Long-term LPS systemic administration leads to memory impairment and disturbance in astrocytic homeostasis
NEUROTOXICOLOGY(2023)
摘要
Dementia is the most prevalent neurodegenerative disorder, characterized by progressive loss of memory and cognitive function. Inflammation is a major aspect in the progression of brain disorders, and inflammatory events have been associated with accelerated deterioration of cognitive function. In the present work, we investigated the impact of low-grade repeated inflammation stimuli induced by lipopolysaccharide (LPS) in hippocampal function and spatial memory. Adult male Wistar rats received a weekly injection of LPS (500 ug/kg) for sixteen weeks, eliciting systemic inflammation. Animals submitted to LPS presented impaired spatial memory and neuroinflammation. While neuronal synaptic markers such as synaptophysin and PSD-95 were unaltered, critical aspects of astrocyte homeostatic functions, such as glutamate uptake and glutathione content, were reduced. Also, glucose uptake and astrocyte lactate transporters were altered, suggesting a disturbance in the astrocyteneuron coupling. Our present work demonstrates that long-term repeated systemic inflammation can lead to memory impairment and hippocampal metabolic disorders, especially regarding astrocyte function.
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关键词
Astrocytes,Lipopolysaccharide,Memory,Hippocampus,Low-grade repeated inflammation,Neuroinflammation
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