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P2‐042: Structural proteins in focus: New insights in the hippocampal progression of Alzheimer's disease
Author(s) -
Schroetter Andreas
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.2015.06.578
Subject(s) - hippocampal formation , laser capture microdissection , fascia dentata , neuroscience , hippocampus , biology , human brain , alzheimer's disease , dementia , atrophy , pathology , disease , medicine , dentate gyrus , biochemistry , genetics , gene expression , gene
gel electrophoresis (2D-DIGE) coupled with mass spectrometry was performed to screen the potential key molecules involved in spatial memory impairment in triple transgenic (3XTg-AD) mice harboring PS1M146V, APPSwe, and tau p301L transgenes. Results: Compared with the age-matched controls, a total of 23 differentially expressed proteins were identified in hippocampus of the 3XTg-AD mice at 9 month-old when the mice displayed significant spatial memory impairment. These differentially expressed proteins can be categorized into several functional classifications including the proteins involved in synaptic/memory-, energy metabolism-, intracellular transport-, cell cycle-, cellular defense and structure-related and stress response proteins. To further verify the target proteins that may underlie the memory deficits, we treated the 6 month-old 3XTg-AD mice for 3 months with coenzyme Q10 (CoQ10) (800 mg/kg body weight/day), a powerful endogenous antioxidant that has shown memory protection in other AD mouse models. We found that administration of CoQ10 changed the expression levels of 8 proteins in hippocampus of 3XTg-AD mice with a simultaneous improvement of the spatial memory. Interestingly, only complexin 2 and tubulin alpha-1B, two recognized memory-associated proteins, were modulated (i.e., the levels were reduced in 3XTg-AD mice and CoQ10 restored the levels) by CoQ10 among these 8 proteins. Therefore, we further confirmed the reduction of these two molecules in 3XTg-ADmice and the restoration by CoQ10 byWesternblotting. Conclusions: Taken together, our data suggest that complexin 2 and tubulin alpha-1B may underlie the molecular basis of memory loss in AD.