Senescence-accelerated mouse prone 8 (SAMP8), a nontransgenic animal model used for researching sporadic Alzheimer's disease (AD), presents AD pathologies and overall dysregulation in brain energy metabolism, which is one of the early pathogenic characteristics of AD. In the present
study, the authors examined chronological changes in the expression patterns of phosphorylated tau and of proteins related to energy metabolism to evaluate the association of tau phosphorylation and metabolism, using young (2monthsold), middle (5monthsold) and oldaged (10monthsold) SAMP8.
The levels of phosphorylated 5'AMP activated protein kinase at Thr172 (pAMPK) and phosphorylated glycogen synthase kinase 3β (pGSK3βS9) in the cortex of SAMP8 at 2 months were significantly higher than those in senescenceaccelerated mouse resistant 1 (SAMR1). The differences
were not detected at 5 and 10 months of age, which were concurrent with the changes in levels of phosphorylated tau at Ser396 (ptauS396), but not with ptauS262. The level of ptauS262 was considerably higher in the cortex of middleaged SAMP8 when compared with that of SAMR1 and sustained
in oldaged SAMP8, but not in the young cortex. The levels of cortical sirtuin1 (Sirt1) and insulin receptor substrate 1 (IRS1) expression of young SAMP8 were significantly lower, when compared with those in SAMR1. However, in the hippocampus of SAMP8, the patterns of chronological changes
and levels of ptau, pAMPK, Sirt1 and IRS1 relative to SAMR1 were different from those in the cortex. Taken together, the results suggested that regulation of tau phosphorylation via the AMPKGSK3β pathway concurrent with dysregulation of energy metabolism may precede the pathological tau
hyperphosphorylation in the cortex of SAMP8, and that the regulation of AMPKGSK3βmediated tau phosphorylation may be dependent on phosphorepitope in tau or the region of brain.
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Document Type: Research Article
Department of Pharmacology and Medicinal Toxicology Research Center, Inha University School of Medicine, Inha University, Incheon 22212, Republic of Korea
Department of Kinesiology, College of Arts and Sports, Inha University, Incheon 22212, Republic of Korea
Department of Physical Education, College of Education, Seoul National University, Seoul 08826, Republic of Korea
Department of Emergency Medicine, Inje University Ilsan Paik Hospital, Goyang, Gyeonggi 10380, Republic of Korea
Publication date: January 1, 2017
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Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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