Biomedical subjects

Elisabeth Frank

Publications and source records attributed to Elisabeth Frank.

7 recordsLinked to original sources

PubMed2006

Candidate genes of anxiety-related behavior in HAB/LAB rats and mice: focus on vasopressin and glyoxalase-I.

Two animal models of trait anxiety, HAB/LAB rats and mice, are described, representing inborn extremes in anxiety-related behavior. The comprehensive phenotypical characterization included basal behavioral features, stress-coping strategies and neuroendocrine responses upon stressor exposure with HAB animals being hyper-anxious, preferring passive coping, emitting more stressor-induced ultrasonic vocalization calls and showing typical peculiarities of the hypothalamic-pituitary-adrenocortical axis and line-specific patterns of Fos expression in the brain indicative of differential neuronal activation. In most cases, unselected Wistar rats and CD1 mice, respectively, displayed intermediate behaviors. In both HAB/LAB rats and mice, the behavioral phenotype has been found to be significantly correlated with the expression of the neuropeptide arginine vasopressin (AVP) at the level of the hypothalamic paraventricular nucleus (PVN). Additional receptor antagonist approaches in HABs confirmed that intra-PVN release of AVP is likely to contribute to hyper-anxiety and depression-like behavior. As shown exemplarily in HAB rats and LAB mice, single nucleotide polymorphisms (SNPs) in regulatory structures of the AVP gene underlie AVP-mediated phenotypic phenomena; in HAB rats, a SNP in the promoter of the AVP gene leads to reduced binding of the transcriptional repressor CBF-A, thus causing AVP overexpression and overrelease. Conversely, in LAB mice, a SNP in the AVP gene seems to cause an amino acid exchange in the signal peptide, presumably leading to a deficit in bioavailable AVP likely to underlie the total hypo-anxiety of LAB mice in combination with signs of central diabetes insipidus. Another feature of LAB mice is overexpression of glyoxalase-I. The functional characterization of this enzyme will determine its involvement in anxiety-related behavior beyond that of a reliable biomarker. The further identification of quantitative trait loci, candidate genes (and their products) and SNPs will not only help to explain inter-individual variation in emotional behavior, but will also reveal novel targets for anxiolytic and antidepressive interventions.

Animals↗

PubMed2006

Airjet and FG-7142-induced Fos expression differs in rats selectively bred for high and low anxiety-related behavior.

We reported recently that two rat lines bred for either high (HAB) or low (LAB) anxiety-related behavior display differential Fos expression in restricted parts of the fear/anxiety circuitry when exposed to mild anxiety evoked in exploratory anxiety tests. Since different forms of anxiety are thought to activate different parts of the anxiety circuitry, we investigated now whether (1) an aversive stimulus which elicits escape behavior (airjet) and (2) the anxiogenic/panicogenic drug FG-7142 would reveal further differences in Fos expression as a marker of neuronal activation between HAB and LAB rats. Both airjet exposure and FG-7142 induced Fos expression in both lines in various anxiety-related brain areas. HAB rats, which displayed exaggerated escape responses during airjet exposure, exhibited increased Fos expression in brain areas including the hypothalamus, periaqueductal gray and locus coeruleus, as well as blunted Fos activation in the cingulate cortex in response to airjet and/or FG-7142. The results corroborate previous findings showing that trait anxiety affects neuronal excitability in hypothalamic and medial prefrontal areas. Furthermore, by using airjet as well as FG-7142, we now reveal that enhanced trait anxiety is also associated with neuronal hyperexcitability in the locus coeruleus and the periaqueductal gray, suggesting that investigation of an array of different anxiogenic stimuli is important for the detection of altered neuronal processing in trait anxiety.

Air↗

PubMed2006

Genetic predisposition to anxiety-related behavior determines coping style, neuroendocrine responses, and neuronal activation during social defeat.

Genetic background may influence an individual's susceptibility to, and subsequent coping strategy for, an acute stressor. When exposed to social defeat (SD), rats bred for high (HAB) or low (LAB) trait anxiety, which also differ in depression-like behavior, showed highly divergent passive and active coping behaviors, respectively. HABs spent more time freezing and emitted more ultrasound vocalization calls during SD than LABs, which spent more time rearing and grooming. Although the behavioral data confirmed the prediction that heightened trait anxiety would make rats more prone to experience stress, adrenocorticotropin and corticosterone were secreted to a higher extent in LABs than in HABs. In the latter, Fos expression upon SD was enhanced in the amygdala and hypothalamic areas compared with LABs, whereas it was diminished in prefrontal and brainstem areas.

Adaptation, Psychological↗

PubMed2004

Impaired repression at a vasopressin promoter polymorphism underlies overexpression of vasopressin in a rat model of trait anxiety.

Two inbred rat lines have been developed that show either high (HAB) or low (LAB) anxiety-related behavior. The behavioral phenotype correlates with arginine vasopressin (AVP) expression at the level of the hypothalamic paraventricular nucleus (PVN), but not supraoptic nucleus, with HAB animals overexpressing the neuropeptide in both magnocellular and parvocellular subdivisions of the PVN. We detected a number of single nucleotide polymorphisms (SNPs) in the AVP locus that differ between the HAB and LAB animals, two of which were embedded in cis-regulatory elements. The HAB-specific allele of the AVP gene promoter occurs in 1.5% of outbred Wistar rats and is more transcriptionally active in vivo, as revealed by allele-specific transcription studies in cross-mated HAB/LAB F1 animals. Interestingly, one specific SNP [A(-1276)G] conferred reduced binding of the transcriptional repressor CArG binding factor A (CBF-A) in the HAB allele, the consequent differential regulation of the AVP promoter resulting in an overexpression of AVP in vitro and in vivo. Furthermore, CBF-A is highly coexpressed in AVP-containing neurons of the PVN supporting an important role for regulation of AVP gene expression in vivo. Taken together, our results demonstrate a role for an AVP gene polymorphism and CBF-A in elevated AVP expression in the PVN of HAB rats likely to contribute to their behavioral and neuroendocrine phenotype.

Alleles↗

PubMed2004

Alterations in central neuropeptide expression, release, and receptor binding in rats bred for high anxiety: critical role of vasopressin.

To model aspects of trait anxiety/depression, Wistar rats were bred for extremes in either hyper (HAB)- or hypo(LAB)-anxiety as measured on the elevated plus-maze and in a variety of additional behavioral tests. Similar to psychiatric patients, HAB rats prefer passive stress-coping strategies, indicative of depression-like behavior, show hyper-reactivity of the hypothalamo-pituitary-adrenal axis, and a pathological response to the dexamethasone/corticotropin-releasing hormone (CRH) challenge test. Here we tested central mRNA expression, release patterns, and receptor binding of neuropeptides critically involved in the regulation of both anxiety-related behavior and the HPA axis. Thus, CRH, arginine-8-vasopressin (AVP), and oxytocin (OXT) were studied in brains of HAB and LAB males both under basal conditions and after exposure to a mild emotional stressor. In HAB rats, CRH mRNA was decreased in the bed nucleus of the stria terminalis only. While no significant difference in CRH1-receptor binding was found in any brain area, CRH2-receptor binding was elevated in the hypothalamic paraventricular nucleus (PVN), the ventromedial hypothalamus, and the central amygdala of HABs compared to LABs. AVP, but not OXT, mRNA expression as well as release of the neuropeptide, were higher in the PVN of HABs, whereas AVP V1a-receptor binding failed to show significant differences in any brain region studied. Remarkably, intra-PVN treatment of HABs with the AVP V1-receptor antagonist d (CH(2))(5) Tyr (Me) AVP resulted in a decrease in anxiety/depression-related behavior. The elevated expression and release of AVP within the PVN of HAB rats together with the behavioral effects of the AVP V1-receptor antagonist suggest a critical involvement of this neuropeptide in neuroendocrine and behavioral phenomena associated with trait anxiety/depression.

Analysis of Variance↗

PubMed2003

Viral vector-mediated gene transfer of the vole V1a vasopressin receptor in the rat septum: improved social discrimination and active social behaviour.

This study explores the effects of enhancing vasopressin V1a receptor expression in the septum using viral vector-mediated gene transfer on social discrimination and social interactions. Bilateral infusion of an adeno-associated viral vector containing the prairie vole V1a receptor gene (V1aR-AAV) regulated by a neuron-specific enolase promoter resulted in a stable increase in V1a receptor binding density in the rat septum without affecting oxytocin receptor density. Control animals were infused with a vector expressing the lacZ gene. In a social discrimination paradigm, only V1aR-AAV-treated animals succeeded in discriminating a previously encountered from a novel juvenile after an interexposure interval (IEI) of more than 2 h, demonstrating the functional incorporation of the vole V1a receptor in the rat septal circuits underlying short-term memory processes. Microdialysis administration of synthetic vasopressin during the first juvenile exposure, used to mimic intraseptal release patterns of the neuropeptide, produced similar prolongations in recognition (up to an IEI of 24 h) in both V1aR-AAV and control animals. Septal microdialysis administration of a selective V1a, but not oxytocin, receptor antagonist in both groups prevented discrimination even after an IEI of as short as 0.5 h, confirming the specificity of the vole V1a receptor involvement in social discrimination abilities. In addition, active social interactions were found to be increased among V1aR-AAV rats compared to controls. Viral vector-mediated gene transfer provides a valuable tool for studies on the role of localized gene expression on behavioural parameters.

Animals↗

PubMed2002

Approach versus avoidance: different types of commitment in intimate relationships.

The major objective of the present study was to examine whether approach versus avoidance commitment to one's intimate relationship was differentially predictive of relationship quality parameters in the long run. In the 1st testing period, 134 participants (67 romantic couples) answered questions about approach- versus avoidance-related measures. Commitment and relationship quality parameters such as satisfaction and emotions depending on the partner's presence were assessed in all 3 testing periods. The proposed distinction between an approach and an avoidance type of commitment was validated through correlations with other approach- versus avoidance-related measures. Longitudinal analyses revealed that approach commitment predicted relationship quality parameters positively, whereas avoidance commitment predicted them negatively. The results are discussed in terms of the benefit of an approach-avoidance-based conceptualization of commitment.

Avoidance Learning↗