Peroxiredoxin II preserves cognitive function against age-linked hippocampal oxidative damage.
Reactive oxygen species (ROS), routinely produced in biological reactions, contribute to both normal aging and age-related decline in cognitive function. However, little is known regarding the involvement of specific antioxidants in the underlying mechanism(s). Here, we examined if peroxiredoxin II (Prx II) scavenges intracellular ROS that cause age-dependent mitochondrial decay in hippocampal CA1 pyramidal neurons and subsequent impairment of learning and memory. Age-dependent mitochondrial ROS generation and long-term potentiation (LTP) decline were more prominent in hippocampal neurons in Prx II(-/-) than in wild-type mice. Additionally, Prx II(-/-) mice failed to activate synaptic plasticity-related cellular signaling pathways involving CREB, CaMKII, and ERK, or to maintain functional integrity of their mitochondria. Dietary vitamin E alleviated Prx II deficiency-related deficits, including mitochondrial decay and CREB signaling, resulting in restoration of the abrupt cognitive decline in aged Prx II(-/-) mice. These results suggest that Prx II help maintain hippocampal synaptic plasticity against age-related oxidative damage.
Kim
Sun-Uk
SU
Aging Science Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea.
Jin
Mei-Hua
MH
Kim
Yoon Sik
YS
Lee
Sang-Hee
SH
Cho
Yee Sook
YS
Cho
Kyoung-Joo
KJ
Lee
Kyu-Sun
KS
Kim
Yang In
YI
Kim
Gyung Whan
GW
Kim
Jin-Man
JM
Lee
Tae-Hoon
TH
Lee
Young-Ho
YH
Shong
Minho
M
Kim
Hyung-Chun
HC
Chang
Kyu-Tae
KT
Yu
Dae-Yeul
DY
Lee
Dong-Seok
DS
D000284:Administration, Oral; D000375:Aging / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D001522:Behavior, Animal; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology*; D007859:Learning Disabilities / Q000178:diet therapy / Q000235:genetics; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008928:Mitochondria / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D054464:Peroxiredoxins / Q000172:deficiency / Q000378:metabolism*; D050050:Protein Carbonylation / Q000187:drug effects; D017382:Reactive Oxygen Species; D014810:Vitamin E / Q000008:administration & dosage
D000975:Antioxidants; D017382:Reactive Oxygen Species; D014810:Vitamin E; D008315:Malondialdehyde; D054464:Peroxiredoxins; D050882:CREB-Binding Protein; D017868:Cyclic AMP-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases