Polyunsaturated fatty acids modulate sodium and calcium currents in CA1 neurons.

Vreugdenhil, Martin; Bruehl, Claus; Voskuyl, R.A.; Kang, Jing; Leaf, Alexander; Wadman, W.J.

doi:10.1073/pnas.93.22.12559

Cited by 276 publications

(193 citation statements)

References 31 publications

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“…This fact is due to their favorable biophysical properties such as high motility and motional freedom (20)(21)(22)(23). DHAcontaining phospholipid molecular species might affect the blood-brain barrier (24), neurotransmission (4,22,25), or ionic channels (26,27). However, all of our knowledge on biophysical properties of membranes is based on results obtained on choline phosphoglycerides.…”

Section: Molecular Speciesmentioning

confidence: 96%

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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Section: Molecular Speciesmentioning

confidence: 96%

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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“…In young animals oxidative stress can raise the level of brain cholesterol to the level of aged rats [29]. One possible mechanism to the harmful effects of the oxidative stress is the finding that the stress induced an increase in lipid peroxidation by ATP via Ca 2+ [22,26,120]. Some successful efforts to correct the effects of the stress via special food supplements have been reported [11,12,[57][58][59][60]119], including PUFA supplements that can reverse the alcohol effects on the membrane [81], and increase the activity of certain membrane bound enzymes in different brain areas [110].…”

Section: Oxidative Stress-free Radicalsmentioning

confidence: 99%

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

Yehuda¹,

Rabinovitz²,

Carasso³

et al. 2002

Neurobiology of Aging

353

200

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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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“…Physiologic experiments, for example, have demonstrated that DHA or an anandamide analog of DHA has a potent effect on the K + channel (91)(92)(93). Leaf and co-workers showed that the nonesterified form of DHA has a potent effect on Na + (94)(95)(96) and Ca 2+ channels (96,97). Also, synaptic transmission (98) and long-term potentiation (99,100) in the hippocampus as well as N-methyl-D-aspartate responses in the cerebral cortex (101) are altered by DHA.…”

Section: Mechanisms Of Action Of Dhamentioning

confidence: 99%

Mechanisms of action of docosahexaenoic acid in the nervous system

Salem

Litman

Kim

et al. 2001

Lipids

825

508

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This review describes (from both the animal and human literature) the biological consequences of losses in nervous system docosahexaenoate (DHA). It then concentrates on biological mechanisms that may serve to explain changes in brain and retinal function. Brief consideration is given to actions of DHA as a nonesterified fatty acid and as a docosanoid or other bioactive molecule. The role of DHA-phospholipids in regulating G-protein signaling is presented in the context of studies with rhodopsin. It is clear that the visual pigment responds to the degree of unsaturation of the membrane lipids. At the cell biological level, DHA is shown to have a protective role in a cell culture model of apoptosis in relation to its effects in increasing cellular phosphatidylserine (PS); also, the loss of DHA leads to a loss in PS. Thus, through its effects on PS, DHA may play an important role in the regulation of cell signaling and in cell proliferation. Finally, progress has been made recently in nuclear magnetic resonance studies to delineate differences in molecular structure and order in biomembranes due to subtle changes in the degree of phospholipid unsaturation.Paper no. L8776 in Lipids 36, 945-959 (September 2001)

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Polyunsaturated fatty acids modulate sodium and calcium currents in CA1 neurons.

Cited by 276 publications

References 31 publications

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

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

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

Mechanisms of action of docosahexaenoic acid in the nervous system

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