Acute systemic LPS-mediated inflammation induces lasting changes in mouse cortical neuromodulation and behavior

Area of Science:

• Neuroscience
• Immunology
• Pharmacology

Background:

• Systemic lipopolysaccharide (LPS) induces neuroinflammation linked to sickness behavior.
• Unchecked neuroinflammation can lead to self-perpetuating, long-term neurodegenerative processes.

Purpose of the Study:

• To investigate the long-term effects of a single systemic LPS injection on neuromodulator function and behavior in mice.
• To determine if acute inflammation can initiate chronic neurodegenerative pathways.

Main Methods:

• Mice received a single systemic LPS injection.
• Electrophysiological analysis of neuromodulator effects (acetylcholine, norepinephrine, serotonin) was performed 5 months post-injection.
• Behavioral tests included novel object recognition, open field test, and tail suspension test.
• Acetylcholinesterase activity was measured.

Main Results:

• LPS-treated mice exhibited reduced cortical inhibition and altered acetylcholine neuromodulation.
• Memory performance was impaired in the novel object recognition test.
• No significant changes were observed in anxiety or despair behaviors.
• Increased acetylcholinesterase activity was noted in LPS-treated mice.

Conclusions:

• A single systemic LPS event can induce lasting neurophysiological and cognitive changes.
• Increased acetylcholinesterase activity suggests impaired acetylcholine signaling, potentially contributing to cognitive deficits.
• These findings highlight the potential for acute inflammation to trigger long-term neurodegeneration.