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P1‐042: Activation of glycogen synthase kinase‐3 mediates the olfactory deficit‐induced hippocampal impairments
Author(s) -
Zhu Ling-Qiang
Publication year - 2015
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.2015.06.238
Subject(s) - neuroscience , synaptophysin , hippocampus , synaptic plasticity , olfactory memory , synapsin i , biology , long term potentiation , dendritic spine , olfactory bulb , kinase , chemistry , hippocampal formation , microbiology and biotechnology , biochemistry , central nervous system , vesicle , receptor , immunohistochemistry , membrane , synaptic vesicle , immunology
AD. One of the triggering factors for oxidative stress is “iron”. Free iron leads to the formation of reactive oxygen species that are neurotoxic. Iron has been found co-localized with amyloid beta (Ab) plaques and hyper phosphorylated tau (HP-tau) – hallmarks of AD. We propose an iron hypothesis for AD that may explain the affinity of iron to different proteins. We hypothesize that production of these proteins are attempts by neurons to ameliorate oxidative damage by binding iron. However, we do not know the pathophysiological mechanism behind this. We propose to study this mechanism using a murine model, triggering controlled oxidative stress to increase iron and treatments to rescue that insult. We will analyze the co-localization of iron with Ab and HP-tau using Nuclear magnetic resonance (NMR), gel electrophoresis, western blot and MRI. Methods:We have acquired the NMR of different iron bound proteins to determine relaxation values in terms of T1, T2 and T2*. These values will be used to inform MRI scans so as to develop a technique to differentiate ironbound Ab and HP-tau. In parallel, T2* and 3DCones images of post-mortem brain were also obtained in an attempt to localize pathological depositions of protein. Results:Wehave determined T1, T2 and T2* values of iron-bound proteins and appropriate controls. These values of pure and ex vivo samples of ironbound AD proteins from NMR will inform our search for these proteins using MRI. 3D Cones images of post mortem brain showed the localization of iron in the hippocampus. We expect the gel electrophoresis and western blot results to show the expression of different proteins according to the treatment or stages of the sample. Conclusions: Iron bound pro-