The potent free radical scavenger α-lipoic acid improves memory in aged mice: Putative relationship to NMDA receptor deficits

doi:10.1016/0091-3057(93)90204-7

Pharmacology Biochemistry and Behavior

Volume 46, Issue 4, December 1993, Pages 799-805

https://doi.org/10.1016/0091-3057(93)90204-7 Get rights and content

Abstract

α-lipoic acid (α-LA) improved longer-term memory of aged female NMRI mice in the habituation in the open field test at a dose of 100 mg/kg body weight for 15 days. In a separate experiment, no such effect could be found for young mice. α-LA alleviated age-related NMDA receptor deficits (B_max) without changing muscarinic, benzodiazepine, and α₂-adrenergic receptor deficits in aged mice. The carbachol-stimulated accumulation of inositol monophosphates was not changed by the treatment with α-LA. These results give tentative support to the hypothesis that α-LA improves memory in aged mice, probably by a partial compensation of NMDA receptor deficits. Possible modes of action of α-LA based on its free radical scavenger properties are discussed in relation to the membrane hypothesis of aging.

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There are other nutrients able to influence the structure and function of mitochondria, either directly or through metabolites. Some of them act by alleviating oxidative stress (e.g., lipoic acid and hydroxytyrosol) [133,134], triggering phase II enzymes and increasing antioxidant defences (e.g., sulforaphane and tocopherol) [135,136], promoting mitochondrial remodelling (e.g., acetyl-L-carnitine) [137,138] and by protecting and stimulating mitochondrial enzymes (e.g., B vitamins and coenzyme Q) [133,137]. Lipoic acid is a cofactor for the pyruvate dehydrogenase and the α-ketoglutarate dehydrogenase complex.
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The potent free radical scavenger α-lipoic acid improves memory in aged mice: Putative relationship to NMDA receptor deficits

Abstract

Neurosci. Lett.

Brain Res.

Prostaglandins

Neurobiol. Aging

Neuropharmacology

Eur. J. Pharmacol.

J. Biol. Chem.

Neurosci. Let.

Biochim. Biophys. Acta

Mech. Ageing Dev.

Biochem. Pharmacol.

Brain Res.

Mech. Ageing Dev.

Neurobiol. Aging

Arch. Gerontol. Geriatr.

J. Theor. Biol.

Changes in the levels of inositol phosphates after agonist-dependent hydrolysis of membrane phosphoinositides

Biochem. J.

Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tert-butyl-alpha-phenylnitrone

Glutaminergic abnormalities in Alzheimer's disease and a rationale for clinical trials with L-glutamate

Clin. Neuropharmacol.

Enriching heredity. The impact of the environment on the anatomy of the brain