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P1–408: Mitophagy pathway is induced by alginate oligosaccharide in PC12 cells exposed to oxidative stress
Author(s) -
Tusi Solaleh Khoramian,
Khodagholi Fariba,
Sanati Mohammad Hossein
Publication year - 2013
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.2013.05.636
Subject(s) - mitophagy , parkin , pink1 , mitochondrion , microbiology and biotechnology , oxidative stress , programmed cell death , oxidative phosphorylation , reactive oxygen species , apoptosis , chemistry , biology , biochemistry , autophagy , medicine , parkinson's disease , disease , pathology
Background: Interkeukin-6 (IL-6) is a pro-inflammatory cytokine found in cells, glia and neurons throughout the brain. Higher levels of IL-6 in older adults have been associated with physical and cognitive impairment (Jenny, French, Arnold, Strotmeyer, Cushman, Chaves et al., 2012), as well as increased dementia risk (Singh & Newman, 2010). The association between IL-6 levels and age-related brain changes is less clear. In the present study, we used longitudinal MRI data on brain structure to investigate the relation between IL-6 concentrations and the process of cortical thinning with age. Methods: MRI scans from the Baltimore Longitudinal Study of Aging were analyzed for 121 non-demented older subjects (M 1⁄4 73.3; SD 1⁄4 7.8; Range 1⁄4 56.1 94.1 yrs) who were repeatedly tested over an average period of 7.5 yrs. The Freesurfer longitudinal analysis processing stream was utilized for image processing of volumetric spoiled gradient recalled (SPGR)MR images, and IL-6 measures were based on serum ELISA assays (R&D System, Minneapolis, MN) with intra and interassay variations of 1.6% to 4.2% and 3.3% to 6.4% respectively. The minimum detectable dose (MDD) of IL-6 was less than 0.70 pg/ml. Statistical analysis was performed using a mixed effects model adapted for local analysis, with baseline age and sex as covariates. Results: Results showed that higher mean IL-6 concentrations were associated with accelerated annual rates of cortical thinning in the temporal poles bilaterally. Additional pronounced regions included the middle frontal gyrus, pars opercularis and lateral occipital gyrus within the left hemisphere, and lateral postcentral gyrus and inferior temporal gyrus within the right hemisphere (all maps thresholded to corresponding p values 0.0005-0.01). Conclusions: Our results indicate that persistently high levels of the inflammatory biomarker IL-6 are associated with an increased rate of age-related cortical thinning. These data build on previous findings that link IL-6 to chronic disease (Maggio, Guralnik, Longo & Ferrucci, 2006) and demonstrate one mechanism through which high levels of inflammation may have adverse effects on physical and cognitive function.