Poster abstracts

Poster number 89 submitted by Sarah Hopp

Blockade of L-VDCCs or RyRs during chronic neuroinflammation improves spatial memory, normalizes synaptic function, and reduces expression of inflammatory markers

Sarah C. Hopp (Neuroscience, The Ohio State University), Heather M. DAngelo, Sarah E. Royer (Neuroscience, The Ohio State University), Roxanne M. Kaercher (Psychology, The Ohio State University), Linda Adzovic (Psychology, The Ohio State University), Alexis M. Crockett (Neuroscience, The Ohio State University), Gary L. Wenk (Psychology, The Ohio State University)

Abstract:
Chronic neuroinflammation and calcium dysregulation are shared components of Alzheimer’s disease and other neurodegenerative processes. Prolonged neuroinflammation produces elevation of pro-inflammatory cytokines and reactive oxygen species which are capable of altering neuronal calcium homeostasis via L-type voltage dependent calcium channels (L-VDCCs) and ryanodine receptors (RyRs). Chronic neuroinflammation also leads to deficits in spatial memory, which may be related to calcium dysregulation. The studies herein use an in vivo model of chronic neuroinflammation: rats were treated with intraventricular infusion of lipopolysaccharide (LPS) for 28 days. Synaptosomes from LPS-infused rats have increased calcium uptake, which is decreased by pharmacological blockade of the L-VDCC either in vivo or ex vivo. LPS-infused rats had significant memory deficits in the Morris water maze; this deficit was ameliorated by treatment with an L-VDCC antagonist. Taken together, these data indicate that calcium dysregulation during chronic neuroinflammation is at least partially dependent on increases in L-VDCC function. However, blockade of the RyRs also slightly improves spatial memory of LPS-infused rats, demonstrating that other calcium channels are dysregulated during chronic neuroinflammation. Calcium-dependent immediate early gene expression was reduced to control levels in LPS-infused rats treated with L-VDCC or RyR antagonists, 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 calcium dysregulation via L-VDCCs and RyRs plays a crucial role in neuroinflammation-induced memory deficits.

Keywords: calcium, neuroinflammation, memory