Premium
P2‐270: Effect of the components of gamma‐secretase on activity and specificity
Author(s) -
Crump Christina J.,
Sisodia Sangram S.,
Li Yue-Ming
Publication year - 2010
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.2010.05.1320
Subject(s) - nicastrin , presenilin , gamma secretase , amyloid precursor protein , amyloid precursor protein secretase , alpha secretase , transmembrane protein , hek 293 cells , chemistry , microbiology and biotechnology , biochemistry , biology , alzheimer's disease , medicine , receptor , disease , pathology
Background: Central administration of streptozotocin causes cognitive impairment, alteration of glucose utilization with related metabolic pathway and oxidative-nitrosative stress which are prominent and well-established findings in incipient Alzheimer’s disease. Lycopene, a natural carotenoid has been reported to have beneficial effect in cognitive dysfunction. Present study was designed to evaluate the possible nitric oxide mechanism in protective effects of lycopene against the streptozotocin induced cognitive impairment and oxidative stress in rats. Methods: Streptozotocin (500mg/ 5ml) was administered intracerebroventricularly in rats. Animals were treated with lycopene (2.5 and 5 mg/kg, p.o.) daily for a period of 25 days beginning 4 days prior to streptozotocin injection. On the 14 and 21 day after streptozotocin administration, Morris water maze was performed for assessment of memory. Cytoplasmic and nuclear fractions of cerebral cortex and hippocampus were prepared for the quantification of oxidative stress parameters (lipidperoxidation, nitrite concentration, superoxide dismutase, catalase and reduced glutathione) mitochondrial enzymes (complex I,II,III & IV) activity, acetylcholinestrease activity and TNF-a level. Results: Lycopene treatment for 25days significantly improved memory retention, attenuated oxidative stress (reduced the elevated malondialdehyde, nitrite levels and restored SOD, catalase and acetylcholinesterase activity as well as the reduced glutathione levels), TNF-a and restored mitochondrial enzyme complex activities as compared to control (streptozotocin treated) animals. Further, L-arginine (50 mg/kg ip) pretreatment with sub effective dose of lycopene (2.5 mg/kg) significantly reversed the protective effect of lycopene. However, L-NAME (5 mg/kg ip) pretreatment with sub effective dose of lycopene (2.5 mg/kg) significantly potentiated the protective effect of lycopene which was significant as compared to their effect per se. Conclusions: The results of the present study suggest the nitric oxide mechanism might be involved in the protective effect of lycopene against streptozotocin-induced cognitive impairment and associated oxidative stress.