Intraneuronal APP and extracellular Aβ independently cause dendritic spine pathology in transgenic mouse models of Alzheimer’s disease

Abstract Alzheimer’s disease (AD) is thought to be caused by accumulation of amyloid-β protein (Aβ), which is a cleavage product of amyloid precursor protein (APP). Transgenic mice overexpressing APP have been used to recapitulate amyloid-β pathology. Among them, APP23 and APPswe/PS1deltaE9 (deltaE9) mice are extensively studied. APP23 mice express APP with Swedish mutation and develop amyloid plaques late in their life, while cognitive deficits are observed in young age. In contrast, deltaE9 mice with mutant APP and mutant presenilin-1 develop amyloid plaques early but show typical cognitive deficits in old age. To unveil the reasons for different progressions of cognitive decline in these commonly used mouse models, we analyzed the number and turnover of dendritic spines as important structural correlates for learning and memory. Chronic in vivo two-photon imaging in apical tufts of layer V pyramidal neurons revealed a decreased spine density in 4–5-month-old APP23 mice. In age-matched deltaE9 mice, in contrast, spine loss was only observed on cortical dendrites that were in close proximity to amyloid plaques. In both cases, the reduced spine density was caused by decreased spine formation. Interestingly, the patterns of alterations in spine morphology differed between these two transgenic mouse models. Moreover, in APP23 mice, APP was found to accumulate intracellularly and its content was inversely correlated with the absolute spin...
Source: Acta Neuropathologica - Category: Neurology Source Type: research

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CONCLUSION: Prevalence of antibiotic use was high not only versus other hospitals in the region but globally including Africa, coupled with significant evidence of sub-optimal prescribing. Swift action is needed to improve future prescribing to reduce AMR. One or two areas should initially be targeted for quality improvement including development of local guidelines, documentation of antibiotic indications and/or stop/review dates. PMID: 33034234 [PubMed - as supplied by publisher]
Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
Authors: Rombauts A, Abelenda-Alonso G, Cuervo G, Gudiol C, Carratalà J Abstract INTRODUCTION: Despite adequate antibiotic coverage, community-acquired pneumonia (CAP) remains a leading cause of hospitalization and mortality worldwide. It induces both a local pulmonary and a systemic inflammatory response, particularly significant in severe cases. The intensity of the dysregulated host response varies from patient to patient and has a negative impact on survival and other outcomes. AREAS COVERED: This comprehensive review summarizes the pathophysiological aspects of the inflammatory response in CAP, brie...
Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
Authors: Hammerschlag MR, Sharma R Abstract INTRODUCTION: Azithromycin was recommended as the first-line therapeutic regimen for treatment of genital infections in men and women by the Centers for Disease Control in 1998. A series of studies of azithromycin for treatment of rectal chlamydial infection in men who have sex with men (MSM) found that azithromycin was significantly less effective than doxycycline. AREAS COVERED: Literature on treatment of rectal C. trachomatis from 2000 through May 2020 was searched using PubMed. Retrospective and observational studies were identified documenting the frequency and t...
Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
Authors: Reissier S, Cattoir V Abstract INTRODUCTION: Streptogramins (pristinamycin and quinupristin-dalfopristin) can be interesting options for the treatment of infections due to Gram-positive cocci, especially multidrug-resistant isolates. AREAS COVERED: This review provides an updated overview on structural and activity characteristics, mechanisms of action and resistance, pharmacokinetic/pharmacodynamic and clinical use of streptogramins. EXPERT OPINION: The streptogramin antibiotics act by inhibition of the bacterial protein synthesis. They are composed of two chemically distinct compounds, namely typ...
Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
Publication date: 15 February 2021Source: Journal of Hazardous Materials, Volume 404, Part BAuthor(s): Ping He, Yi Zhang, Xinyi Zhao, Jie Wei, Tianhong Xu, Jiang Wu, Naichao Chen
Source: Journal of Hazardous Materials - Category: Environmental Health Source Type: research
Publication date: 15 February 2021Source: Journal of Hazardous Materials, Volume 404, Part BAuthor(s): Jing Li, Haotian Li, Dongdong Lin, Muyi Li, Quansheng Wang, Song Xie, Yuming Zhang, Fengsong Liu
Source: Journal of Hazardous Materials - Category: Environmental Health Source Type: research
Publication date: 15 February 2021Source: Journal of Hazardous Materials, Volume 404, Part BAuthor(s): Yanhua Liu, Yang Li, Shanshan Dong, Lu Han, Ruixin Guo, Yourong Fu, Shenghu Zhang, Jianqiu Chen
Source: Journal of Hazardous Materials - Category: Environmental Health Source Type: research
Publication date: 15 February 2021Source: Journal of Hazardous Materials, Volume 404, Part AAuthor(s): Cheng Han, Yinping Zhang, Marc Redmile-Gordon, Huan Deng, Zhenggui Gu, Qiguo Zhao, Fang Wang
Source: Journal of Hazardous Materials - Category: Environmental Health Source Type: research
Publication date: 15 February 2021Source: Journal of Hazardous Materials, Volume 404, Part AAuthor(s): Taesik Go, Jihwan Kim, Sang Joon Lee
Source: Journal of Hazardous Materials - Category: Environmental Health Source Type: research
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Source: Journal of Hazardous Materials - Category: Environmental Health Source Type: research
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