Cognitive impairment in Alzheimer's disease FAD4T mouse model: Synaptic loss facilitated by activated microglia via C1qA.

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder characterized by cognitive dysfunction. The connection between neuroinflammation and abnormal synaptic function in AD is recognized, but the underlying mechanisms remain unclear. In this study, we utilized a mouse model of AD, FAD4T mice aged 6-7 months, to investigate the molecular changes affecting cognitive impairment. Behavior tests showed that FAD4T mice exhibited impaired spatial memory compared with their wild-type littermates. Immunofluorescence staining revealed the presence of Aß plaques and abnormal glial cell activation as well as changes in microglial morphology in the cortex and hippocampus of FAD4T mice. Synaptic function was impaired in FAD4T mice. Patch clamp recordings of hippocampal neurons revealed reduced amplitude of miniature excitatory postsynaptic currents. Additionally, Golgi staining showed decreased dendritic spine density in the cortex and hippocampus of FAD4T mice, indicating aberrant synapse morphology. Moreover, hippocampal PSD-95 and NMDAR1 protein levels decreased in FAD4T mice. RNA-seq analysis revealed elevated expression of immune system and proinflammatory genes, including increased C1qA protein and mRNA levels, as well as higher expression of TNF-α and IL-18. Taken together, our findings suggest that excessive microglia activation mediated by complement factor C1qA may contribute to aberrant synaptic pruning, resulting in synapse loss and disrupted synaptic transmission, ultimately leading to AD pathogenesis and behavioral impairments in the FAD4T mouse model. Our study provides valuable insights into the underlying mechanisms of cognitive impairments and preliminarily explores a potentially effective treatment approach targeting on C1qA for AD.

Trends and frontiers of atmospheric duct research based on CiteSpace and deep learning.

The research of evaporation duct is of fundamental importance in the radar and signal communication industry. Particularly, in a real atmosphere environment, most of the radar holes cannot be corrected in time because of the persistent evaporation duct phenomenon. Thus, conducting evaporation duct research is a major concern of both academic and industrial communities. However, there is no descriptive research on the mobile communication in the marine and atmospheric environment. Numerous scholars and institutions have integrated atmospheric duct into multidisciplinary knowledge overview of the atmospheric duct in the existing published articles. The objective of this article is to explore the focus and status of atmospheric duct in-depth investigation and to grasp the frontiers and prospects of atmospheric duct research. A visual presentation of co-citation was adopted to realize the influence of authors, contributing institutions, keyword research hotspots, and frontier research based on co-citation network analysis. In addition, to identify the direction of atmospheric duct more accurately, the deep learning algorithm was adopted to conduct a comprehensive analysis of the future development trend of atmospheric duct.