Chronological changes in the expression of phosphorylated tau and 5‑AMP‑activated protein kinase in the brain of senescence‑accelerated P8 mice.
Senescence-accelerated mouse prone 8 (SAMP8), a non‑transgenic 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‑ (2‑months‑old), middle‑ (5‑months‑old) and old‑aged (10‑months‑old) SAMP8. The levels of phosphorylated 5'‑AMP activated protein kinase at Thr172 (p‑AMPK) and phosphorylated glycogen synthase kinase 3β (p‑GSK3βS9) in the cortex of SAMP8 at 2 months were significantly higher than those in senescence‑accelerated 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 (p‑tauS396), but not with p‑tauS262. The level of p‑tauS262 was considerably higher in the cortex of middle‑aged SAMP8 when compared with that of SAMR1 and sustained in old‑aged SAMP8, but not in the young cortex. The levels of cortical sirtuin1 (Sirt1) and insulin receptor substrate 1 (IRS‑1) 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 p‑tau, p‑AMPK, Sirt1 and IRS‑1 relative to SAMR1 were different from those in the cortex. Taken together, the results suggested that regulation of tau phosphorylation via the AMPK‑GSK3β pathway concurrent with dysregulation of energy metabolism may precede the pathological tau hyperphosphorylation in the cortex of SAMP8, and that the regulation of AMPK‑GSK3β‑mediated tau phosphorylation may be dependent on phosphor‑epitope in tau or the region of brain.
Department of Pharmacology and Medicinal Toxicology Research Center, Inha University School of Medicine, Inha University, Incheon 22212, Republic of Korea.
Hak-Su
HS
Kim
Department of Pharmacology and Medicinal Toxicology Research Center, Inha University School of Medicine, Inha University, Incheon 22212, Republic of Korea.
Sohee
S
Moon
Department of Kinesiology, College of Arts and Sports, Inha University, Incheon 22212, Republic of Korea.
Sujin
S
Kim
Department of Kinesiology, College of Arts and Sports, Inha University, Incheon 22212, Republic of Korea.
Min-Jae
MJ
Lee
Department of Physical Education, College of Education, Seoul National University, Seoul 08826, Republic of Korea.
Min Hwa
MH
Suk
Department of Kinesiology, College of Arts and Sports, Inha University, Incheon 22212, Republic of Korea.
Dong-Ho
DH
Park
Department of Emergency Medicine, Inje University Ilsan Paik Hospital, Goyang, Gyeonggi 10380, Republic of Korea.
Dong Wun
DW
Shin
Department of Pharmacology and Medicinal Toxicology Research Center, Inha University School of Medicine, Inha University, Incheon 22212, Republic of Korea.
Chang-Shin
CS
Park
Department of Pharmacology and Medicinal Toxicology Research Center, Inha University School of Medicine, Inha University, Incheon 22212, Republic of Korea.
Ju-Hee
JH
Kang
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D004195:Disease Models, Animal; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D010766:Phosphorylation; D056564:Sirtuin 1 / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
D055504:Insulin Receptor Substrate Proteins; D016875:tau Proteins; D000071679:Glycogen Synthase Kinase 3 beta; D055372:AMP-Activated Protein Kinases; D056564:Sirtuin 1