Long-term LPS systemic administration leads to memory impairment and disturbance in astrocytic homeostasis

• Published in: Neurotoxicology (Park Forest South) 2023-12, Vol.99, p.322-331
• Main Authors: Schirmbeck, Gabriel Henrique, Seady, Marina, Fróes, Fernanda Telles, Taday, Jéssica, Da Ré, Carollina, Souza, Jéssica Maria, Gonçalves, Carlos Alberto, Leite, Marina Concli
• Format: Article
• Language: English
• Subjects: Animals; Astrocytes; Hippocampus; Homeostasis; Inflammation - chemically induced; Lipopolysaccharides - toxicity; Male; Memory Disorders - metabolism; Rats; Rats, Wistar
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2023.11.009

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 astrocyte-neuron coupling. Our present work demonstrates that long-term repeated systemic inflammation can lead to memory impairment and hippocampal metabolic disorders, especially regarding astrocyte function.