Spatial Learning Deficits in Mice with a Targeted Glucocorticoid Receptor Gene Disruption

Previous studies in rats using the Morris water maze suggested that the processing of spatial information is modulated by corticosteroid hormones through mineralocorticoid and glucocorticoid receptors in the hippocampus. Mineralocorticoid receptors appear to be involved in the modulation of explorative behaviour, while additional activation of glucocorticoid receptors facilitates the storage of information. In the present study we used the water maze task to examine spatial learning and memory in mice homozygous and heterozygous for a targeted disruption of the glucocorticoid receptor gene. Compared with wild-type controls, homozygous and heterozygous mice were impaired in the processing of spatial but not visual information. Homozygous mutants performed variably during training, without specific platform-directed search strategies. The spatial learning disability was partly compensated for by increased motor activity. The deficits were indicative of a dysfunction of glucocorticoid receptors as well as of mineralocorticoid receptors. Although the heterozygous mice performed similarly to wild-type mice with respect to latency to find the platform, their strategy was more similar to that of the homozygous mice. Glucocorticoid receptor-related long-term spatial memory was impaired. The increased behavioural reactivity of the heterozygous mice in the open field points to a more prominent mineralocorticoid receptor-mediated function. The findings indicate that (i) the glucocorticoid receptor is of critical importance for the control of spatial behavioural functions, and (ii) mineralocorticoid receptor-mediated effects on this behaviour require interaction with functional glucocorticoid receptors. Until the development of site-specific, inducible glucocorticoid receptor mutants, glucocorticoid receptor-knockout mice present the only animal model for the study of corticosteroid-mediated effects in the complete absence of a functional receptor.     

Subjective work noise: A major risk factor in myocardial infarction

Summary The relationship between subjective work noise exposure and the risk of myocardial infarction (MI) was assessed in a population based casecontrol study. 395 MI patients (31–65 years) were compared to 2148 controls from a random population sample with the same age/sex distribution. The relative risk (RR) for MI—adjusted for control variables (smoking, age, social status, etc.)—was found to increase significantly and steadily with noise category. Subjective work noise exposure was the second greatest risk factor for MI after smoking. Possible bias due to overreporting of subjective noise exposure is discussed. Interdisciplinary studies on the relationship between cardiovascular diseases and workrelated stressors including subjective and objective noise assessment are needed to quantify the risk of MI due to work noise.

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Zusammenfassung In einer bevölkerungsbezogenen Fall-Kontroll-Studie wurde der Zusammenhang zwischen der subjektiven Arbeitslärmbelastung und dem Herzinfarktrisiko untersucht. 395 Herzinfarktpatienten im Alter von 31 bis 65 Jahren wurden mit 2148 Kontrollpersonen aus einer Zufallsstichprobe mit gleicher Alters- und Geschlechtsverteilung verglichen. Das relative Risiko für Herzinfarkt—adjustiert bezüglich mehrerer Einflussvariablen wie Rauchen, Alter, Sozialstatus usw.—stieg signifikant und monoton mit der Arbeitslärmbelastung an. Die subjektive Arbeitslärmbelastung erwies sich als der zweitwichtigste Risikofaktor für Herzinfarkt nach dem Rauchen. Mögliche Fehler wie z.B. Überbewertung der subjektiven Lärmbelastung werden diskutiert. Interdisziplinäre Studien zum Zusammenhang zwischen kardiovaskulären Erkrankungen und arbeitsplatzbezogenen Stressoren mit Erfassung der subjektiven und der objektiven Lärmbelastung sind notwendig, um das Herzinfarktrisiko durch Arbeitslärm zu quantifizieren.

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Résumé Le rapport entre la perception subjective de bruit gênant et le risque d'infarctus du myocarde (IM) fait l'objet d'une étude comparative portant sur 395 malades (IM) âgés de 31 à 65 ans et 2148 cas témoins sortis d'un sondage aléatoire parmi la population générale tout en assurant la même distribution d'âge et de sexe. II s'avère que—après la rectification exigée par les variables telles que consommation de tabac, âge, couche sociale, etc.—le risque relatif (RR) de IM augmente de manière significative et constante avec le gêne causé par le bruit au lieu de travail. Pour le IM, la perception subjective du bruit vécu au lieu de travail est le deuxième facteur de risque, son importance n'étant dépassée que par le tabagisme. Les auteurs discutent l'incidence possible d'une notification exagérée de bruit gênant. Afin de calculer le risque d' IM attributable au bruit perçu au lieu de travail, des études interdisciplinaires devraient être réalisées pour examiner les liens entre les maladies cardiovasculaires et les stresseurs liés au travail, y compris l'évaluation subjective et objective du bruit.

     

Frontal versus transcorneal stimulation to induce maximal electroshock seizures or kindling in mice and rats

Frontal stimulation, i.e. electrical stimulation where electrodes are pressed on the skin of the intact frontal skull of mice or rats, may represent a more humane alternative to the widely used transcorneal stimulation to induce electroshock seizures. The aim of this work was to directly compare transcorneal and frontal stimulation in eliciting maximal electroshock-induced seizures (MES) in mice and the anticonvulsant effect of carbamazepine (CBZ) and phenytoin (PHT) on thus produced seizures. In addition, we stimulated mice and rats repeatedly via transcorneal and frontal electrodes to see whether kindling is produced by this procedure. Two electroshock tests were used in mice, i.e. maximal electroshock seizure threshold (MEST) test and MES generated by supramaximal stimulation (50 mA). Frontal stimulation resulted in lower convulsive threshold than in the case of corneal stimulation. Both CBZ and PHT produced dose-dependent increases in seizure threshold for both sites of stimulation, i.e. transcorneal and frontal. As regards type of electrodes, higher doses of PHT were required to increase seizure threshold in the case of frontal than transcorneal stimulation. Supramaximal stimulation (50 mA) yielded comparable ED₅₀ values regardless of the site of stimulation. Furthermore, once-daily stimulation of mice, regardless of the placement of electrodes, did not induce any changes in convulsive threshold. We also attempted to kindle mice and rats via corneal and frontal electrodes by repetitive electrical stimulation using currents which initially did not produce generalized clonic seizures. Mice were stimulated once daily for 2 s with 3 mA (corneal electrodes) or 2 mA (frontal electrodes) and rats were stimulated twice daily for 4 s at 8 mA (corneal electrodes) or 5 mA (frontal electrodes). With corneal stimulation in rats there was a clear progression of kindling development which was not the same in nature when compared with corneally-stimulated mice. Frontal stimulation did not produce kindling. Moreover, corneal stimulation was better tolerated by rats, while in mice high mortality was seen after either method of current delivery. Our data indicate that frontal electrodes can be used as an alternative to transcorneal stimulation to produce MES by supramaximal or threshold current intensities as screening procedures in antiepileptic drug (AED) development. Nevertheless, this type of stimulation cannot be used to produce minimal electroshock seizures and seems not to be useful to produce kindling in rats and mice.     

Role of DAT‐SPECT in the diagnostic work up of Parkinsonism

The diagnosis of idiopathic Parkinson's disease (PD) can be achieved with high degrees of accuracy in cases with full expression of classical clinical features. However, diagnostic uncertainty remains in early disease with subtle or ambiguous signs. Functional imaging has been suggested to increase the diagnostic yield in parkinsonian syndromes with uncertain clinical classification. Loss of striatal dopamine nerve terminal function, a hallmark of neurodegenerative Parkinsonism, is strongly related to decreases of dopamine transporter (DAT) density, which can be measured by single photon emission computed tomography (SPECT). The use of DAT‐SPECT facilitates the differential diagnosis in patients with isolated tremor symptoms not fulfilling PD or essential tremor criteria, drug‐induced, psychogenic and vascular Parkinsonism as well as dementia when associated with Parkinsonism. This review addresses the value of DAT‐SPECT in early differential diagnosis, and its potential as a screening tool for subjects at risk of developing PD as well as issues around the assessment of disease progression. © 2007 Movement Disorder Society     

Das kleinzellige Bronchialkarzinom – neue Entwicklungen nach ASCO 2007

Wiener Medizinische Wochenschrift - Aggressives Tumorwachstum, frühe Metastasierung und hohe Assoziation mit intensivem Nikotinkonsum sind die Charakteristika des kleinzelligen...