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P3‐072: Ascorbate deficiency interacts with icv‐STZ model of Alzheimer's in monkeys
Author(s) -
Lee KyoungMin,
Heo JaeHyeok
Publication year - 2012
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.2012.05.1291
Subject(s) - medicine , posterior cingulate , endocrinology , atrophy , saline , neuroprotection , precuneus , streptozotocin , neuroscience , chemistry , psychology , cortex (anatomy) , diabetes mellitus , cognition
Background: Oxidative stress is linked to the pathogenesis of neurodegeneration. 1) Beta-amyloid oligomers cause cognitive dysfunction and synaptotoxicity in AD. However, the relationship between oxidative stress, oligomer, and their localization during AD progression is not fully understood. Our group previously reported that mice deficient in cytoplasmic superoxide dismutase (CuZn-SOD, SOD1) have typical phenotypes of geriatric diseases, such as drusen in age-related macular degeneration, fatty liver, skin thinning and osteoporosis. 2) On the other hand, even though mitochondrial oxidative stress has been hitherto believed to be the main contributors to AD, the recent report revealed that mitochondrial SOD (MnSOD, SOD2) did not affect Ab oligomerization in vivo. 3) To evaluate the potential of cytoplasmic oxidative stress in AD, we generated an AD-model mouse lacking Sod 1 (h APP/Sod1 -/-), and analyzed it for AD-like pathology. Methods: Memory and behavioral abnormalities were estimated by Morris water maze and Y-maze. Ab oligomerization was tested on dot blotting and Western blotting. Senile plaque and neuroinflammation were evaluated using immunohistochemistry. The levels of tau, synaptophysin, each SOD were examined by Western blotting. hAPP processing was estimated on ELISA. Conclusions: These findings suggest that cytoplasmic oxidative stress could be involved in Ab aggregation (oligomerization), as well as production, and imply the role of intracellular Ab oligomerization. Activation of Sod1 may be a therapeutic strategy to delay AD progression. References: Murakami, K. et al., J. Amino Acids 2011, ID654207. Shimizu, T. et al., Geriatr. Gerontol. Int.2010, 10, S70-S79. Dumont, M. et al., FASEB J.2009, 23, 2459-2466. Murakami, K. et al., J. Biol. Chem. 2011, 286, 44557-44568.Murakami, K. et al., Biosci. Biotechnol. Biochem., in revision.