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P2‐214: A NOVEL NEUROTOXIC ROLE OF THE APP INTRACELLULAR DOMAIN (AICD) AT THE MITOCHONDRIA, A DISTINCT MECHANISM FROM THAT OF Aβ
Author(s) -
Sandberg Alexandra A.,
Manning Evan,
Wilkins Heather M.,
Mazzarino Randall,
Minckley Taylor,
Qin Yan,
Patterson David,
Linseman Daniel
Publication year - 2019
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.2019.06.2621
Subject(s) - apoptosis , mitochondrion , transfection , microbiology and biotechnology , biology , intracellular , mitochondrial permeability transition pore , chemistry , amyloid beta , caspase , programmed cell death , cell culture , biochemistry , peptide , genetics
mitochondrial function, brain mitochondrial oxidative stress was increased, together with mitochondrial membrane depolarization. Both metformin and nec-1 equally increased %fEPSP slope of LTP, %preference of novel objects in both NOR and NOL tests, and decreased brain mitochondrial dysfunction. Treatment with metformin, but not nec-1, attenuated brain insulin resistance by decreasing %fEPSP slope of LTD (Figure 1). However, amyloid beta expression was not different among groups. Conclusions: Necroptosis inhibition effectively improved cognitive function via a restoration of synaptic plasticity and brain mitochondrial function in obese-insulin resistant rats, and this beneficial effect was independent to brain insulinresistant status.