Vortioxetine Prevents Lipopolysaccharide-Induced Memory Impairment Without Inhibiting the Initial Inflammatory...

Area of Science:

• Neuroscience
• Pharmacology
• Immunology

Background:

• Vortioxetine is a multimodal antidepressant with known cognitive and neuroprotective effects.
• Microglial cells play a crucial role in brain plasticity and cognitive function.
• Immune challenges, like lipopolysaccharide (LPS) injection, can induce sickness behavior, anhedonia, and memory impairment.

Purpose of the Study:

• To investigate the effects of vortioxetine pretreatment on behavioral and molecular responses to an LPS-induced immune challenge.
• To explore vortioxetine's impact on microglial activation and polarization in the hippocampus.

Main Methods:

• Mice were fed either a standard or vortioxetine-enriched diet for 28 days.
• An acute immune challenge was induced via peripheral lipopolysaccharide (LPS) injection.
• Behavioral tests (sickness, anhedonia, memory) and hippocampal molecular analyses (cytokines, microglial markers) were performed.

Main Results:

• Vortioxetine pretreatment did not alter LPS-induced sickness behavior or anhedonia.
• Vortioxetine prevented LPS-induced deficits in recognition memory.
• Vortioxetine modulated microglial M1/M2 polarization markers in an area-dependent manner and increased interleukin-4 expression.

Conclusions:

• Chronic vortioxetine administration specifically ameliorates LPS-induced memory impairment, independent of sickness behavior and anhedonia.
• Hippocampal microglia appear to be a cellular target for vortioxetine's cognitive effects.
• This study provides a model for investigating molecular mechanisms of cognitive impairment following immune challenges.