18 research outputs found
Automated behavioral phenotyping of inbred mouse strains and mouse models of Alzheimer disease
No full textBehavioral characterization of various mouse strains created as models for human diseases such as Alzheimer disease requires robust phenotyping methods. Previous work on inbred mouse strains has shown that some of the widely used behavioral methods yield inconsistent results across laboratories, in spite of standardization efforts. One approach to minimize experimenter induced variability relies on development of automated methods.The aims of this thesis were to evaluate an automated device - the IntelliCage - which enables behavioral testing of group-housed mice. In a multi-center study, inter- laboratory consistency of behavioral measurements in IntelliCage was evaluated [study I]. Three strains of mice: C57BL/6NCrl (B6), DBA/2NCrl (D2) and (C57BL/6 x DBA/2) F1/NCrl (C6D2F1) were tested simultaneously in four laboratories (n=78/lab). No statistically significant interaction effect of Laboratory x Strain was obtained, indicating that strains were consistently ranked across laboratories. Significant Laboratory effects were obtained for several Activity and Learning variables due to uncontrolled local factors. Phenotypically, the mouse strains were not discriminated during the initial exploratory phase. During the following adaptation phases the B6 mice made more visits to IntelliCage corners than the D2 mice. For unconditioned phases, the visit number for F1 mice was between that of the inbred strains. For conditioned phases F1 mice performed the smallest number of visits. B6 mice discriminated best following place learning and D2 were best at re-learning the task. F1 ranked last on both place learning and reversal measures of learning.Using the same multi-center study design and the same mouse strains, we evaluated the effect of additional components (add-ons) availability on IntelliCage measures [study II]. In the enriched condition (IntelliMaze) access to additional space was made through the “SocialBox” and “AnimalGate” add-on devices. The unconditioned activity during adaptation dark phases was reduced in the presence of add-ons. During the place conditioning paradigms, the overall number of trials needed to reach the learning criterion, was lower in the presence of add-ons. The strain ranks for activity measures were consistent with the results of study I.Dissociation in cognitive abilities of B6 and D2 mice has been proposed as a natural model to study hippocampal (dys)function. Behavioral predictive validity of animal models for Alzheimer disease is implied by impairments in hippocampal dependent tasks.In study III, a double transgenic Amyloid precursor protein model of Alzheiemer disease, (the tg-ArcSwe) was tested longitudinally in the IntelliCage. Lower body weight was found throughout the adult life-span of the tg-APPArcSwe mice. Lower activity counts were seen at 4 month of age, but not at 14 months. A deficit in extinguishing place preference for a previously rewarded corner at 4 month was shown. At 14 months the tg-APPArcSwe mice were impaired in a passive avoidance test in the IntelliCage. During the training phase of the passive avoidance test the behavior (preference for the punished corner) of tg-ArcSwe was found to moderately and inversely correlate with the level of CALB immunoreactivity in the polymorphic layer of the DG.Finally, the effects of IntelliCage exposure as well as relationships between variables obtained during IntelliCage testing and Elevated Plus Maze, Open field, Rotarod, Morris Water Maze and Fear conditioning were explored [study IV]. We found that only a limited amount of variance in the conventional tests could be accounted for by IntelliCage variables.In conclusion we have shown that mouse strains can be discriminated using the IntelliCage. Similarly, the behavior of tg-ArcSwe and non-tg mice was dissociated by this metholodogy. Although some degree of correlation was found between the results of conventional studies and IntelliCage variables, only a small part of the variance in conventional studies was explained by variables obtained in the IntelliCage.List of scientific papersI. Consistent behavioral phenotype differences between inbred mouse strains in the IntelliCage. S. Krackow, E. Vannoni, A. Codita, A. H. Mohammed, F. Cirulli, I. Branchi, E. Alleva, A. Reichelt, A. Willuweit, V. Voikar, G. Colacicco, D. P.Wolfer, J. U. F. Buschmann, K. Safi, H.-P. Lipp. Genes Brain Behav. 2010; 9:722-31. https://doi.org/10.1111/j.1601-183X.2010.00606.x II. Effects of spatial and cognitive enrichment on activity pattern and learning performance in three strains of mice in the IntelliMaze. A. Codita, A. H. Mohammed, A. Willuweit, A. Reichelt, E. Alleva, I. Branchi, F. Cirulli, G. Colacicco, V. Voikar, D.P. Wolfer, F.J.U. Buschmann, H-P Lipp, E. Vannoni, S. Krackow. [Submitted]III. Impaired behavior of female tg-ArcSwe APP mice in the IntelliCage: A longitudinal study. A. Codita, A.Gumucio, L. Lannfelt, P. Gellerfors, B. Winblad, A. H. Mohammed, L.N.G. Nilsson. Behav Brain Res. 2010; 215:83-94. https://doi.org/10.1016/j.bbr.2010.06.034 IV. Influence of IntelliCage testing on subsequent behavioral measures; Intra-test and inter-test relationships between automated measures of home cage behavior and behavioral measures from conventional tests. A. Codita, M. Mitrovic, A. Horvath, R. Rabl, B. Hutter–Paier, M. Windisch, A. H. Mohammed. [Manuscript]</p
Alterations in brain leptin signalling in spite of unchanged CSF leptin levels in Alzheimer’s disease
No full textSeveral studies support the relation between leptin and Alzheimer’s disease (AD). We show that leptin levels in CSF are unchanged as subjects progress to AD. However, in AD hippocampus, leptin signalling was decreased and leptin localization was shifted, being more abundant in reactive astrocytes and less in neurons. Similar translocation of leptin was found in brains from Tg2576 and apoE4 mice. Moreover, an enhancement of leptin receptors was found in hippocampus of young Tg2576 mice and in primary astrocytes and neurons treated withAb1-42. In contrast, old Tg2576 mice showed decreased leptin receptors levels. Similar findings to those seen in Tg2576 mice were found in apoE4, but not in apoE3 mice. These results suggest that leptin levels are intact, but leptin signalling is impaired in AD. Thus, Ab accumulation and apoE4 genotype result in a transient enhancement of leptin signalling that might lead to a leptin resistance state over time
H1N1 influenza virus induces narcolepsy-like sleep disruption and targets sleep-wake regulatory neurons in mice
No full textAn increased incidence in the sleep-disorder narcolepsy has been associated with the 2009-2010 pandemic of H1N1 influenza virus in China and with mass vaccination campaigns against influenza during the pandemic in Finland and Sweden. Pathogenetic mechanisms of narcolepsy have so far mainly focused on autoimmunity. We here tested an alternative working hypothesis involving a direct role of influenza virus infection in the pathogenesis of narcolepsy in susceptible subjects. We show that infection with H1N1 influenza virus in mice that lack B and T cells (Recombinant activating gene 1-deficient mice) can lead to narcoleptic-like sleep-wake fragmentation and sleep structure alterations. Interestingly, the infection targeted brainstem and hypothalamic neurons, including orexin/hypocretin-producing neurons that regulate sleep-wake stability and are affected in narcolepsy. Because changes occurred in the absence of adaptive autoimmune responses, the findings show that brain infections with H1N1 virus have the potential to cause per se narcoleptic-like sleep disruption
Las Observaciones de Pedro Henríquez Ureña y la historia del castellano en Panamá
No full textIn his proposal for the zoning of American Spanish from 1921, Pedro Henríquez Ureña does not mention Panama at any time, although, in a later work, he associates the Panamanian modality with Colombia, a fact motivated by political reasons. To delimit the five large dialectal zones, the author uses, above all, phonetic-phonological data, aspects also brought up in more recent works, which relate the Panamanian variety with the Caribbean macrozone. Despite these works and the evidence of this linguistic affiliation, reconstructing the phoneticphonological component of Panamanian Spanish in the past requires facing an almost total research vacuum. For this reason, the present work aims to study some phonetic-phonological phenomena, relevant for the Panamanian linguistic characterization, in the documentation of the 16th century in order to establish the historical basis of these features in Panamanian territory. Our data show that the presence of traits ascribed to the southern peninsular modalities in the Panamanian variety, from its origins, is undeniable, although other factors must be taken into account in its conformation.En su propuesta de zonificación del español americano de 1921, Pedro Henríquez Ureña no menciona en ningún momento Panamá, si bien, en un trabajo más tardío, vincula la modalidad panameña con Colombia, motivado por razones políticas. Para delimitar las cinco grandes zonas dialectales, el autor se sirve, sobre todo, de datos fonético-fonológicos, que se sacan a colación también en investigaciones más recientes, al relacionar la variedad panameña con la macrozona caribeña. A pesar de estos trabajos y de la evidencia de esta filiación lingüística, tratar de reconstruir el componente fonético-fonológico del español panameño en el pasado exige enfrentarse a un vacío investigador casi total. Por ello, el presente artículo se plantea como objetivo estudiar algunos fenómenos fonético-fonológicos, relevantes para la caracterización lingüística panameña, en la documentación del siglo XVI a fin de poder asentar la base histórica de estos rasgos en territorio panameño. Nuestros datos muestran que la presencia de rasgos adscritos a las modalidades peninsulares meridionales en la variedad panameña, desde sus orígenes, es innegable, aunque hay que tener en cuenta otros factores en su conformación
Association between severe periodontitis and dislypidemia
No full textRezumat.
Scopul studiului il reprezinta evaluarea unei posibile corelatii intre parodontitele cronice stadiul sever si nivelul lipidelor serice.
Materiale si metoda: Un lot de 59 de pacienti cu varsta intre 45-54 de
ani carora li s-au efectuat anamneza si examenul clinic, precum si analize
generale (colesterol si trigliceride).
Rezultate: 44,8% dintre pacienti prezentau nivele crescute ale trigliceridelor (valoare medie 212 mg/dl), iar 55,17% dintre pacienti prezentau un
nivel crescut al colesterolului total (valoare medie 256mg/dl).
Concluzii: Exista o corelatie intre parodontitele severe si nivelele serice
crescute ale colesterolului si trigliceridelor, fapt ce trebuie sa atraga atentia
medicului dentist.Summary.
The purpose of the study is the evaluation of a possible correlation between severe stage chronic periodontitis and the level of serum lipids.
Materials and method: A sample of 59 patients, between 45 - 54 years
old, who underwent clinical dental examination and a set of blood analysis
(cholesterol and triglycerides).
Results: 44,8% of the patients exhibited high levels of triglycerides (median value of 212 mg/dl), and 55,17% of them exhibited a high level of total
cholesterol (median value 256mg/dl).
Conclusion: There is a relationship between severe periodontal disease
and high serum levels of cholesterol and triglycerides, a fact requires the
attention of the dentist
Impaired behavior of female tg-ArcSwe APP mice in the IntelliCage: A longitudinal study
No full textTransgenic animals expressing mutant human amyloid precursor protein (APP) are used as models for Alzheimer disease (AD). Ideally, behavioral tests improve the predictive validity of studies on animals by mirroring the functional impact of AD-like neuropathology. Learning and memory studies in APP transgenic models have been difficult to replicate. Standardization of procedures, automatization or improved protocol design can improve reproducibility. Here the IntelliCage, an automated system, was used for behavioral testing of APP female transgenic mice with both the Arctic and Swedish mutations, the tg-ArcSwe model. Protocols covering exploration, operant learning, place learning and extinction of place preference as well as passive avoidance tests were used for longitudinal characterization of behavior. Differences in exploratory activity were significant at four months of age, when plaque-free tg-ArcSwe mice visited less frequently the IntelliCage corners and initially performed fewer visits with licks compared to non-tg animals, inside the new environment. Fourteen months old tg-ArcSwe mice required a longer time to re-habituate to the IntelliCages than non-tg mice. At both ages tg-ArcSwe mice perseverated in place preference extinction test. Fourteen months old tg-ArcSwe mice were impaired in hippocampus-dependent spatial passive avoidance learning. This deficit was found to inversely correlate to calbindin-D28k immunoreactivity in the polymorphic layer of the dentate gyrus. Reduced water intake and body weight were observed in 4 months old tg-ArcSwe animals. The body weight difference increased with age. Thus behavioral and metabolic changes in the tg-ArcSwe APP model were detected using the IntelliCage, a system which provides the opportunity for standardized automated longitudinal behavioral phenotyping.</p
P4‐072: Cholesterol accumulates in the vicinity of amyloid‐beta deposits in brain tissue
No full text
