Impaired Decision Making and Loss of Inhibitory-Control in a Rat Model of Huntington Disease

Cognitive deficits associated with Huntington disease (HD) are generally dominated by executive function disorders often associated with disinhibition and impulsivity/compulsivity. Few studies have directly examined symptoms and consequences of behavioral disinhibition in HD and its relation with decision-making. To assess the different forms of impulsivity in a transgenic model of HD (tgHD rats), two tasks assessing cognitive/choice impulsivity were used: risky decision-making with a rat gambling task (RGT) and intertemporal choices with a delay discounting task (DD). To assess waiting or action impulsivity the differential reinforcement of low rate of responding task (DRL) was used. In parallel, the volume as well as cellular activity of the amygdala was analyzed. In contrast to WT rats, 15 months old tgHD rats exhibited a poor efficiency in the RGT task with difficulties to choose advantageous options, a steep DD curve as delays increased in the DD task and a high rate of premature and bursts responses in the DRL task. tgHD rats also demonstrated a concomitant and correlated presence of both action and cognitive/choice impulsivity in contrast to wild type (WT) animals. Moreover, a reduced volume associated with an increased basal cellular activity of the central nucleus of amygdala indicated a dysfunctional amygdala in tgHD rats, which could underlie inhibitory dyscontrol. In conclusion, tgHD rats are a good model for impulsivity disorder that could be used more widely to identify potential pharmacotherapies to treat these invasive symptoms in HD

Transglutaminase 6 is colocalized and interacts with mutant Huntingtin in Huntington disease rodent animal models

Mammalian transglutaminases (TGs) catalyze calcium-dependent irreversible posttranslational modifications of proteins and their enzymatic activities contribute to the pathogenesis of several human neurodegenerative diseases. Although different transglutaminases are found in many different tissues, the TG6 isoform is mostly expressed in the CNS. The present study was embarked on/undertaken to investigate expression, distribution and activity of transglutaminases in Huntington disease transgenic rodent models, with a focus on analyzing the involvement of TG6 in the age- and genotype-specific pathological features relating to disease progression in HD transgenic mice and a tgHD transgenic rat model using biochemical, histological and functional assays. Our results demonstrate the physical interaction between TG6 and (mutant) huntingtin by co-immunoprecipitation analysis and the contribution of its enzymatic activity for the total aggregate load in SH-SY5Y cells. In addition, we identify that TG6 expression and activity are especially abundant in the olfactory tubercle and piriform cortex, the regions displaying the highest amount of mHTT aggregates in transgenic rodent models of HD. Furthermore, mHTT aggregates were colocalized within TG6-positive cells. These findings point towards a role of TG6 in disease pathogenesis via mHTT aggregate formation

Automated operant assessments of Huntington's Disease mouse models

Huntington’s disease (HD) presents clinically with a triad of motor, cognitive, and psychiatric symptoms. Cognitive symptoms often occur early within the disease progression, prior to the onset of motor symptoms, and they are significantly burdensome to people who are affected by HD. In order to determine the suitability of mouse models of HD in recapitulating the human condition, these models must be behaviorally tested and characterized. Operant behavioral testing offers an automated and objective method of behaviorally profiling motor, cognitive, and psychiatric dysfunction in HD mice. Furthermore, operant testing can also be employed to determine any behavioral changes observed after any associated interventions or experimental therapeutics. We here present an overview of the most commonly used operant behavioral tests to dissociate motor, cognitive, and psychiatric aspects of mouse models of HD

Improved acceptance of electronic media to support the introductory remarks in the anatomical dissection course

The anatomical dissection course takes place in the first year of preclinical training at the Medical School of Hannover. In two consecutive years, one out of eight groups (each about 40 students) received an intensified introduction supported by electronic slides and videos at the beginning of each day of dissection. In both years, the new introduction was evaluated. In the second year, modifications resulting from the first evaluation were incorporated. In both years, the students rated the new approach very positively. These results are discussed in respect to educating future medical doctors and to being well prepared for the preclinical exams.Der Präparierkurs wird an der Medizinischen Hochschule Hannover im ersten und zweiten vorklinischen Semester durchgeführt. In zwei aufeinander folgenden Jahren wurde in jeweils einer von insgesamt acht Gruppen mit etwa 40 Studierenden immer unmittelbar vor Kursbeginn eine intensivierte Einleitung mit elektronischem Bildmaterial und Filmen durchgeführt. In beiden Jahren wurden die Einführungen evaluiert. Aus den Ergebnissen der ersten Befragung ableitbare Veränderungen wurden im zweiten Jahr bereits eingearbeitet. Die neue Vorgehensweise wurde in beiden Jahren sehr positiv bewertet. Anhand der Resultate werden Möglichkeiten einer optimierten Durchführung des Präparierkurses im Hinblick auf die Ausbildung zum Arzt und als Vorbereitung auf die ärztliche Vorprüfung diskutiert

External arguments in the multiple-spiral medallions of the Mandelbrot set

10 pages, 10 figures.-- PACS nr.: 05.45.Df.-- Printed version published on Jun 2006.The discs of a small copy of the Mandelbrot set \mathcal{M} have the same kinds of antennas or shrubs as the discs of \mathcal{M}, with the obvious difference that the shrubs of the small copy are “attached” to tendrils. Beautiful tendril decorations exist, known as multiple-spiral medallions, and these medallions are formed by an infinite number of baby Mandelbrot sets. Computer graphics and the external arguments theory provide two invaluable tools to study the structure of these decorations. In this work, we conjecture that the baby Mandelbrot sets of a multiple-spiral medallion have a "parent" and a "gene". This conjecture allows us to write the binary expansions of the external arguments of the baby Mandelbrot sets in an easy and structured way.This work was supported by Ministerio de Educación y Ciencia of Spain, Research Grant SEG2004-02418.Peer reviewe

Regional and subtype selective changes of neurotransmitter receptor density in a rat transgenic for the Huntington's disease mutation

Huntington's disease (HD) is an autosomal dominantly inherited progressive neurodegenerative disorder caused by a CAG/polyglutamine repeat expansion in the gene encoding the huntingtin protein. We have recently generated a rat model transgenic for HD, which displays a slowly progressive phenotype resembling the human adult-onset type of disease. In this study we systematically assessed the distribution and density of 17 transmitter receptors in the brains of 2-year-old rats using quantitative multi-tracer autoradiography and high-resolution positron emission tomography. Heterozygous animals expressed increased densities of M(2) acetylcholine (increase of 148 +/- 16% of controls; p > 0.001; n = 7), nicotine (increase of 149 +/- 16% of controls; p > 0.01; n = 6), and alpha(2) noradrenergic receptors (increase of 141 +/- 15% of controls; p > 0.001; n = 6), respectively. Densities of these receptors were decreased in homozygous animals. Decreases of receptor density in both hetero- and homozygous animals were found for M1 acetylcholine, 5-HT 2A serotonin, A 2A adenosine, D1 and D2 dopamine, and GABA(A) receptors, respectively. Other investigated receptor systems showed small changes or were not affected. The present data suggest that the moderate increase of CAG/polyglutamine repeat expansions in the present rat model of Huntington's disease is characterized by subtype-selective and region-specific changes of neuroreceptor densities. In particular, there is evidence for a contribution of predominantly presynaptically localized cholinergic and noradrenergic receptors in the response to Huntington's disease pathology