Neurobehavioral aspects of omega-3 fatty acids: possible mechanisms and therapeutic value in major depression Alternative Medicine Review - Find Artic
Neurobehavioral aspects of omega-3 fatty acids: possible mechanisms and therapeutic value in major depression Alternative Medicine Review - Find Articles
Omega-3 fatty acids are an essential component of CNS membrane phospholipid-acyl chains and, as such, are critical to the dynamic structure of neuronal membranes. (3) DHA is continuously secreted by astrocytes, bathing the neuron in omega-3 fatty acid. (58) The binding of serotonin to the astroglial 5HT2A receptor can mobilize DHA to supply the neuron. (59) Alterations in membrane lipids can alter function by changing fluidity. Proteins are embedded in the lipid bi-layer and the conformation or quaternary structure of these proteins appears to be sensitive to the lipid microenvironment. The proteins in the bi-layer have critical cellular functions, acting as receptors, enzymes, and transporters. (60-64) In addition, EFAs can act as sources for second messengers within and between neurons. (65) An optimal fluidity is required for neurotransmitter binding and the signaling within the cell. (66) Omega-3 fatty acids can alter neuronal fluidity by displacing cholesterol from the membrane. (67)
It is not surprising there are functional consequences when animals are fed a diet deficient in omega-3 fatty acids (Table 3). Reduction in omega-3 intake (in the form of ALA) results in a reduction of omega-3 content throughout the brain cells and organelles along with a compensatory rise in omega-6 fatty acid content. This alteration is accompanied by a 40-percent reduction in the [Na.sup.+][K.sup.+] ATPase of nerve terminals, an enzyme that controls ion transport produced by nerve transmission and that consumes half the energy used by the brain. (63) There is also a 20-percent reduction in 5'-nucleotidase activity, a decrease in fluidity in the surface polar part of the membrane, (63) and a significant reduction in the cell body size of the hippocampal CA1 pyramidal neuron. (68) A 30-percent reduction in the average densities of synaptic vesicles in the terminals of the hippocampal CA1 region has also been observed as a result of an omega-3 deficiency combined with a learning task. (69) Deficiency of omega-3s also results in a 30-35 percent reduction in phosphatidylserine (PS) in the rat brain cortex, brain mitochondria, and olfactory bulb. (70) On the other hand, fish oil supplemented to rats can increase PS composition of the cerebral membrane. (71) This is an interesting finding, given research showing that PS has antidepressant activity in adults. (72,73) PS can activate various enzymes, including protein kinase C, [Na.sup.+][K.sup.+] ATPase, and tyrosine hydroxylase, as well as regulating calcium uptake. It is therefore suggested that altering PS in cerebral membranes can alter neurotransmission. (71)
A number of studies have specifically examined the effect of an omega-3 deficient diet on dopamine and serotonin levels in animals. Animals on such a diet have a reduction in the dopaminergic vesicle pool (74) along with a 40-60 percent decrease in the amount of dopamine in the frontal cortex and an increase in the NA, (75,76) alterations strikingly similar to the animal models of depression described above. Although overall dopamine levels in the NA are higher in an omega-3 deficiency and the animal model of depression, function of the NA-dopaminergic system appears to be abnormal in both. In an omega-3 deficiency, the release of dopamine from the vesicular storage pool under tyramine stimulation is 90-percent lower than in rats receiving an adequate omega-3 intake. (74) In the animal model of depression, although overall NA-dopamine levels are higher, the extracellular levels of dopamine in the NA are lower than normal controls and do not respond to normal serotonin stimulation. (77)
Omega-3 fatty acids are an essential component of CNS membrane phospholipid-acyl chains and, as such, are critical to the dynamic structure of neuronal membranes. (3) DHA is continuously secreted by astrocytes, bathing the neuron in omega-3 fatty acid. (58) The binding of serotonin to the astroglial 5HT2A receptor can mobilize DHA to supply the neuron. (59) Alterations in membrane lipids can alter function by changing fluidity. Proteins are embedded in the lipid bi-layer and the conformation or quaternary structure of these proteins appears to be sensitive to the lipid microenvironment. The proteins in the bi-layer have critical cellular functions, acting as receptors, enzymes, and transporters. (60-64) In addition, EFAs can act as sources for second messengers within and between neurons. (65) An optimal fluidity is required for neurotransmitter binding and the signaling within the cell. (66) Omega-3 fatty acids can alter neuronal fluidity by displacing cholesterol from the membrane. (67)
It is not surprising there are functional consequences when animals are fed a diet deficient in omega-3 fatty acids (Table 3). Reduction in omega-3 intake (in the form of ALA) results in a reduction of omega-3 content throughout the brain cells and organelles along with a compensatory rise in omega-6 fatty acid content. This alteration is accompanied by a 40-percent reduction in the [Na.sup.+][K.sup.+] ATPase of nerve terminals, an enzyme that controls ion transport produced by nerve transmission and that consumes half the energy used by the brain. (63) There is also a 20-percent reduction in 5'-nucleotidase activity, a decrease in fluidity in the surface polar part of the membrane, (63) and a significant reduction in the cell body size of the hippocampal CA1 pyramidal neuron. (68) A 30-percent reduction in the average densities of synaptic vesicles in the terminals of the hippocampal CA1 region has also been observed as a result of an omega-3 deficiency combined with a learning task. (69) Deficiency of omega-3s also results in a 30-35 percent reduction in phosphatidylserine (PS) in the rat brain cortex, brain mitochondria, and olfactory bulb. (70) On the other hand, fish oil supplemented to rats can increase PS composition of the cerebral membrane. (71) This is an interesting finding, given research showing that PS has antidepressant activity in adults. (72,73) PS can activate various enzymes, including protein kinase C, [Na.sup.+][K.sup.+] ATPase, and tyrosine hydroxylase, as well as regulating calcium uptake. It is therefore suggested that altering PS in cerebral membranes can alter neurotransmission. (71)
A number of studies have specifically examined the effect of an omega-3 deficient diet on dopamine and serotonin levels in animals. Animals on such a diet have a reduction in the dopaminergic vesicle pool (74) along with a 40-60 percent decrease in the amount of dopamine in the frontal cortex and an increase in the NA, (75,76) alterations strikingly similar to the animal models of depression described above. Although overall dopamine levels in the NA are higher in an omega-3 deficiency and the animal model of depression, function of the NA-dopaminergic system appears to be abnormal in both. In an omega-3 deficiency, the release of dopamine from the vesicular storage pool under tyramine stimulation is 90-percent lower than in rats receiving an adequate omega-3 intake. (74) In the animal model of depression, although overall NA-dopamine levels are higher, the extracellular levels of dopamine in the NA are lower than normal controls and do not respond to normal serotonin stimulation. (77)
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