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Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid.
Proc Natl Acad Sci U S A. 2002 Feb 19; 99(4):2356-61.PN

Abstract

Accumulation of oxidative damage to mitochondria, protein, and nucleic acid in the brain may lead to neuronal and cognitive dysfunction. The effects on cognitive function, brain mitochondrial structure, and biomarkers of oxidative damage were studied after feeding old rats two mitochondrial metabolites, acetyl-l-carnitine (ALCAR) [0.5% or 0.2% (wt/vol) in drinking water], and/or R-alpha-lipoic acid (LA) [0.2% or 0.1% (wt/wt) in diet]. Spatial memory was assessed by using the Morris water maze; temporal memory was tested by using the peak procedure (a time-discrimination procedure). Dietary supplementation with ALCAR and/or LA improved memory, the combination being the most effective for two different tests of spatial memory (P < 0.05; P < 0.01) and for temporal memory (P < 0.05). Immunohistochemical analysis showed that oxidative damage to nucleic acids (8-hydroxyguanosine and 8-hydroxy-2'-deoxyguanosine) increased with age in the hippocampus, a region important for memory. Oxidative damage to nucleic acids occurred predominantly in RNA. Dietary administration of ALCAR and/or LA significantly reduced the extent of oxidized RNA, the combination being the most effective. Electron microscopic studies in the hippocampus showed that ALCAR and/or LA reversed age-associated mitochondrial structural decay. These results suggest that feeding ALCAR and LA to old rats improves performance on memory tasks by lowering oxidative damage and improving mitochondrial function.

Authors+Show Affiliations

Division of Biochemistry and Molecular Biology, University of California, Berkeley, CA 94720, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11854529

Citation

Liu, Jiankang, et al. "Memory Loss in Old Rats Is Associated With Brain Mitochondrial Decay and RNA/DNA Oxidation: Partial Reversal By Feeding acetyl-L-carnitine And/or R-alpha -lipoic Acid." Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 4, 2002, pp. 2356-61.
Liu J, Head E, Gharib AM, et al. Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid. Proc Natl Acad Sci U S A. 2002;99(4):2356-61.
Liu, J., Head, E., Gharib, A. M., Yuan, W., Ingersoll, R. T., Hagen, T. M., Cotman, C. W., & Ames, B. N. (2002). Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid. Proceedings of the National Academy of Sciences of the United States of America, 99(4), 2356-61.
Liu J, et al. Memory Loss in Old Rats Is Associated With Brain Mitochondrial Decay and RNA/DNA Oxidation: Partial Reversal By Feeding acetyl-L-carnitine And/or R-alpha -lipoic Acid. Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2356-61. PubMed PMID: 11854529.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid. AU - Liu,Jiankang, AU - Head,Elizabeth, AU - Gharib,Afshin M, AU - Yuan,Wenjun, AU - Ingersoll,Russell T, AU - Hagen,Tory M, AU - Cotman,Carl W, AU - Ames,Bruce N, PY - 2002/2/21/pubmed PY - 2002/3/26/medline PY - 2002/2/21/entrez SP - 2356 EP - 61 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 99 IS - 4 N2 - Accumulation of oxidative damage to mitochondria, protein, and nucleic acid in the brain may lead to neuronal and cognitive dysfunction. The effects on cognitive function, brain mitochondrial structure, and biomarkers of oxidative damage were studied after feeding old rats two mitochondrial metabolites, acetyl-l-carnitine (ALCAR) [0.5% or 0.2% (wt/vol) in drinking water], and/or R-alpha-lipoic acid (LA) [0.2% or 0.1% (wt/wt) in diet]. Spatial memory was assessed by using the Morris water maze; temporal memory was tested by using the peak procedure (a time-discrimination procedure). Dietary supplementation with ALCAR and/or LA improved memory, the combination being the most effective for two different tests of spatial memory (P < 0.05; P < 0.01) and for temporal memory (P < 0.05). Immunohistochemical analysis showed that oxidative damage to nucleic acids (8-hydroxyguanosine and 8-hydroxy-2'-deoxyguanosine) increased with age in the hippocampus, a region important for memory. Oxidative damage to nucleic acids occurred predominantly in RNA. Dietary administration of ALCAR and/or LA significantly reduced the extent of oxidized RNA, the combination being the most effective. Electron microscopic studies in the hippocampus showed that ALCAR and/or LA reversed age-associated mitochondrial structural decay. These results suggest that feeding ALCAR and LA to old rats improves performance on memory tasks by lowering oxidative damage and improving mitochondrial function. SN - 0027-8424 UR - https://www.unboundmedicine.com/medline/citation/11854529/Memory_loss_in_old_rats_is_associated_with_brain_mitochondrial_decay_and_RNA/DNA_oxidation:_partial_reversal_by_feeding_acetyl_L_carnitine_and/or_R_alpha__lipoic_acid_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&amp;pmid=11854529 DB - PRIME DP - Unbound Medicine ER -