title: β amyloid peptide plaques fail to alter evoked neuronal calcium signals in APP/PS1 Alzheimer's disease mice.
abstract: Alzheimer's disease (AD) is a multifactorial disorder of unknown etiology. Mechanistically, beta amyloid peptides (Aβ) and elevated Ca(2+) have been implicated as proximal and likely interactive features of the disease process. We tested the hypothesis that proximity to Aβ plaque might exacerbate activity-dependent neuronal Ca(2+) signaling in hippocampal pyramidal neurons from APPSWE/PS1M146V mice. Using combined approaches of whole cell patch clamp recording and 2-photon imaging of neuronal Ca(2+) signals with thioflavin-S plaque labeling in hippocampal slices, we found no correlation between thioflavin-S labeled Aβ plaque proximity and Ca(2+) responses triggered by ryanodine receptor (RyR) activation or action potentials in either dendrites or somata of AD mice, regardless of age. Baseline and RyR-stimulated spontaneous excitatory postsynaptic potentials also showed little difference in relation to Aβ plaque proximity. Consistent with previous studies, RyR-evoked Ca(2+) release in APPSWE/PS1M146V mice was greater than in nontransgenic controls. Within the soma, RyR-evoked Ca(2+) release was elevated in older APPSWE/PS1M146V mice compared with younger APPSWE/PS1M146V mice, but was still independent of plaque proximity. The results indicate that early Ca(2+) signaling disruptions can become yet more severe with age through mechanisms independent of Aβ plaques, suggesting that alternative pathogenic mechanisms might contribute to AD-associated dysfunction.
authors: Department of Neuroscience, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.
authors: Clark A
authors: CA
authors: Briggs
authors: Corinne
authors: C
authors: Schneider
authors: Jill C
authors: JC
authors: Richardson
authors: Grace E
authors: GE
authors: Stutzmann
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000009:adverse effects / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D020013:Calcium Signaling / Q000235:genetics*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000473:pathology; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D053764:Presenilin-1 / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1