Modulation of learning, pain thresholds, and thermoregulation in the rat by preparations of free purified alpha-linolenic and linoleic acids: determination of the optimal omega 3-to-omega 6 ratio.

Yehuda, Shlomo; Carasso, R

doi:10.1073/pnas.90.21.10345

Cited by 155 publications

(85 citation statements)

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“…Salem and Niebylski [106] proposed that DHA or (22:6, n-3) controls the level of cholesterol as well as the composition and function of the neuronal membrane. We recently reviewed a number of studies that provided support for reducing neuronal membrane cholesterol by dietary supplementation of an n-3/n-6 compound in a ratio of 1:4 [125]. It is possible that such a ratio optimizes uptake of PUFA into the brain and promotes fatty acid incorporation into the neuronal membranes.…”

Section: Cholesterol and Fatty Acidsmentioning

confidence: 99%

“…the need for a proper ratio between the essential fatty acids. We experimentally tested our hypothesis that the ratio of n-3 and n-6 may be a key factor in modulating behavioral and neuropharmacological effects of PUFA, and we then attempted to identify the optimal ratio [125]. To avoid the variations that occur in the composition of fatty acids in commercially prepared oils, and to exclude the possible confounding effects of other fatty acid or lipid admixtures, we used highly purified alpha-linolenic and linoleic acids.…”

Section: Specific Fatty Acid and The Ratio Between Various Fatty Acidsmentioning

confidence: 99%

“…We tested a wide range of ratios of alpha-linolenic/linoleic acid (1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:5.5, 1:6 (v/v)) which were administered as dietary supplements. We found that a mixture of alpha-linolenic and linoleic acids with a ratio of 1:4 (which we referred to as SR-3) was the most effective in improving learning performance (as assessed by the Morris water maze), elevating pain threshold, improving sleep, and improving thermoregulation [125,128]. This compound was also able to correct learning deficits induced by the neurotoxins AF64A and 5,7-dihydroxytryptamine [127], and to provide protection from seizures induced by PTZ [126].…”

Section: Specific Fatty Acid and The Ratio Between Various Fatty Acidsmentioning

confidence: 99%

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The role of polyunsaturated fatty acids in restoring the aging neuronal membrane

Yehuda¹,

Rabinovitz²,

Carasso³

et al. 2002

Neurobiology of Aging

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In addition to a gradual loss of neurons in various brain regions, major biochemical changes in the brain affect the neuronal membrane that is the "site of action" for many essential functions including long-term potentiation (LTP), learning and memory, sleep, pain threshold, and thermoregulation. Normal physiological functioning includes the transmission of axonal information, regulation of membrane-bound enzymes, control of ionic channels and various receptors. All are highly dependent on membrane fluidity, where rigidity is increased during aging. The significantly higher level of cholesterol in aging neuronal membrane, the slow rate of cholesterol turnover, and the decreased level of total polyunsaturated fatty acids (PUFA) may result from poor passage rate via the blood-brain barrier, or from a decreased rate of incorporation into the membrane, or a decrease in the activities of delta-6 and delta-9 desaturase enzymes. The added oxidative stress, which leads to an increase of free radicals leading to a decrease in membrane fluidity, may respond to a restricted diet, and thereby overcome the damaging effects of the free radicals. A central focus of this review is that a specific ratio of n-3/n-6 PUFA can restore many of these age-related effects.

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Section: Cholesterol and Fatty Acidsmentioning

confidence: 99%

Section: Specific Fatty Acid and The Ratio Between Various Fatty Acidsmentioning

confidence: 99%

Section: Specific Fatty Acid and The Ratio Between Various Fatty Acidsmentioning

confidence: 99%

See 1 more Smart Citation

The role of polyunsaturated fatty acids in restoring the aging neuronal membrane

Yehuda¹,

Rabinovitz²,

Carasso³

et al. 2002

Neurobiology of Aging

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348

200

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“…Although the tests we used evaluate only a subset of cognitive abilities, our results suggest that, at the least, the KD does not worsen visuospatial learning and memory or exploratory behavior. Although we have not tested cognitive or behavioral effects of other AEDs in this kindling model, both clinical and experimental studies raise questions about such adverse sequelae in other models (35)(36)(37) showed that rats fed a diet enriched in essential fatty acids having a high w3/w6 ratio performed better on the Morris water maze than did rats fed a standard diet or a diet with a lower w3/06 ratio (38). The KD contains a mixture of saturated and polyunsaturated fatty acids, and the prospect that a KD could be designed to optimize cognitive function warrants further investigation.…”

Section: Previous Animal Studies Using the Kdmentioning

confidence: 99%

Ketogenic Diet: Effects on Expression of Kindled Seizures and Behavior in Adult Rats

et al. 1997

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Summary:Purpose: Despite use of the ketogenic diet (KD) for >75 years its effectiveness or mechanism of action has been examined in few animal studies. Using the kindling model of epilepsy, we tested the anticonvulsant effectiveness and behavioral consequences of an experimental KD in adult rats.Methods: Rats fully kindled from the amygdala were divided into KD-fed or standard rat diet-fed groups; diet treatment continued for 5 weeks. The KD approximated at 4:l ("classic") ketogenic diet and consisted (by weight) of 70% fat, 14% protein, no carbohydrate, and appropriate vitamins, minerals and fiber; 92% of energy provided was contributed by fat and 8% was contributed by protein. Afterdischarge threshold and duration (ADT, ADD) and stage 5 seizure threshold and duration (ST, SD) were assessed weekly for 5 weeks. During week 3, learning and memory were tested by the water maze and the behavioral response to a novel environment was assessed by the open field test.Results: Rats receiving the KD became ketonemic and had weight gains similar to those of control rats. As compared with rats receiving a standard diet, those fed the KD had an elevated ADT and ST for the first 2 weeks of treatment. The control and KD-fed groups did not differ with regard to ADD or SD at any time during the study, and both groups performed similarly in the water maze and open field test.Conclusions: In the kindling model, the KD afforded transient protection against the focal generation of kindled seizures but not seizure spread. Rats that received the KD did not perform differently from control-fed rats on spatial learning or exploratory behavior tasks. Our results provide a promising model for study of the anticonvulsant mechanisms of ketosis. Key Words: Ketogenic diet-Kindling-Seizure-Afterdischarge threshold-Water maze.The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that has been used for treatment of refi-actory seizures for >75 years (1). Nevertheless, information on the optimal formulation of the diet, the seizure types in which it might be most effective, and the characteristics of patients who might benefit from its use is limited (2,3). Despite extensive clinical use of the KD, surprisingly few investigators have attempted to determine how and even whether the KD works (3,4). Furthermore, although anecdotal reports cite improved cognition and alertness in patients receiving the KD (5,6), this claim has not been evaluated in any well-controlled clinical or experimental studies.The KD was used widely before antiepileptic drugs (AEDs) became available, but since the advent of modern pharmacological therapy, the KD has largely been paring and maintaining a patient on the KD is often a daunting challenge for both family and physician. Recently, however, there has been a resurgence of interest in the KD (2,7), which has given impetus to efforts designed to verify experimentally the effectiveness and optimal indications of this increasingly popular but unconventional therapy.Animal models offer several advantages for investi...

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“…Ainsi, un régime supplémenté en AGPI n-3 semble améliorer les performances dans le test discrimination visuelle [11] et dans le test de la piscine de Morris [13] déjà évoqués. Au vu de l'ensemble des résultats obtenus en cas de déficience et en cas de surcharge, on peut proposer l'existence d'une valeur « idéale » d'apport en AGPI n-3 ou de rapport AGPI n-6/n-3 pour des capacités cognitives optimales [20].…”

Section: Articleunclassified

Acides gras poly-insaturés et fonctions cognitives

Chalon

2001

OCL

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Résumé : L'influence des AGPI sur les fonctions cognitives peut être abordé par le biais de tests comportementaux réalisés chez des animaux soumis à des régimes alimentaires à teneurs variables et contrôlées en AGPI n-6 et n-3. Plusieurs études montrent que la déficience en AGPI n-3 induit une diminution des capacités d'apprentissage tandis que la supplémentation en DHA améliore ces fonctions. Cependant, il est difficile de distinguer entre des effets directs sur l'apprentissage et/ou sur des paramètres de performances tels que les fonctions visuelles, la motivation, l'attention, la réactivité aux stimuli. Les mécanismes impliqués dans ces effets sont encore mal élucidés. Les AGPI peuvent agir sur les fonctions cognitives via des effets sur les propriétés physiques des membranes cérébrales, entraînant des conséquences sur les protéines incluses dans ces membranes telles que les récepteurs et les transporteurs. Les AGPI peuvent aussi agir directement sur le génome. Par ailleurs, les effets des AGPI peuvent passer par les systèmes de signalisation cellulaire, puisqu'ils sont des précurseurs des eicosanoïdes. De plus, on dispose de plus en plus d'arguments en faveur de l'influence des AGPI sur les processus de neurotransmission, notamment dopaminergique, sérotoninergique et cholinergique. Chez l'homme, il est plus difficile d'évaluer l'influence des AGPI sur les fonctions cognitives que chez l'animal. Cependant, des données concernant l'évaluation mentale au cours de la période de développement et les relations entre le statut en AGPI et les désordres neuropsychiatriques sont en faveur d'un réel impact des AGPI sur le fonctionnement cérébral. Ce champ d'investigation illustre parfaitement le rôle potentiel des facteurs environnementaux sur la santé mentale.Mots-clés : comportement, DHA, neurotransmission monoaminergique. Summary :The role of essential fatty acids in cerebral function can be approached using animal models receiving controlled dietary supply of n-3 and n-6 PUFAs. Several findings showed that a n-3 PUFA deficiency reduced the learning abilities whereas DHA supply improved these functions. However, it is difficult to distinguish between direct effects on learning and effects on performance factors such as visual competence, motivation, attention, or sensory threshold. The mechanisms involved in these effects are still partly unknown. PUFAs can act on cognitive functions through effects on the physical properties of cerebral membranes, with possible consequences on anchored proteins (receptors, transporters). They can also directly act on gene functions. In addition, effects of PUFAs can be mediated through a role on cell signalling, as they are eicosanoid precursors. Globally, more and more evidences are in agreement with influence of the PUFA status on neurotransmission processes, especiallyArticle disponible sur le site http://www.ocl-journal.org ou http://dx

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Modulation of learning, pain thresholds, and thermoregulation in the rat by preparations of free purified alpha-linolenic and linoleic acids: determination of the optimal omega 3-to-omega 6 ratio.

Abstract: Ingested polyunsaturated fatty acids are pos-

Cited by 155 publications

References 42 publications

The role of polyunsaturated fatty acids in restoring the aging neuronal membrane

The role of polyunsaturated fatty acids in restoring the aging neuronal membrane

Ketogenic Diet: Effects on Expression of Kindled Seizures and Behavior in Adult Rats

Acides gras poly-insaturés et fonctions cognitives

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