Consequences of chronic psychosocial stress in male wistar rats

In humans, chronic stress is regarded as a major risk factor for the development of a variety of affective and somatic disorders, among them anxiety, depression, post traumatic stress disorder, inflammatory bowel disorders, chronic fatigue syndrome, chronic pelvic pain and fibromyalgia. In order to determine the exact underlying mechanisms and also to find pharmacological treatment, a large number of models have been used to induce chronic stress in rodents. However, conventional rodent models of chronic stress including restraint, forced swim and inescapable footshock for example; are unnaturalistic, of time-limited exposure and do not consider the etiology of human stress-associated disorders, where the main source of stress stimuli is of social origin. Consequently, a greater amount of attention has been focused upon developing animal models that utilize more naturalistic experimental paradigms to model stress that is ethologically relevant to the model organism. Accordingly, a clinically relevant animal model of chronic psychosocial stress (CPS); chronic subordinate colony housing (CSC) has recently been established and extensively characterized in our group. It consists of housing 4 experimental adult male mice together with a slightly larger and more dominant conspecific over 19 consecutive days, exchanging the dominant male weekly in order to prevent habituation. This consequently results in a reduced body weight gain, thymus atrophy and increased adrenal weight, long-lasting anxiety-like behaviour, and spontaneous colitis. Of particular importance to this thesis is the unchanged morning basal plasma corticosterone, but a reduced adrenal response to corticotrophin (ACTH) in vitro. With respect to the growing use of genetic mouse models in general, and the need to study in vivo responsiveness of the HPA axis especially with regards to the CSC model, one of the objectives of this thesis was to devise a technique by which blood samples can be repeatedly drawn from conscious mice under stress-free conditions. Therefore, a simplified jugular vein catheterization technique was established and validated. This thesis showed that repeated blood sampling is possible in mice 24 h after surgery, and that corticosterone concentrations in repeated 100-μl venous blood samples were similar to trunk blood, both collected under basal conditions and at identical time points (5, 15 and 60 min) after stressor exposure. Further, anxiety-related behavior, as assessed on the elevated plus-maze 3 to 4 days after surgery did not differ between catheterized and non-catheterized mice. In parallel, as the main objective of this thesis, the CSC model was extended to male Wistar rats in order to i), investigate if the reported behavioral, physiological, immunological and neuroendocrine changes accompanying CSC in mice are species specific and ii), characterize in substantial detail, in vivo neuroendocrine changes following CSC which till moment have not been possible in mice, e.g plasma ACTH. Consistent with the results in mice, 19 days of CSC exposure in rats resulted in a decreased body weight gain and absolute thymus mass, mild colonic barrier defects and intestinal immune activation. Moreover, no changes in depressive-like behaviour or social preference were observed. Most importantly, CSC rats showed an increased plasma corticosterone response to an acute heterotypic stressor, despite displaying similar basal levels and similar basal and stressor-induced plasma corticotrophin (ACTH) levels in samples repeatedly collected via a chronically implanted jugular vein catheter. In contrast to CSC mice, anxiety-related behaviour and absolute adrenal weights remained unchanged in CSC rats. In this regard, risk factors that could influence the susceptibility to CSC were further investigated. There is a plethora of literature addressing the involvement of adverse early life events and genetic predisposition as risk factors in the vulnerability to chronic stress in adulthood. Therefore, this thesis made use the high (HAB) and low (LAB) anxiety-related behaviour animal models of anxiety, as well as prenatally stressed male Wistar offspring. Specifically, HAB and LAB rats also show robust differences in depressive-like behaviour, neurobiochemical responses and neurogenetic constitution. It was therefore revealed that after 19 days of CSC, prenatally stressed rats gained less body weight and had a higher histological damage score. No changes in adrenal weight, basal plasma corticosterone levels, as well as anxiety-related behaviour were observed. The present study could not reveal any difference in HAB and LAB rats in their response to CSC in adulthood, but both lines were independently affected by CSC. Anxiety-related behaviour tested in the light-dark box after CSC was not altered, thus confirming the results in non-selected rats. CSC induced a decrease in body weight gain and thymus mass, but no changes in adrenal mass, basal plasma corticosterone and colonic morphology in both HAB and LAB rats. In a nutshell, this thesis demonstrates that chronic jugular vein catheterization and stress-free repeated blood sampling is possible in conscious mice using our relatively simple catheter and sampling technique. It also establishes the CSC paradigm as an adequate model of CPS in male rats. Consistent to mice data, our data from repeated blood sampling supports the initial hypothesis that adrenal hyper-responsiveness to ACTH during acute heterotypic stressors represents a general adaptation, which enables a chronically-stressed animal to adequately respond to novel challenges. We further reveal that early life stress increases the vulnerability to chronic psychosocial stressors during adulthood, with respect to inflammatory disorders like colitis and that genetic predisposition, in terms of genetically determined differences in innate anxiety-related behaviour do not shape susceptibility to chronic psychosocial stressors during adulthood

Syncretism and inculturation in the Nso’ context of Cameroon

This article gives a brief history and meaning of the terms syncretism and inculturation. The article highlights the fact that over the centuries Christianity has wrestled with syncretism. Following Lamin Sanneh (1989) the authors discuss three styles Christianity has employed in engaging cultures with the Gospel. The three styles are: quarantine, syncretist, and reform. The article draws examples from the history of missions to illustrate how this went on; showing what happened when Christianity engaged the Jewish community and the Greco-Roman world. The article argues that inculturation is not “everything goes”. Using the Nso’1 context of Cameroon, the authors critique inculturation which leads to syncretism and suggest holistic “translatability” and holistic “critical contextualisation” as a way out.http://ojs.reformedjournals.co.za/index.php/stjam2017Science of Religion and Missiolog

Magnetic resonance imaging, computed tomography, and 68Ga-DOTATOC positron emission tomography for imaging skull base meningiomas with infracranial extension treated with stereotactic radiotherapy - a case series

<p>Abstract</p> <p>Introduction</p> <p>Magnetic resonance imaging (MRI) and computed tomography (CT) with ⁶⁸Ga-DOTATOC positron emission tomography (⁶⁸Ga-DOTATOC-PET) were compared retrospectively for their ability to delineate infracranial extension of skull base (SB) meningiomas treated with fractionated stereotactic radiotherapy.</p> <p>Methods</p> <p>Fifty patients with 56 meningiomas of the SB underwent MRI, CT, and ⁶⁸Ga-DOTATOC PET/CT prior to fractionated stereotactic radiotherapy. The study group consisted of 16 patients who had infracranial meningioma extension, visible on MRI ± CT (MRI/CT) <it>or </it>PET, and were evaluated further. The respective findings were reviewed independently, analyzed with respect to correlations, and compared with each other.</p> <p>Results</p> <p>Within the study group, SB transgression was associated with bony changes visible by CT in 14 patients (81%). Tumorous changes of the foramen ovale and rotundum were evident in 13 and 8 cases, respectively, which were accompanied by skeletal muscular invasion in 8 lesions. We analysed six designated anatomical sites of the SB in each of the 16 patients. Of the 96 sites, 42 had infiltration that was delineable by MRI/CT and PET in 35 cases and by PET only in 7 cases. The mean infracranial volume that was delineable in PET was 10.1 ± 10.6 cm³, which was somewhat larger than the volume detectable in MRI/CT (8.4 ± 7.9 cm³).</p> <p>Conclusions</p> <p>⁶⁸Ga-DOTATOC-PET allows detection and assessment of the extent of infracranial meningioma invasion. This method seems to be useful for planning fractionated stereotactic radiation when used in addition to conventional imaging modalities that are often inconclusive in the SB region.</p

The cooperative sex: Sexual interactions among female bonobos are linked to increases in oxytocin, proximity and coalitions

In some species habitual same-sex sexual behavior co-occurs with high levels of intra-sexual alliance formation, suggesting that these behaviors may be linked. We tested for such a link by comparing behavioral and physiological outcomes of sex with unrelated same- and opposite-sex partners in female bonobos (Pan paniscus). We analyzed behavioral outcomes following 971 sexual events involving n = 19 female and n = 8 male adult and sub-adult members of a wild, habituated bonobo community. We additionally collected n = 143 urine samples before and after sexual interactions to non-invasively measure oxytocin (OT), which modulates female sexual behavior and facilitates cooperation in other species. The majority of sexual events (65%) consisted of female same-sex genito-genital rubbing (or GG-rubbing). Female dyads engaged in significantly more sexual interactions than did inter-sexual dyads, and females were more likely to remain within close proximity to their partners following GG-rubbing. Females also exhibited greater increases in urinary OT following GG-rubbing compared with copulations, indicating a physiological basis for increased motivation to cooperate among females. The frequency of coalitionary support among non-kin was positively predicted by the frequency of sexual interactions for female as well opposite-sex dyads, although coalitionary support tended to be more frequent among females. The emergence of habitual same-sex sexual behavior may have been an important step in the evolution of cooperation outside of kinship and pair-bonds in one of our closest phylogenetic relatives

Cytokine-mediated blood brain barrier disruption as a conduit for cancer/chemotherapy-associated neurotoxicity and cognitive dysfunction

Neurotoxicity is a common side effect of chemotherapy treatment, with unclear molecular mechanisms. Clinical studies suggest that the most frequent neurotoxic adverse events affect memory and learning, attention, concentration, processing speeds and executive function. Emerging preclinical research points toward direct cellular toxicity and induction of neuroinflammation as key drivers of neurotoxicity and subsequent cognitive impairment. Emerging data now show detectable levels of some chemotherapeutic agents within the CNS, indicating potential disruption of blood brain barrier integrity or transport mechanisms. Blood brain barrier disruption is a key aspect of many neurocognitive disorders, particularly those characterized by a proinflammatory state. Importantly, many proinflammatory mediators able to modulate the blood brain barrier are generated by tissues and organs that are targets for chemotherapy-associated toxicities. This review therefore aims to explore the hypothesis that peripherally derived inflammatory cytokines disrupt blood brain barrier permeability, thereby increasing direct access of chemotherapeutic agents into the CNS to facilitate neuroinflammation and central neurotoxicity.Hannah R. Wardill, Kimberley A. Mander, Ysabella Z.A. Van Sebille, Rachel J. Gibson, Richard M. Logan, Joanne M. Bowen, and Stephen T. Soni

Yes, I Am Ready Now: Differential Effects of Paced versus Unpaced Mating on Anxiety and Central Oxytocin Release in Female Rats

Sexual activity and partner intimacy results in several positive consequences in the context of stress-coping, both in males and females, such as reduced state anxiety in male rats after successful mating. However, in female rats, mating is a rewarding experience only when the estrous female is able to control sexual interactions, i.e., under paced-mating conditions. Here, we demonstrate that sex-steroid priming required for female mating is anxiolytic; subsequent sexual activity under paced mating conditions did not disrupt this anxiolytic priming effect, whereas mating under unpaced conditions increased anxiety-related behavior. In primed females, the release of the neuropeptide oxytocin (OT) within the hypothalamic paraventricular nucleus was found to be elevated and to further increase during paced, but not unpaced mating. Central administration of an OT receptor antagonist partly prevented priming/mating-induced anxiolysis indicating the involvement of brain OT in the anxiolysis triggered by priming and/or sexual activity

PET directed neurosurgery and radiation therapy of brain tumors

Die CT und MRT stellen die wichtigsten Verfahren für die Routinediagnostik, Therapieplanung und Nachsorge von Hirntumoren dar. Einschränkungen dieser bildgebenden Verfahren sind eine unzureichende Unterscheidung postoperativer oder postaktinischer Veränderungen vom Rest- oder Rezidivtumor und eine mangelhafte Differenzierbarkeit des vitalen Tumors von perifokalem Ödem. Die Positronen-Emissions-Tomographie (PET) kommt immer häufiger bei der prä- und posttherapeutischen Diagnostik sowie bei der Therapieplanung von Hirntumoren zum Einsatz. Die vorgelegten Studien haben den Einsatz der PET für die Planung der Chirurgie und Strahlentherapie von Hirntumoren evaluiert. In einer simulativen Studie wurde der Einfluss der 68Ga-DOTATOC PET im Vergleich zur CT/MRT auf die Planung der stereotaktischen Strahlentherapie von Meningeomen untersucht. Dazu wurden 42 Patienten mit CT, MRT und PET untersucht. Das Tumorvolumen wurde einmal unter Verwendung von CT/MRT und einmal nur anhand der PET definiert und miteinander verglichen. Die PET erlaubt eine bessere Abgrenzung des vitalen Tumorgewebes von posttherapeutischen Veränderungen und liefert therapierelevante Zusatzinformationen über die Tumorausdehnung. In einer prospektiven Studie wurde bei 13 Patienten die Anwendung der 18F-FET PET für die chirurgische Resektion von malignen Gliomen untersucht. Eine Verbesserung der Tumorsektion und das Überleben für einige Gliompatienten durch die 5-Aminolävulinsäure (5-ALA) fluoreszenzgestützte Mikrochirurgie wurde schon berichtet. Unsere Arbeit untersuchte, ob das Tumorvolumen, welches präoperativ mithilfe der 18F-FET PET definiert werden kann, mit dem intraoperativ anhand von 5-ALA Fluoreszenz darstellbaren Tumorvolumen bei malignen Gliomen übereinstimmt. Die PET konnte mit einer hohen Sensivität und Spezifizität die 5-ALA-induzierte Fluoreszenz in malignen Gliomen voraussagen und stellt eine alternative Methode für die Resektionsplanung von Gliomen dar. Bei Gliompatienten hängen therapierelevante Entscheidungen und Prognose vom Tumorgrad ab. Wegen möglicher Heterogenität kann eine fehlgeleitete Biopsie zu einer fehlerhaften Tumorgrad-Bestimmung führen. In einer weiteren prospektiven Studie wurde bei 15 Patienten mit Gliomen ohne Gd-Anreicherung in MRT die Anwendung von 18F-FET PET und 18F-FDG PET für die Selektion der Biopsiestelle verglichen. 18F-FET PET lieferte mehr Information als 18F-FDG PET und ist die Methode der Wahl zur Bestimmung der Biopsiestelle. Somit wird durch unsere Studien die Bedeutung der PET als bildgebendes Verfahren für die Planung der Neurochirurgie und Strahlentherapie bei Hirntumoren hervorgehoben.CT and MRI are currently the most important tools for the diagnostic, therapy planning follow-up of patients with primary brain tumors. An important limitation of these diagnostic tools is amongst others an inadequate differentiation of therapy induced changes and perifocal edema from viable tumor tissue. Positron emission computer tomography (PET) is gaining grounds for the above mentioned purposes. The presented studies have examined the role of PET for planning of neurosurgery and radiation therapy of primary brain tumors