L-Type Ca²⁺ Channel Inhibition Rescues the LPS-Induced Neuroinflammatory Response and Impairments in Spatial Memory...

Area of Science:

• Neuroscience
• Pharmacology
• Immunology

Background:

• Microglial calcium (Ca2+) signaling regulates surveillance and activation states.
• L-type calcium channel blockers (CCBs) show potential in reducing neuroinflammation by modulating microglial activity.

Purpose of the Study:

• To investigate the effects of the L-type CCB felodipine on lipopolysaccharide (LPS)-induced neuroinflammatory responses.
• To explore felodipine's impact on microglial activation, signaling pathways, and cognitive function in vivo.

Main Methods:

• In vitro studies using BV2 microglial cells treated with LPS and felodipine.
• In vivo studies involving LPS-challenged C57BL/6 mice administered felodipine daily.
• Assessment of proinflammatory cytokine levels, TLR4/AKT/STAT3 signaling, gliosis, COX-2, IL-1β, spatial memory, and dendritic spine density.

Main Results:

• Felodipine significantly reduced LPS-evoked proinflammatory cytokines in BV2 cells via L-type calcium channel blockade.
• Felodipine inhibited TLR4/AKT/STAT3 signaling in LPS-stimulated BV2 microglial cells.
• In vivo, felodipine administration decreased LPS-induced gliosis, COX-2, IL-1β levels, spatial memory impairment, and microgliosis in mice.

Conclusions:

• Felodipine effectively suppresses LPS-mediated neuroinflammation and associated cognitive deficits.
• The L-type CCB felodipine demonstrates therapeutic potential for neuroinflammation and cognitive dysfunction.