Cited by 459Alzheimer's disease research and treatmentsAntioxidants, Aging, Portulaca oleraceaAntioxidant Activity and Oxidative Stress

The antioxidants α‐lipoic acid and N ‐acetylcysteine reverse memory impairment and brain oxidative stress in aged SAMP8 mice

Farr, Susan A., Poon, H. Fai, Dogrukol‐Ak, Dilek, Drake, Jeniffer, Banks, William A., Eyerman, Edward, Butterfield, D. Allan, Morley, John E.·2003·Journal of Neurochemistry

Abstract

Oxidative stress may play a crucial role in age-related neurodegenerative disorders. Here, we examined the ability of two antioxidants, alpha-lipoic acid (LA) and N-acetylcysteine (NAC), to reverse the cognitive deficits found in the SAMP8 mouse. By 12 months of age, this strain develops elevated levels of Abeta and severe deficits in learning and memory. We found that 12-month-old SAMP8 mice, in comparison with 4-month-old mice, had increased levels of protein carbonyls (an index of protein oxidation), increased TBARS (an index of lipid peroxidation) and a decrease in the weakly immobilized/strongly immobilized (W/S) ratio of the protein-specific spin label MAL-6 (an index of oxidation-induced conformational changes in synaptosomal membrane proteins). Chronic administration of either LA or NAC improved cognition of 12-month-old SAMP8 mice in both the T-maze footshock avoidance paradigm and the lever press appetitive task without inducing non-specific effects on motor activity, motivation to avoid shock, or body weight. These effects probably occurred directly within the brain, as NAC crossed the blood-brain barrier and accumulated in the brain. Furthermore, treatment of 12-month-old SAMP8 mice with LA reversed all three indexes of oxidative stress. These results support the hypothesis that oxidative stress can lead to cognitive dysfunction and provide evidence for a therapeutic role for antioxidants.

Integrity signals

Registry

Crossref · 10.1046/j.1471-4159.2003.01580.x

Cites

91 of 91 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Alpha-lipoic acid is a cofactor for pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase, which are key components in glucose metabolism; when given to dogs and rodents, it decreases oxidative damage in the brain and improves cognition.

    “Alpha-lipoic acid is a cofactor for pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase, which are key components in glucose metabolism; when given to dogs and rodents, it decreases oxidative damage in the brain and improves cognition [149,150].”
  • NAC enters the brain at a very modest rate due to low bioavailability and membrane permeability.

    “However, the beneficial effect of NAC has to be taken with caution since the current data is based on only a few studies showing relatively moderate clinical improvement in chronic schizophrenia patients, probably due to the low bioavailability and membrane permeability of NAC which enters the brain at a very modest rate (Farr et al., 2003).”
  • Sulforaphane has shown some promise in a preliminary open-label trial for schizophrenia.

    “one, sulforaphane, has shown some promise in a preliminary open-label trial for SZ 106”

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Farr, S. A., Poon, H. F., Dogrukol‐Ak, D., Drake, J., Banks, W. A., Eyerman, E., Butterfield, D. A., & Morley, J. E.
Affiliations
  • St. Louis VA Medical Center (US)
  • University of Kentucky (US)
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2003-02-18
Volume
84
Issue
5
Pages
1173-1183
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
OpenAlex
W2132870100
Cited by
459
References
91
Citations by year
2026: 5 · 2025: 10 · 2024: 16 · 2023: 15 · 2022: 17 · 2021: 19 · 2020: 25 · 2019: 17 · 2018: 18 · 2017: 24 · 2016: 14 · 2015: 15 · 2014: 27 · 2013: 24 · 2012: 23
FWCI
13.61
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Veterans Affairs
  • National Institute on Alcohol Abuse and Alcoholism (R01AA12743, R01AA012743)
  • National Institute of Neurological Disorders and Stroke (R0-1 NS41863, R01NS041863)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Antioxidants, Aging, Portulaca oleracea
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Keywords
alpha-lipoic acid, N-acetylcysteine, antioxidants, oxidative stress, memory impairment, SAMP8 mice, aging, cognitive impairment, amyloid-beta, protein carbonyls, lipid peroxidation, blood-brain barrier, neurodegeneration
MeSH terms
Acetylcysteine, Age Factors, Animals, Antioxidants, Appetitive Behavior, Behavior, Animal, Blood-Brain Barrier, Brain, Cognition, Disease Models, Animal, Thioctic Acid, Male, Memory Disorders, Mice, Inbred Strains, Mice, Neurologic Mutants, Specific Pathogen-Free Organisms, Amyloid beta-Peptides, Treatment Outcome, Oxidative Stress, Maze Learning, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review