PMID- 24388786
OWN - NLM
STAT- MEDLINE
DCOM- 20141125
LR  - 20220309
IS  - 1558-1497 (Electronic)
IS  - 0197-4580 (Print)
IS  - 0197-4580 (Linking)
VI  - 35
IP  - 6
DP  - 2014 Jun
TI  - Role of antioxidant enzymes in redox regulation of N-methyl-D-aspartate receptor 
      function and memory in middle-aged rats.
PG  - 1459-68
LID - S0197-4580(13)00627-1 [pii]
LID - 10.1016/j.neurobiolaging.2013.12.002 [doi]
AB  - Overexpression of superoxide dismutase 1 (SOD1) in the hippocampus results in 
      age-dependent impaired cognition and altered synaptic plasticity suggesting a 
      possible model for examining the role of oxidative stress in senescent 
      neurophysiology. However, it is unclear if SOD1 overexpression involves an 
      altered redox environment and a decrease in N-methyl-D-aspartate receptor (NMDAR) 
      synaptic function reported for aging animals. Viral vectors were used to express 
      SOD1 and green fluorescent protein (SOD1 + GFP), SOD1 and catalase (SOD1 + CAT), 
      or GFP alone in the hippocampus of middle-aged (17 months) male Fischer 344 rats. 
      We confirm that SOD1 + GFP and SOD1 + CAT reduced lipid peroxidation indicating 
      superoxide metabolites were primarily responsible for lipid peroxidation. SOD1 + 
      GFP impaired learning, decreased glutathione peroxidase activity, decreased 
      glutathione levels, decreased NMDAR-mediated synaptic responses, and impaired 
      long-term potentiation. Co-expression of SOD1 + CAT rescued the effects of SOD1 
      expression on learning, redox measures, and synaptic function suggesting the 
      effects were mediated by excess hydrogen peroxide. Application of the reducing 
      agent dithiolthreitol to hippocampal slices increased the NMDAR-mediated 
      component of the synaptic response in SOD1 + GFP animals relative to animals that 
      overexpress SOD1 + CAT indicating that the effect of antioxidant enzyme 
      expression on NMDAR function was because of a shift in the redox environment. The 
      results suggest that overexpression of neuronal SOD1 and CAT in middle age may 
      provide a model for examining the role of oxidative stress in senescent 
      physiology and the progression of age-related neurodegenerative diseases.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Lee, Wei-Hua
AU  - Lee WH
AD  - Department of Medical Genetics, University of Wisconsin, Madison, WI, USA.
FAU - Kumar, Ashok
AU  - Kumar A
AD  - Department of Neuroscience, McKnight Brain Institute, University of Florida, 
      Gainesville, FL, USA.
FAU - Rani, Asha
AU  - Rani A
AD  - Department of Neuroscience, McKnight Brain Institute, University of Florida, 
      Gainesville, FL, USA.
FAU - Foster, Thomas C
AU  - Foster TC
AD  - Department of Neuroscience, McKnight Brain Institute, University of Florida, 
      Gainesville, FL, USA. Electronic address: Foster1@ufl.edu.
LA  - eng
GR  - R01AG037984/AG/NIA NIH HHS/United States
GR  - P30 AG028740/AG/NIA NIH HHS/United States
GR  - R01 AG037984/AG/NIA NIH HHS/United States
GR  - R37 AG036800/AG/NIA NIH HHS/United States
GR  - R37AG036800/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20131209
PL  - United States
TA  - Neurobiol Aging
JT  - Neurobiology of aging
JID - 8100437
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - EC 1.11.1.6 (Catalase)
RN  - EC 1.15.1.1 (Sod1 protein, rat)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.15.1.1 (Superoxide Dismutase-1)
SB  - IM
MH  - Aging/*physiology
MH  - Animals
MH  - Catalase/physiology
MH  - Disease Progression
MH  - Hippocampus/enzymology
MH  - Male
MH  - Memory/*physiology
MH  - Neurodegenerative Diseases/*etiology
MH  - Neuronal Plasticity
MH  - Neurons/enzymology
MH  - Oxidation-Reduction
MH  - Oxidative Stress/physiology
MH  - Rats
MH  - Rats, Inbred F344
MH  - Receptors, N-Methyl-D-Aspartate/metabolism/*physiology
MH  - Superoxide Dismutase/*physiology
MH  - Superoxide Dismutase-1
MH  - Synapses/physiology
PMC - PMC3961498
MID - NIHMS547876
OTO - NOTNLM
OT  - Aging
OT  - Catalase
OT  - Glutathione peroxidase
OT  - Learning and memory
OT  - NMDAR
OT  - Superoxide dismutase
OT  - Synaptic plasticity
EDAT- 2014/01/07 06:00
MHDA- 2014/12/15 06:00
PMCR- 2015/06/01
CRDT- 2014/01/07 06:00
PHST- 2013/08/12 00:00 [received]
PHST- 2013/11/19 00:00 [revised]
PHST- 2013/12/04 00:00 [accepted]
PHST- 2014/01/07 06:00 [entrez]
PHST- 2014/01/07 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
PHST- 2015/06/01 00:00 [pmc-release]
AID - S0197-4580(13)00627-1 [pii]
AID - 10.1016/j.neurobiolaging.2013.12.002 [doi]
PST - ppublish
SO  - Neurobiol Aging. 2014 Jun;35(6):1459-68. doi: 
      10.1016/j.neurobiolaging.2013.12.002. Epub 2013 Dec 9.