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- W2084762017 abstract "The present study had focused on the behavioral phenotype and gene expression profile of molecules related to insulin receptor signaling in the hippocampus of 3 and 6 month-old APPswe/PS1dE9 (APP/PS1) transgenic mouse model of Alzheimer's disease (AD). Elevated levels of the insoluble Aβ (1–42) were detected in the brain extracts of the transgenic animals as early as 3 months of age, prior to the Aβ plaque formation (pre-plaque stage). By the early plaque stage (6 months) both the soluble and insoluble Aβ (1–40) and Aβ (1–42) peptides were detectable. We studied the expression of genes related to memory function (Arc, Fos), insulin signaling, including insulin receptor (Insr), Irs1 and Irs2, as well as genes involved in insulin growth factor pathways, such as Igf1, Igf2, Igfr and Igfbp2. We also examined the expression and protein levels of key molecules related to energy metabolism (PGC1-α, and AMPK) and mitochondrial functionality (OXPHOS, TFAM, NRF1 and NRF2). 6 month-old APP/PS1 mice demonstrated impaired cognitive ability, were glucose intolerant and showed a significant reduction in hippocampal Insr and Irs2 transcripts. Further observations also suggest alterations in key cellular energy sensors that regulate the activities of a number of metabolic enzymes through phosphorylation, such as a decrease in the Prkaa2 mRNA levels and in the pAMPK (Thr172)/Total APMK ratio. Moreover, mRNA and protein analysis reveals a significant downregulation of genes essential for mitochondrial replication and respiratory function, including PGC-1α in hippocampal extracts of APP/PS1 mice, compared to age-matched wild-type controls at 3 and 6 months of age. Overall, the findings of this study show early alterations in genes involved in insulin and energy metabolism pathways in an APP/PS1 model of AD. These changes affect the activity of key molecules like NRF1 and PGC-1α, which are involved in mitochondrial biogenesis. Our results reinforce the hypothesis that the impairments in both insulin signaling and energy metabolism precede the development of AD amyloidogenesis." @default.
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- W2084762017 date "2014-09-01" @default.
- W2084762017 modified "2023-10-16" @default.
- W2084762017 title "Early alterations in energy metabolism in the hippocampus of APPswe/PS1dE9 mouse model of Alzheimer's disease" @default.
- W2084762017 cites W1513394904 @default.
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- W2084762017 cites W1543788907 @default.
- W2084762017 cites W1589706085 @default.
- W2084762017 cites W1819313933 @default.
- W2084762017 cites W1867176171 @default.
- W2084762017 cites W1869566076 @default.
- W2084762017 cites W1966546615 @default.
- W2084762017 cites W1968553823 @default.
- W2084762017 cites W1975487612 @default.
- W2084762017 cites W1994061936 @default.
- W2084762017 cites W2002091021 @default.
- W2084762017 cites W2003093050 @default.
- W2084762017 cites W2005719973 @default.
- W2084762017 cites W2007265598 @default.
- W2084762017 cites W2011485908 @default.
- W2084762017 cites W2015265007 @default.
- W2084762017 cites W2017011351 @default.
- W2084762017 cites W2018494194 @default.
- W2084762017 cites W2026738811 @default.
- W2084762017 cites W2028660906 @default.
- W2084762017 cites W2028700140 @default.
- W2084762017 cites W2032095475 @default.
- W2084762017 cites W2034147064 @default.
- W2084762017 cites W2036183679 @default.
- W2084762017 cites W2038572225 @default.
- W2084762017 cites W2047977604 @default.
- W2084762017 cites W2053522766 @default.
- W2084762017 cites W2053549201 @default.
- W2084762017 cites W2055523148 @default.
- W2084762017 cites W2056880311 @default.
- W2084762017 cites W2057960819 @default.
- W2084762017 cites W2059005775 @default.
- W2084762017 cites W2059877494 @default.
- W2084762017 cites W2061814254 @default.
- W2084762017 cites W2062354481 @default.
- W2084762017 cites W2070740941 @default.
- W2084762017 cites W2071276938 @default.
- W2084762017 cites W2072595318 @default.
- W2084762017 cites W2076517751 @default.
- W2084762017 cites W2079206376 @default.
- W2084762017 cites W2080512251 @default.
- W2084762017 cites W2080709676 @default.
- W2084762017 cites W2080807247 @default.
- W2084762017 cites W2086336187 @default.
- W2084762017 cites W2088942395 @default.
- W2084762017 cites W2089616240 @default.
- W2084762017 cites W2096410114 @default.
- W2084762017 cites W2100978260 @default.
- W2084762017 cites W2103440561 @default.
- W2084762017 cites W2110789122 @default.
- W2084762017 cites W2112360486 @default.
- W2084762017 cites W2115439850 @default.
- W2084762017 cites W2123115740 @default.
- W2084762017 cites W2131710583 @default.
- W2084762017 cites W2132977458 @default.
- W2084762017 cites W2135026720 @default.
- W2084762017 cites W2135148756 @default.
- W2084762017 cites W2137204463 @default.
- W2084762017 cites W2137647318 @default.
- W2084762017 cites W2138521217 @default.
- W2084762017 cites W2140997352 @default.
- W2084762017 cites W2141282621 @default.
- W2084762017 cites W2144725252 @default.
- W2084762017 cites W2151252981 @default.
- W2084762017 cites W2155326661 @default.
- W2084762017 cites W2161597116 @default.
- W2084762017 cites W2163480486 @default.
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- W2084762017 cites W4210999100 @default.
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- W2084762017 doi "https://doi.org/10.1016/j.bbadis.2014.05.025" @default.
- W2084762017 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24887203" @default.
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