The chronic administration of docosahexaenoic acid reduces the spatial cognitive deficit following transient forebrain ischemia in rats

Okada, Mitsuko; Amamoto, Toshiaki; Tomonaga, Masamichi; Kawachi, Asuka; Yazawa, Kazuyoshi; Mine, Kazunori; Fujiwara, Michihiro

doi:10.1016/0306-4522(95)00427-0

Cited by 99 publications

(57 citation statements)

References 34 publications

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“…In addition, it has been indicated that low levels of DHA in brain are associated with neurodegenerative diseases, such as generalized peroxisomal disorders (12) and Alzheimer's disease (13). Furthermore, DHA supplementation has been shown to alleviate symptoms in some patients with peroxisomal disorders (14), prevent dendritic pathology observed in Alzheimer's disease mouse models (15), and reduce neuronal injury in experimental brain ischemia (16,17). Although all this evidence indicates the beneficial effect of DHA and suggest a requirement of DHA accretion in neuronal cells, underlying mechanisms are not well understood.…”

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confidence: 99%

Docosahexaenoic acid: A positive modulator of Akt signaling in neuronal survival

Akbar

Calderón

Zhao

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

404

319

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Phosphatidylinositol 3-kinase [PI (3)K]/Akt signaling is a critical pathway in cell survival. Here, we demonstrate a mechanism where membrane alteration by the n-3 fatty acid status affects Akt signaling, impacting neuronal survival. Docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid highly enriched in neuronal membranes, promotes neuronal survival by facilitating membrane translocation/activation of Akt through its capacity to increase phosphatidylserine (PS), the major acidic phospholipid in cell membranes. The activation of PI (3)K and phosphatidylsinositol triphosphate formation were not affected by DHA, indicating that membrane interaction of Akt is the event responsible for the DHA effect. Docosapentaenoic acid, which replaces DHA during n-3 fatty acid deficiency, was less effective in accumulating PS and translocating Akt and thus less effective in preventing apoptosis. Consistently, in vivo reduction of DHA by dietary depletion of n-3 fatty acids decreased hippocampal PS and increased neuronal susceptibility to apoptosis in cultures. This mechanism may contribute to neurological deficits associated with n-3 fatty acid deficiency and support protective effects of DHA in pathological models such as brain ischemia or Alzheimer's disease

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confidence: 99%

Docosahexaenoic acid: A positive modulator of Akt signaling in neuronal survival

Akbar

Calderón

Zhao

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

404

319

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“…It has been shown that chronic administration of DHA to essential fatty acid-deficient young rats restores DHA levels in brain and improves memory (7). Similarly, DHA administration to ischemic rats had beneficial effect on spatial cognitive deficit (8). Moriguchi et al (9) showed also that full recovery of brain DHA in essential fatty acid-deficient rats was obtained after 8 weeks on a DHA-containing diet.…”

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confidence: 99%

Modification by docosahexaenoic acid of age-induced alterations in gene expression and molecular composition of rat brain phospholipids

Barceló‐Coblijn

Hogyes

Kitajka

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

135

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Advanced age is associated with reduced brain levels of long-chain polyunsaturated fatty acids, arachidonic acid (AA) and docosahexaenoic acid (DHA). Memory impairment is also a common phenomenon in this age. Two-year-old, essential fatty acid-sufficient rats were fed with fish oil (11% DHA) for 1 month, and fatty acid as well as molecular composition of the major phospholipids, phosphatidylcholine and phosphatidylethanolamine (PE), was compared with that of 2-month-old rats on the same diet. DHA but not AA was significantly reduced in brains of old rats but was restored to the level of young rats when they received rat chow fortified with fish oil. This effect was pronounced with diacyl 18:0͞22:6 PE species, whereas levels of 18:1͞22:6 and 16:0͞22:6 remained unchanged in all of the three PE subclasses. Fish oil reduced the AA in the old rat brains, diacyl and alkenylacyl 18:0͞20:4 PE being most affected. Phosphatidylcholines gave less pronounced response. Six genes were up-regulated, whereas no significant changes were observed in brains of old rats receiving fish oil for 1 month. None of them except synuclein in young rat brains could be related to mental functions. Old rats on the fish-oil diet did not perform better in Morris water maze test than the control ones. A 10% increase in levels of diacyl 18:0͞22:6 PE in young rat brains resulted in a significant improvement of learning capacity. The results are interpreted in terms of the roles of different phospholipid molecular species in cognitive functions coupled with differential responsiveness of the genetic machinery of neurons to n-3 polyunsaturated fatty acids.B rain is one of the organs rich in phospholipids, which provide the building blocks for different membrane structures. These phospholipids are rather rich in long-chain polyunsaturated fatty acids, particularly in docosahexaenoic acid (DHA) and arachidonic acid (AA). DHA content of brain phospholipids seems to be precisely controlled. It is determined during pregnancy and early postnatal life (1, 2). There is a consensus that after this time it is almost impossible to alter brain fatty acid composition of adult, essential fatty acid-sufficient rats. On the other hand, any imbalance in polar head group or fatty-acid composition of structural lipids might have consequences on mental performance. Loss in DHA in brains of persons with Alzheimer's disease is accompanied with loss of memory and learning (3). In aged persons, impairment of memory also often takes place, and this is accompanied with loss of DHA in their brains (4-6). It has been shown that chronic administration of DHA to essential fatty acid-deficient young rats restores DHA levels in brain and improves memory (7). Similarly, DHA administration to ischemic rats had beneficial effect on spatial cognitive deficit (8). Moriguchi et al. (9) showed also that full recovery of brain DHA in essential fatty acid-deficient rats was obtained after 8 weeks on a DHA-containing diet. Hashimoto et al. (10) demonstrated that DHA provided protection fr...

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“…a-Linolenic acid deficiency in rats leads to decreases in the incorporation of docosahexanoyl-CoA into phospholipids and in the recycling of docosahexanoyl moieties within phospholipids (23). n-3 PUFA deficiency deteriorates learning ability (1,2), and supplementing the diet with n-3 PUFA reduces the risk of cognitive decline by occlusion (24,25). DHA deficiency is associated with some diseases such as cardiovascular disease (3), and intake of DHA inhibits fatal cardiac arrhythmias (26,27).…”

Section: Discussionmentioning

confidence: 99%

Whole-Body .BETA.-Oxidation of Docosahexaenoic Acid Is Decreased under n-3 Polyunsaturated Fatty Acid Insufficiency as Assessed by a 13CO2 Breath Test Using [U-13C]Fatty Acids

Waki

Watanabe

Ishii³

et al. 2004

J. Oleo Sci.

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The chronic administration of docosahexaenoic acid reduces the spatial cognitive deficit following transient forebrain ischemia in rats

Cited by 99 publications

References 34 publications

Docosahexaenoic acid: A positive modulator of Akt signaling in neuronal survival

Docosahexaenoic acid: A positive modulator of Akt signaling in neuronal survival

Modification by docosahexaenoic acid of age-induced alterations in gene expression and molecular composition of rat brain phospholipids

Whole-Body .BETA.-Oxidation of Docosahexaenoic Acid Is Decreased under n-3 Polyunsaturated Fatty Acid Insufficiency as Assessed by a 13CO2 Breath Test Using [U-13C]Fatty Acids

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