CRF1-R Activation of the Dynorphin/Kappa Opioid System in the Mouse Basolateral Amygdala Mediates Anxiety-Like Behavior

Stress is a complex human experience and having both rewarding and aversive motivational properties. The adverse effects of stress are well documented, yet many of underlying mechanisms remain unclear and controversial. Here we report that the anxiogenic properties of stress are encoded by the endogenous opioid peptide dynorphin acting in the basolateral amygdala. Using pharmacological and genetic approaches, we found that the anxiogenic-like effects of Corticotropin Releasing Factor (CRF) were triggered by CRF1-R activation of the dynorphin/kappa opioid receptor (KOR) system. Central CRF administration significantly reduced the percent open-arm time in the elevated plus maze (EPM). The reduction in open-arm time was blocked by pretreatment with the KOR antagonist norbinaltorphimine (norBNI), and was not evident in mice lacking the endogenous KOR ligand dynorphin. The CRF1-R agonist stressin 1 also significantly reduced open-arm time in the EPM, and this decrease was blocked by norBNI. In contrast, the selective CRF2-R agonist urocortin III did not affect open arm time, and mice lacking CRF2-R still showed an increase in anxiety-like behavior in response to CRF injection. However, CRF2-R knockout animals did not develop CRF conditioned place aversion, suggesting that CRF1-R activation may mediate anxiety and CRF2-R may encode aversion. Using a phosphoselective antibody (KORp) to identify sites of dynorphin action, we found that CRF increased KORp-immunoreactivity in the basolateral amygdala (BLA) of wildtype, but not in mice pretreated with the selective CRF1-R antagonist, antalarmin. Consistent with the concept that acute stress or CRF injection-induced anxiety was mediated by dynorphin release in the BLA, local injection of norBNI blocked the stress or CRF-induced increase in anxiety-like behavior; whereas norBNI injection in a nearby thalamic nucleus did not. The intersection of stress-induced CRF and the dynorphin/KOR system in the BLA was surprising, and these results suggest that CRF and dynorphin/KOR systems may coordinate stress-induced anxiety behaviors and aversive behaviors via different mechanisms

A prebiotic, Celmanax™, decreases Escherichia coli O157:H7 colonization of bovine cells and feed-associated cytotoxicity in vitro

<p>Abstract</p> <p>Background</p> <p><it>Escherichia coli </it>O157:H7 is the most common serovar of enterohemorrhagic <it>E. coli </it>associated with serious human disease outbreaks. Cattle are the main reservoir with <it>E. coli </it>O157:H7 inducing hemorrhagic enteritis in persistent shedding beef cattle, however little is known about how this pathogen affects cattle health. Jejunal Hemorrhage Syndrome (JHS) has unclear etiology but the pathology is similar to that described for <it>E. coli </it>O157:H7 challenged beef cattle suggestive that <it>E. coli </it>O157:H7 could be involved. There are no effective treatments for JHS however new approaches to managing pathogen issues in livestock using prebiotics and probiotics are gaining support. The first objective of the current study was to characterize pathogen colonization in hemorrhaged jejunum of dairy cattle during natural JHS outbreaks. The second objective was to confirm the association of mycotoxigenic fungi in feeds with the development of JHS and also to identify the presence of potential mycotoxins. The third objective was to determine the impact of a prebiotic, Celmanax™, or probiotic, Dairyman's Choice™ paste, on the cytotoxicity associated with feed extracts <it>in vitro</it>. The fourth objective was to determine the impact of a prebiotic or a probiotic on <it>E. coli </it>O157:H7 colonization of mucosal explants and a bovine colonic cell line <it>in vitro</it>. The final objective was to determine if prebiotic and probiotic feed additives could modify the symptoms that preceded JHS losses and the development of new JHS cases.</p> <p>Findings</p> <p>Dairy cattle developed JHS after consuming feed containing several types of mycotoxigenic fungi including <it>Fusarium culmorum</it>, <it>F. poae</it>, <it>F. verticillioides</it>, <it>F. sporotrichioides</it>, <it>Aspergillus</it><it>flavus</it>, <it>Penicillium roqueforti, P. crustosum, P. paneum </it>and <it>P. citrinum</it>. Mixtures of Shiga toxin - producing <it>Escherichia coli </it>(STEC) colonized the mucosa in the hemorrhaged tissues of the cattle and no other pathogen was identified. The STECs expressed Stx1 and Stx2, but more significantly, Stxs were also present in the blood clot blocking the jejunum. Mycotoxin analysis of the corn crop confirmed the presence of fumonisin, NIV, ZEAR, DON, 15-ADON, 3-ADON, NEO, DAS, HT-2 and T-2. Feed extracts were toxic to enterocytes and 0.1% Celmanax™ removed the cytotoxicity <it>in vitro</it>. There was no effect of Dairyman's Choice™ paste on feed-extract activity <it>in vitro</it>. Fumonisin, T-2, ZEAR and DON were toxic to bovine cells and 0.1% Celmanax™ removed the cytotoxicity <it>in vitro</it>. Celmanax™ also directly decreased <it>E. coli </it>O157:H7 colonization of mucosal explants and a colonic cell line in a dose-dependent manner. There was no effect of Dairyman's Choice™ paste on <it>E. coli </it>O157:H7 colonization <it>in vitro</it>. The inclusion of the prebiotic and probiotic in the feed was associated with a decline in disease.</p> <p>Conclusion</p> <p>The current study confirmed an association between mycotoxigenic fungi in the feed and the development of JHS in cattle. This association was further expanded to include mycotoxins in the feed and mixtures of STECs colonizing the severely hemorrhaged tissues. Future studies should examine the extent of involvement of the different STEC in the infection process. The prebiotic, Celmanax™, acted as an anti-adhesive for STEC colonization and a mycotoxin binder <it>in vitro</it>. Future studies should determine the extent of involvement of the prebiotic in altering disease.</p

A waitlist-controlled trial of group cognitive behavioural therapy for depression and anxiety in Parkinson’s disease

Background: The aim of this study was to evaluate the efficacy of a group Cognitive Behavioural Therapy (CBT) treatment for depression and anxiety in Parkinson’s disease (PD). Methods: A waitlist-controlled trial design was used. Eighteen adults with PD and a comorbid DSM-IV-TR diagnosis of depression and/or anxiety were randomised to either Intervention (8-week group CBT treatment) or Waitlist (8-week clinical monitoring preceding treatment). The Depression, Anxiety, Stress Scale-21 (DASS-21) was the primary outcome. Assessments were completed at Time 1 (pretreatment), Time 2 (posttreatment/post-waitlist) and 1-month and 6-month follow-ups. Results: At Time 2, participants who received CBT reported greater reductions in depression (Mchange = -2.45) than Waitlist participants (Mchange = .29) and this effect was large, d = 1.12, p = .011. Large secondary effects on anxiety were also observed for CBT participants, d = .89, p = .025. All treatment gains were maintained and continued to improve during the follow-up period. At 6-month follow-up, significant and large effects were observed for both depression (d = 2.07) and anxiety (d = 2.26). Conclusions: Group CBT appears to be an efficacious treatment approach for depression and anxiety in PD however further controlled trials with larger numbers of participants are required

Viewing Loved Faces Inhibits Defense Reactions: A Health-Promotion Mechanism?

We have known for decades that social support is associated with positive health outcomes. And yet, the neurophysiological mechanisms underlying this association remain poorly understood. The link between social support and positive health outcomes is likely to depend on the neurophysiological regulatory mechanisms underlying reward and defensive reactions. The present study examines the hypothesis that emotional social support (love) provides safety cues that activate the appetitive reward system and simultaneously inhibit defense reactions. Using the startle probe paradigm, 54 undergraduate students (24 men) viewed black and white photographs of loved (romantic partner, father, mother, and best friend), neutral (unknown), and unpleasant (mutilated) faces. Eye–blink startle, zygomatic major activity, heart rate, and skin conductance responses to the faces, together with subjective ratings of valence, arousal, and dominance, were obtained. Viewing loved faces induced a marked inhibition of the eye-blink startle response accompanied by a pattern of zygomatic, heart rate, skin conductance, and subjective changes indicative of an intense positive emotional response. Effects were similar for men and women, but the startle inhibition and the zygomatic response were larger in female participants. A comparison between the faces of the romantic partner and the parent who shares the partner’s gender further suggests that this effect is not attributable to familiarity or arousal. We conclude that this inhibitory capacity may contribute to the health benefits associated with social support.This research was funded by grant P07-SEJ-02964 from Junta de Andalucía (Spain)

The effects of CRF antagonists, antalarmin, CP154,526, LWH234, and R121919, in the forced swim test and on swim-induced increases in adrenocorticotropin in rats

Exposure to extreme stress has been suggested to produce long-term, detrimental alterations in the hypothalamic–pituitary–adrenal (HPA) axis leading to the development of mental disorders such as depression. Therefore, compounds that block the effects of stress hormones were investigated as potential therapeutics for depression.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46365/1/213_2005_Article_2164.pd

Alectorioid morphologies in Paleogene lichens : New evidence and re-evaluation of the fossil Alectoria succini Mägdefrau

One of the most important issues in molecular dating studies concerns the incorporation of reliable fossil taxa into the phylogenies reconstructed from DNA sequence variation in extant taxa. Lichens are symbiotic associations between fungi and algae and/or cyanobacteria. Several lichen fossils have been used as minimum age constraints in recent studies concerning the diversification of the Ascomycota. Recent evolutionary studies of Lecanoromycetes, an almost exclusively lichen-forming class in the Ascomycota, have utilized the Eocene amber inclusion Alectoria succinic as a minimum age constraint. However, a re-investigation of the type material revealed that this inclusion in fact represents poorly preserved plant remains, most probably of a root. Consequently, this fossil cannot be used as evidence of the presence of the genus Alectoria (Parmeliaceae, Lecanorales) or any other lichens in the Paleogene. However, newly discovered inclusions from Paleogene Baltic and Bitterfeld amber verify that alectorioid morphologies in lichens were in existence by the Paleogene. The new fossils represent either a lineage within the alectorioid group or belong to the genus Oropogon.Peer reviewe

Plasma oxytocin concentration during pregnancy is associated with development of postpartum depression

Postpartum depression (PPD) affects up to 19% of all women after parturition. The non-apeptide oxytocin (OXT) is involved in adjustment to pregnancy, maternal behavior, and bonding. Our aim was to examine the possible association between plasma OXT during pregnancy and the development of PPD symptoms. A total of 74 healthy, pregnant women were included in this prospective study. During the third trimester of pregnancy and within 2 weeks after parturition, PPD symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS). Blood samples for plasma OXT assessment were collected in the third trimester. Following the literature, participants with postpartum EPDS scores of 10 or more were regarded as being at risk for PPD development (rPPD group). In a logistic regression analysis, plasma OXT was included as a potential predictor for being at risk for PPD. Results were controlled for prepartal EPDS score, sociodemographic and birth-outcome variables. Plasma OXT concentration in mid-pregnancy significantly predicted PPD symptoms at 2 weeks postpartum. Compared with the no-risk-for-PPD group, the rPPD group was characterized by lower plasma OXT concentrations. To our knowledge, this is the first study to show an association between prepartal plasma OXT concentration and postpartal symptoms of PPD in humans. Assuming a causal relationship, enhancing OXT release during pregnancy could serve as a potential target in prepartum PPD prevention, and help to minimize adverse effects of PPD on the mother-child relationship