PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 15869949

Abnormal APP, cholinergic and cognitive function in Ts65Dn Down's model mice.

Hyemyung Seo·Ole Isacson
View original source ↗Export metadata ↓

Abstract

We evaluated Ts65Dn Down's syndrome mice and their littermates (LM) at 1-2, 4, and 12 months of age to determine amyloid precursor protein (APP)-related cellular and biochemical changes associated with cognitive deficits. Ts65Dn mice showed cognitive deficits in the Morris water maze compared to LM mice at 4 and 12 months of age. Ts65Dn, but not LM mice, developed a septohippocampal cholinergic neuronal degeneration of choline acetyltransferase (ChAT)-positive neurons at 12 months of age. These cellular changes were compensated by increases in ChAT enzyme activity of remaining cholinergic terminals in the hippocampus. By 12 months of age, Ts65Dn mice had elevations of APP protein levels in the hippocampus compared to their LM. At this age, both Ts65Dn mice and their LM abnormally responded to cholinergic muscarinic M1 agonist treatment in terms of hippocampal APP, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) levels compared to young adult C57BL/6 mice. In summary, the Ts65Dn mice show developmental and progressive age-related behavioral deficits, hippocampal APP, and cholinergic pathology. The relatively better cognitive spatial performance in LM compared to Ts65Dn mice suggests that high APP levels combined with progressive degeneration of the cholinergic system are critical to the pathology and cognitive deficits seen in Ts65Dn mice.

Explore related subjects

Age FactorsAmyloid beta-Protein PrecursorAnalysis of VarianceAnimalsAnimals, NewbornBehavior, AnimalBlotting, WesternCell CountCholine O-AcetyltransferaseCognitionDisease Models, AnimalDown SyndromeEnzyme-Linked Immunosorbent AssayEscape ReactionFemaleGene Expression Regulation, DevelopmentalHippocampusImmunohistochemistryMaze LearningMiceMice, TransgenicMuscarinic AgonistsReaction TimeSuccinimidesComparative StudyJournal ArticleResearch Support, Non-U.S. Gov't

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Hyemyung Seo, Ole Isacson. 2005. Abnormal APP, cholinergic and cognitive function in Ts65Dn Down's model mice.. https://doi.org/10.1016/j.expneurol.2004.11.017

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Choice of time scale and its effect on significance of predictors in longitudinal studies.

Time-to-event regression is a frequent tool in biomedical research. In clinical trials this time is usually measured from the beginning of the study. The same approach is often adopted in the analysis of longitudinal observational studies. However, in recent years there has appeared literature making a case for the use of the date of birth as a starting point, and thus utilize age as the time-to-event. In this paper, we explore different types of age-scale models and compare them with time-on-study models in terms of the estimated regression coefficients they produce. We consider six proportional hazards regression models that differ in the choice of time scale and in the method of adjusting for the years before the study. By considering the estimating equations of these models as well as numerical simulations we conclude that correct adjustment for the age at entry is crucial in reducing bias of the estimated coefficients. The unadjusted age-scale model is inferior to any of the five other models considered, regardless of their choice of time scale. Additionally, if adjustment for age at entry is made, our analyses show very little to suggest that there exists any practically meaningful difference in the estimated regression coefficients depending on the choice of time scale. These findings are supported by four practical examples from the Framingham Heart Study.

Age Factors↗
PubMed2007

True health vs response styles: exploring cross-country differences in self-reported health.

The aim of this paper is to decompose cross-national differences in self-reported general health into parts explained by differences in 'true' health, measured by diagnosed conditions and measurements, and parts explained by cross-cultural differences in response styles. The data used were drawn from the Survey of Health, Ageing and Retirement in Europe 2004 (SHARE), using information from 22 731 individuals aged 50 and over from 10 European countries. Self-rated general health shows large cross-country variations. According to their self-reports, the healthiest respondents live in the Scandinavian countries and the least healthy live in Southern Europe. Counterfactual self-reported health distributions that assume identical response styles in each country show much less variation in self-reports than factual self-reports. Danish and Swedish respondents tend to largely over-rate their health (relative to the average) whereas Germans tend to under-rate their health. If differences in reporting styles are taken into account, cross-country variations in general health are reduced but not eliminated. Failing to account for differences in reporting styles may yield misleading results.

Age Factors↗
PubMed2007

Outcome of craniofacial resection in patients 70 years of age and older.

BACKGROUND: Craniofacial resection (CFR) for patients over 70 years of age is uncommon. This study examines a cohort of 36 patients who had CFR at a single institution with the aim of reporting mortality, complications, and outcome. METHODS: Thirty-six patients 70 years of age and older were identified from a prospective database of 234 patients who had CFR at a single institution. The median age was 72 years (range, 70-87). Seventeen (47%) patients had had prior single-modality or combined treatment, which included surgery in 14 (40%), radiation in 13 (36%), and chemotherapy in 2 (6%). Thirty-five patients had a malignant tumor and 1 patient a benign tumor; 15 (42%) had high-grade, 17 (47%) intermediate-grade, and 4 (11%) low-grade pathology. The margins of resection were close or microscopically positive in 18 (50%). Adjuvant radiotherapy was given in 15 (42%) and chemotherapy in 1 (3%). Complications were classified into overall, local, central nervous system (CNS), systemic, and orbital. Overall survival (OS) and disease-specific survival (DSS) were determined using the Kaplan-Meier method. Outcomes were compared with patients less than 70 years of age. RESULTS: Postoperative mortality occurred in 6 (17%) patients and postoperative complications occurred in 23 (64%) patients. Local wound complications occurred in 11 (30%), CNS in 12 (33%), systemic in 6 (17%), and orbital in 1 (3%). Postoperative mortality and complications were significantly higher in patients 70 years of age and older compared with patients less than 70 years of age (17% versus 1.5%, p = .0005; 64% versus 36%, p = .003, respectively). With a median follow-up of 27 months (range, 1-237), the 3 year OS and DSS were significantly poorer than patients less than 70 years of age (OS: 53% versus 69%, p = .0004; DSS: 61% versus 70%, p = .01) due to increased medical comorbidity (53% versus 24%, p = .001) and poorer histology (high-, intermediate-, low-grade histology: 42%, 47%, 11% versus 26%, 47%, 27%, p = .05, respectively) in patients over 70 years of age. CONCLUSION: CFR in patients 70 years of age and older is associated with increased mortality, increased incidence of complications, and a poorer overall and disease-specific 3-year survival, compared with patients less than 70 years of age. The survival was likely due to increased medical comorbidity and adverse histology. These factors must be taken into account when considering an elderly patient for craniofacial resection.

Age Factors↗