L-Type Ca 2+ Channel Inhibition Rescues the LPS-Induced Neuroinflammatory Response and Impairments in Spatial Memory and Dendritic Spine Formation.
Jieun KimSeong Gak JeonHa-Ram JeongHyunHee ParkJae-Ick KimHyang-Sook HoePublished in: International journal of molecular sciences (2022)
Ca 2+ signaling is implicated in the transition between microglial surveillance and activation. Several L-type Ca 2+ channel blockers (CCBs) have been shown to ameliorate neuroinflammation by modulating microglial activity. In this study, we examined the effects of the L-type CCB felodipine on LPS-mediated proinflammatory responses. We found that felodipine treatment significantly diminished LPS-evoked proinflammatory cytokine levels in BV2 microglial cells in an L-type Ca 2+ channel-dependent manner. In addition, felodipine leads to the inhibition of TLR4/AKT/STAT3 signaling in BV2 microglial cells. We further examined the effects of felodipine on LPS-stimulated neuroinflammation in vivo and found that daily administration (3 or 7 days, i.p.) significantly reduced LPS-mediated gliosis and COX-2 and IL-1β levels in C57BL/6 (wild-type) mice. Moreover, felodipine administration significantly reduced chronic neuroinflammation-induced spatial memory impairment, dendritic spine number, and microgliosis in C57BL/6 mice. Taken together, our results suggest that the L-type CCB felodipine could be repurposed for the treatment of neuroinflammation/cognitive function-associated diseases.
Keyphrases
- lps induced
- inflammatory response
- lipopolysaccharide induced
- toll like receptor
- wild type
- induced apoptosis
- working memory
- signaling pathway
- public health
- type diabetes
- cell cycle arrest
- traumatic brain injury
- protein kinase
- adipose tissue
- cognitive impairment
- diabetic rats
- anti inflammatory
- spinal cord injury
- cell death
- high glucose
- pi k akt
- smoking cessation