Age-dependent modulation of hippocampal long-term potentiation by antioxidant enzymes.
Oxidative stress has long been associated with normal aging and age-related neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). However, it is now evident that reactive oxygen species (ROS) such as superoxide (O(2-*)) and hydrogen peroxide (H(2)O(2)) also play pivotal roles in normal cell signaling. The focus of the present study was to examine the effects of the antioxidant enzymes CuZnSOD (SOD1) and catalase, which produce and remove H(2)O(2), respectively, on long-term potentiation (LTP) forms of synaptic plasticity during aging. Consistent wth previous studies, LTP, when induced in vitro in CA1 of the hippocampus with a high-frequency stimulation protocol, is significantly reduced in slices from older mice (22-26 months) relative to younger mice (2-4 months). Neither knockout of the endogenous catalase gene (Cat KO) nor acute enzymatic treatment with SOD1 altered LTP in slices from adult mice. Conversely, enzymatic applications of SOD1 inhibited LTP in slices from older mice. A much different set of results emerges with exogenous applications of catalase to hippocampal slices. Catalase significantly inhibited LTP in slices from adult mice but reversed age-related LTP deficits in slices from older mice. Measurements of H(2)O(2) showed that exogenous treatments with catalase lowered H(2)O(2) in synapse-enriched synaptoneurosome (SN) fractions prepared from adult mice. Notably, SNs from both Cat KO and old mice were deficient in removing extracellular challenges of H(2)O(2). Overall, the results suggest that dynamic alterations in extracellular H(2)O(2) metabolism affect synaptic plasticity in the hippocampus during aging.
Watson
J B
JB
Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA. jwatson@mednet.ucla.edu
Arnold
M M
MM
Ho
Y-S
YS
O'Dell
T J
TJ
D000375:Aging / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002374:Catalase / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D013482:Superoxide Dismutase / Q000494:pharmacology / Q000502:physiology*; D000072105:Superoxide Dismutase-1; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics
D006861:Hydrogen Peroxide; D002374:Catalase; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1