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

Area of Science:

• Neuroscience
• Immunology
• Toxicology

Background:

• Lipopolysaccharide (LPS) is a bacterial endotoxin that induces acute inflammatory conditions.
• Acute inflammation activates specific brain nuclei, including circumventricular organs.
• c-Fos immunoreaction is a reliable marker for assessing neural activity during inflammation.

Purpose of the Study:

• To investigate the temporal and spatial effects of LPS-induced neural activation.
• To map the neuronal connections among activated brain nuclei.
• To elucidate the role of dorsal raphe serotonergic neurons in LPS-induced neuroinflammation.

Main Methods:

• Administered LPS to induce acute inflammation and toxicity.
• Utilized c-Fos antibody immunofluorescence labeling at 1, 3, and 6 hours post-LPS.
• Employed retrograde viral tracing to identify neuronal connections.

Main Results:

• LPS activated numerous brain nuclei across the hippocampus, epithalamus, thalamus, hypothalamus, basal ganglia, midbrain, and medulla oblongata.
• Neural activation patterns varied significantly with the duration of inflammation.
• Demonstrated neuronal connectivity between activated brain nuclei, highlighting 22 involved nuclei in the neuroinflammatory response.
• Identified early activation (1 hour) in the dorsomedial hypothalamic nucleus, lateral septal nucleus, and solitary tract nucleus, with sensory circumventricular organs activated at 3 hours.
• Confirmed the crucial role of dorsal raphe serotonergic neurons in responding to LPS-induced inflammation and toxicity.

Conclusions:

• LPS-induced acute inflammation leads to widespread, time-dependent neural activation in specific brain regions.
• Dorsal raphe serotonergic neurons are integral to the neuroinflammatory response to LPS.
• This study provides a comprehensive whole-brain map of neural circuits involved in LPS-induced neuroinflammation.