Calcium dysregulation via L-type voltage-dependent calcium channels and ryanodine receptors underlies memory deficits and synaptic dysfunction during chronic neuroinflammation

Sarah C. Hopp, Heather M. D'Angelo, Sarah E. Royer, Roxanne M. Kaercher, Alexis M. Crockett, Linda Adzovic, Gary L. Wenk

Research output: Contribution to journalArticle

12 Scopus citations


Background: Chronic neuroinflammation and calcium (Ca+2) dysregulation are both components of Alzheimer's disease. Prolonged neuroinflammation produces elevation of pro-inflammatory cytokines and reactive oxygen species which can alter neuronal Ca+2 homeostasis via L-type voltage-dependent Ca+2 channels (L-VDCCs) and ryanodine receptors (RyRs). Chronic neuroinflammation also leads to deficits in spatial memory, which may be related to Ca+2 dysregulation. Methods: The studies herein use an in vivo model of chronic neuroinflammation: rats were infused intraventricularly with a continuous small dose of lipopolysaccharide (LPS) or artificial cerebrospinal fluid (aCSF) for 28days. The rats were treated with the L-VDCC antagonist nimodipine or the RyR antagonist dantrolene. Results: LPS-infused rats had significant memory deficits in the Morris water maze, and this deficit was ameliorated by treatment with nimodipine. Synaptosomes from LPS-infused rats had increased Ca+2 uptake, which was reduced by a blockade of L-VDCCs either in vivo or ex vivo. Conclusions: Taken together, these data indicate that Ca+2 dysregulation during chronic neuroinflammation is partially dependent on increases in L-VDCC function. However, blockade of the RyRs also slightly improved spatial memory of the LPS-infused rats, demonstrating that other Ca+2 channels are dysregulated during chronic neuroinflammation. Ca+2-dependent immediate early gene expression was reduced in LPS-infused rats treated with dantrolene or nimodipine, indicating normalized synaptic function that may underlie improvements in spatial memory. Pro-inflammatory markers are also reduced in LPS-infused rats treated with either drug. Overall, these data suggest that Ca+2 dysregulation via L-VDCCs and RyRs play a crucial role in memory deficits resulting from chronic neuroinflammation.

Original languageEnglish (US)
Article number56
JournalJournal of Neuroinflammation
Issue number1
StatePublished - Mar 25 2015
Externally publishedYes



  • Calcium
  • L-type voltage-dependent calcium channels
  • Neuroinflammation
  • Ryanodine receptors
  • Spatial memory

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this