Premium
P2‐195: Organelle‐targeted Ca2+ probes help to visualize store Ca2+ handling by wild‐type and mutant presenilin‐2
Author(s) -
Zampese Enrico,
Brunello Lucia,
Lissandron Valentina,
Pozzan Tullio,
Pizzo Paola,
Fasolato Cristina
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.04.507
Subject(s) - serca , mutant , endogeny , golgi apparatus , organelle , microbiology and biotechnology , wild type , presenilin , endoplasmic reticulum , biology , mitochondrion , chemistry , atpase , biochemistry , enzyme , medicine , gene , disease , alzheimer's disease
well understood. In cultured murine hippocampal neurons expressing human presenilin1 (PS1) with the A246E mutation we demonstrated reduced AMPAand NMDA-receptor mediated synaptic currents as well as a decrease in the frequency of spontaneous miniature currents. This depression of synaptic transmission was ascribed to a physical reduction in the number of synapses in these neurons. Methods: To confirm these findings in vivo we performed two photon microscopy of sparse fluorescent labelled neurons in the somatosensory cortex of transgenic mice overexpressing either the A246E mutated or the human wildtype PS1. Results: This technique enabled us not only to determine and compare the density of postsynaptic protrusions of the cortical excitatory neurons, namely the dendritic spines, but also allowed a morphological classification. Furthermore with chronic in vivo imaging of the same dendritic elements we functionally characterized these spines depending on the A246E mutation. Conclusions: Together these results define the influence of mutated PS1 on the structural plasticity of cortical synapses that will help to elucidate the role of PS1 in synaptic dysfunction seen in Alzheimer disease.