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P3‐409: DIPEPTIDYL PEPTIDASE‐4 INHIBITION BY PTEROCARPUS MARSUPIUM AND EUGENIA JAMBOLANA AMELIORATES STREPTOZOTOCIN‐INDUCED ALZHEIMER'S DISEASE
Author(s) -
Kosaraju Jayasankar,
Chinni Santhivardhan,
Khatwal Rizwan Basha,
Dubala Anil,
Muthureddy Nataraj Satish Kumar,
Basavan Duraiswamy
Publication year - 2014
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.2014.05.1504
Subject(s) - neuroprotection , neuroinflammation , streptozotocin , pharmacology , amyloid beta , dipeptidyl peptidase 4 inhibitor , medicine , dipeptidyl peptidase 4 , dipeptidyl peptidase , hippocampus , diabetes mellitus , dementia , endocrinology , type 2 diabetes , chemistry , biochemistry , disease , enzyme
Background:The human brain is enriched in omega series unsaturated fatty acids (FAs) whose deficiencies have been linked to a variety of neurological disorders including AD. Intriguingly, AD patients have reduced levels of €I&-3 and€I&-6/9 FAs compared with age-matched non-demented controls. More importantly, their levels were shown to correlate with severity of mild cognitive impairment (MCI) and dementia. These observations have prompted us to investigate whether dietary supplementation of the omega series FAs may restore their normal levels and thus improve learning and memory in the TgCRND8 AD mouse model. Methods: TgCRND8 mice and their NonTg littermates received €I&-3 or €I&-6/9 FAs (75mg/Kg/day) supplementation for 4 months starting at 2 months of age. Mice received vehicle were used as “untreated” controls. The glycerophosphocholine (PC) lipidomewas profiled in the hippocampus, temporal cortex, and plasma in these mice following assessment of learning and memory in the Morris Water Maze (MWM). PCs were extracted using a modified Bligh & Dyer method and profiling was performed by LC-ESI-MS. Results: TgCRND8 mice displayed learning and memory impairment compared to NonTg littermates. We further showed that the TgCRND8 mice used a less effective search strategy than NonTg littermates in theMWM test. Therewere 24 PC species whose abundance was significantly altered in the TgCRND8 mice. Significant correlations between the abundance of 13 species in either the hippocampus or temporal cortex were detected that could be predicted by associated changes in circulating lipidome. While supplementation with €I&-3 FA did not improve learning and memory of the transgenic mice, supplementation with€I&-6/-9 FAs significantly improved their performance in the MWM test due at least in part to adoption of a more effective searching strategy. Overall, dietary supplementation of FAs appeared to have more profound effects on plasma PC lipidome than genotype did as revealed by cluster analysis. Importantly, the abundance of six plasma PC species was significantly correlated with individual learning and memory. Conclusions: These data provide proof of principle that the central and circulating lipidome can be modulated to improve learning and memory.