression in the context of a psychopathological disorder, the following consideration has to be addressed as a premise. It has already been claimed by Kretschmer [1] and Eysenck [2] that symptoms of psychiatric diseases may be observed on a milder level in nonclinical populations which suggests a continuum between disease and normal behavior. Psychologists used some of these symptoms as items to construct scales by factor analysis for specific pathology related personality traits like depression or aggression. Such scales nowadays usually form subscales of broader personality inventories like the NEO-PI-R used for assessment of the five factor model of personality. When applied to clinical samples, personality scales like those of the NEO-PI-R have been shown to be predictive of specific personality disorders [3, 4]. Scales of neuroticism, depression, and anxiety yield higher scores in depressed patients [5, 6], and scales measuring reactive or spontaneous aggression yield higher means in patients with impulse control disturbances, antisocial personality disorders [7] or alcohol dependence [8] than in nonclinical groups. Therefore, scores of depression and aggression on personality tests are conceived as models for respective psychopathological symptoms. Depression and aggression are considered to belong to different classes of diagnoses according to psychiatric classification systems (DSM-IV and ICD-10) and to different factors in personality inventories (e.g., NEO-PI-R). Yet, there is biochemical and clinical evidence for a relationship between the two constructs. Since the
An experimental test of the role of structural blue and melanin-based chestnut coloration in aggressive contests in male eastern bluebirds  [PDF]
Geoffrey E. Hill
Frontiers in Ecology and Evolution , 2014, DOI: 10.3389/fevo.2014.00024
Abstract: Male eastern bluebirds (Sialia sialis) have feathers with either structurally based blue coloration or melanin-based chestnut coloration, and they hold territories during the breeding season that they defend vigorously. We tested whether the melanin pigmentation or structural coloration of feathers serve as signals during intrasexual aggressive encounters by placing color-modified stuffed bluebirds in male territories. We recorded the time to attack and the intensity of attacks on each model, and we then compared the response to color-enhanced vs. color-reduced models. Male bluebirds attacked models with brighter and more chromatic blue coloration significantly more often than they attacked models with darker and less chromatic blue coloration. In contrast, the darkness of the chestnut breast coloration did not have a significant effect on the rate at which models were attacked. We conclude that territorial male bluebirds perceive intruding males with brighter blue coloration as a greater threat than males with drabber blue coloration, presumably because blue coloration is a signal of fighting ability. In contrast, the chestnut coloration of breast feathers appears to be a signal of gender and sexual maturity and not a graded signal of social status.
Divergent Evolution of Male Aggressive Behaviour: Another Reproductive Isolation Barrier in Extremophile Poeciliid Fishes?  [PDF]
David Bierbach,Moritz Klein,Vanessa Sassmannshausen,Ingo Schlupp,Rüdiger Riesch,Jakob Parzefall,Martin Plath
International Journal of Evolutionary Biology , 2012, DOI: 10.1155/2012/148745
Abstract: Reproductive isolation among locally adapted populations may arise when immigrants from foreign habitats are selected against via natural or (inter-)sexual selection (female mate choice). We asked whether also intrasexual selection through male-male competition could promote reproductive isolation among populations of poeciliid fishes that are locally adapted to extreme environmental conditions [i.e., darkness in caves and/or toxic hydrogen sulphide (H2S)]. We found strongly reduced aggressiveness in extremophile Poecilia mexicana, and darkness was the best predictor for the evolutionary reduction of aggressiveness, especially when combined with presence of H2S. We demonstrate that reduced aggression directly translates into migrant males being inferior when paired with males from nonsulphidic surface habitats. By contrast, the phylogenetically old sulphur-endemic P. sulphuraria from another sulphide spring area showed no overall reduced aggressiveness, possibly indicating evolved mechanisms to better cope with H2S. 1. Introduction 1.1. Ecological Speciation Divergent natural selection has the potential to drive adaptive trait divergence along environmental gradients [1], but can also lead to the evolution of reproductive isolating barriers [2, 3]. During ecological speciation, reproductive isolation results from ecologically based divergent selection, and prezygotic isolation may arise as a byproduct of local adaptation if immigrants from ecologically divergent habitats are selected against [3]. This can be owing to natural selection, if immigrants show reduced viability [4–6], or sexual selection, if poorly adapted individuals have a disadvantage in mate competition [5, 7, 8]. Furthermore, ecological speciation may also be driven by selection against hybrids with intermediate phenotypes [9], behavioural isolation based on a “magic trait” [10–14], and sensory drive [15]. Our present paper briefly collates our current knowledge regarding trait divergence and especially mechanisms of reproductive isolation among different locally adapted populations of livebearing fishes (Poeciliidae), currently undergoing ecological speciation processes in response to “extreme” conditions (see below). Using both lab-reared as well as wild-caught fish we then demonstrate that divergent evolution of male competitive abilities (aggressive behaviour) in extremophile fishes may play yet another role in maintaining reproductive isolation among different locally adapted populations: adaptation to extreme habitat conditions appears to have selected for reduced aggressiveness,
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