Accumulation of amyloid-beta (Abeta) into senile plaques in Alzheimer's disease (AD) is a hallmark neuropathological feature of the disorder, which likely contributes to alterations in neuronal structure and function. Recent work has revealed changes in neurite architecture associated with plaques and functional changes in cortical signaling in amyloid precursor protein (APP) expressing mouse models of AD. Here we developed a method using gene transfer techniques to introduce green fluorescent protein (GFP) into neurons, allowing the investigation of neuronal processes in the vicinity of plaques. Multiphoton imaging of GFP-labeled neurons in living Tg2576 APP mice revealed disrupted neurite trajectories and reductions in dendritic spine density compared with age-matched control mice. A profound deficit in spine density (approximately 50%) extends approximately 20 mum from plaque edges. Importantly, a robust decrement (approximately 25%) also occurs on dendrites not associated with plaques, suggesting widespread loss of postsynaptic apparatus. Plaques and dendrites remained stable over the course of weeks of imaging. Postmortem analysis of axonal immunostaining and colocalization of synaptophysin and postsynaptic density 95 protein staining around plaques indicate a parallel loss of presynaptic and postsynaptic partners. These results show considerable changes in dendrites and dendritic spines in APP transgenic mice, demonstrating a dramatic synaptotoxic effect of dense-cored plaques. Decreased spine density will likely contribute to altered neural system function and behavioral impairments observed in Tg2576 mice.
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http://dx.doi.org/10.1523/JNEUROSCI.1879-05.2005 | DOI Listing |
J Ethnopharmacol
January 2025
School of Basic Medical Sciences, Shanxi University of Chinese Medicine, Jinzhong, Shanxi, 030619; Shanxi Provincial Key Laboratory of TCM Encephalopathy; National International Joint Research Center for Molecular Traditional Chinese Medicine. Electronic address:
Ethnopharmacological Relevance: Dihuang Drink (DHD), formulated by Liu Hejian during the Yuan Dynasty, is listed as one of the first ancient classical prescriptions by the National Medical Products Administration of China. It is commonly used for the prevention and treatment of Alzheimer's disease (AD). This study further investigates the therapeutic effects and potential mechanisms of DHD in AD.
View Article and Find Full Text PDFPrenat Diagn
January 2025
Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria.
Objective: To apply a network medicine-based approach to analyze the phenome of the prenatal fetal MRI and biometric findings in the Chiari II malformation (CM II) to detect specific patterns and co-occurrences.
Method: A single-center retrospective review of fetal MRI scans obtained in fetuses with CM II was performed. Co-occurrence analysis was utilized to generate a phenotypic comorbidity matrix and visualized by Gephi software.
Redox Biol
December 2024
Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, 300052, China; Tianjin Research Institute of Anesthesiology, Tianjin, 300052, China. Electronic address:
Chronic itch which is primarily associated with dermatologic, systemic, or metabolic disorders is often refractory to most current antipruritic medications, thus highlighting the need for improved therapies. Oxidative damage is a novel determinant of spinal pruriceptive sensitization and synaptic plasticity. The resolution of oxidative insult by molecular hydrogen has been manifested.
View Article and Find Full Text PDFCalcif Tissue Int
January 2025
Internal Medicine Division, Federal University of Parana (UFPR), Curitiba, PR, Brazil.
Patients with radiographic axial spondyloarthritis (r-axSpA) experience a higher prevalence of fragility fractures, though the pathophysiology of osteoporosis associated with this disease remains poorly understood. The objective of this study was to evaluate the histomorphometric data in r-axSpA patients. Male r-axSpA patients up to 55 years old were enrolled in this cross-sectional study.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Michigan, Ann Arbor, MI, USA.
Background: Alzheimer's disease (AD) is the leading cause of dementia worldwide. The recent announcement that lecanemab, a monoclonal antibody targeting amyloid-b, can slow down cognitive decline in AD is a great step forward in the battle against the disease. However, the modest success achieved in the clinical trial speak to the need for developing additional pharmaceutical approaches to target other key features of AD.
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