Enhanced Ryanodine Receptor Recruitment Contributes to Ca2+Disruptions in Young, Adult, and Aged Alzheimer's Disease Mice

• DOI: 10.1523/jneurosci.0739-06.2006
• Publication Date: 2006-05-10T16:51:05Z
• Authors: Grace E. Stutzmann; Ian Smith; Antonella Caccamo; Salvatore Oddo; Frank M. LaFerla; Ian Parker
• Keywords: Calcium Signaling

Neuronal Ca 2+ signaling through inositol triphosphate receptors (IP 3 R) and ryanodine (RyRs) must be tightly regulated to maintain cell viability, both acutely over a lifetime. Exaggerated intracellular levels have been associated with expression of Alzheimer's disease (AD) mutations in young mice, but little is known dysregulations during normal pathological aging processes. Here, we used electrophysiological recordings two-photon imaging study nontransgenic (NonTg) several AD mouse models (PS1 KI , 3xTg-AD, APP Swe Tau P301L ) at (6 week), adult months), old (18 months) ages. At all ages, the PS1 3xTg-AD mice displayed exaggerated endoplasmic reticulum (ER) signals relative NonTg mice. The mutation was predominant “calciopathic” factor, because responses were similar not different from controls. In addition, uncovered powerful interactions differences between IP R- RyR-mediated components RyR contributed modestly -evoked whereas resulted primarily enhanced RyR-Ca release increased across Moreover, membrane hyperpolarizations even greater than expected signals, suggesting coupling efficiency cytosolic [Ca ] K + channel regulation. We conclude that lifelong ER disruptions are related modulation represent discrete “calciumopathy,” merely an acceleration aging.