LPS mediated neuronal c-Fos activation: whole-brain mapping, site and time effect in intoxicated mice

Lipopolysaccharide (LPS; a bacterial endotoxin) treatment causes acute inflammatory conditions. Acute inflammation causes the brain to activate neurons in some brain nuclei known as circumventricular organs. The c-Fos immunoreaction could be used to assess this neural activity. The current study aimed to check the activated neurons in time and site effect during toxicity and inflammation induced by LPS. The c-Fos antibody immunofluorescence labeling was checked at one, three, and six hours after LPS intoxication. Moreover, a retrograde viral tracing approach was employed to verify the neuronal connections among certain brain nuclei that were activated. The results indicated the activation of several brain nuclei in the hippocampus, epithalamus, thalamus, hypothalamus, basal ganglia, midbrain, and medulla oblongata. The type of brain nuclei and the number of neurons that were activated in relation to the duration of acute inflammation were clearly different. Furthermore, this research demonstrated that these active brain nuclei were connected neuronally. Ultimately, acute inflammatory responses induced by LPS treatment activated dorsal raphe serotonergic neurons. Twenty-two brain nuclei were shown to be involved in the neuroinflammatory response via whole-brain mapping. One hour after LPS administration, neurons in the dorsomedial hypothalamic nucleus (DM), lateral septal nucleus (LS), and solitary tract nucleus (SOL) were significantly activated. However, the sensory circumventricular organs (CVOs) were activated three hours after LPS treatment. It was also demonstrated that dorsal raphe serotonergic neurons play a vital role in the body's reaction to acute inflammation. This study confirmed the involvement of dorsal raphe serotonergic neurons in response to acute inflammation and toxicity induced by LPS.