Imaging incorporation of circulating docosahexaenoic acid into the human brain using positron emission tomography

Docosahexaenoic acid (DHA; 22:6n-3) is a critical constituent of the brain, but its metabolism has not been measured in the human brain in vivo. In monkeys, using positron emission tomography (PET), we first showed that intravenously injected [1-11C]DHA mostly entered nonbrain organs, with ∼0.5% entering the brain. Then, using PET and intravenous [1-11C]DHA in 14 healthy adult humans, we quantitatively imaged regional rates of incorporation (K*) of DHA. We also imaged regional cerebral blood flow (rCBF) using PET and intravenous [15O]water. Values of K* for DHA were higher in gray than white matter regions and correlated significantly with values of rCBF in 12 of 14 subjects despite evidence that rCBF does not directly influence K*. For the entire human brain, the net DHA incorporation rate Jin, the product of K*, and the unesterified plasma DHA concentration equaled 3.8 ± 1.7 mg/day. This net rate is equivalent to the net rate of DHA consumption by brain and, considering the reported amount of DHA in brain, indicates that the half-life of DHA in the human brain approximates 2.5 years. Thus, PET with [1-11C]DHA can be used to quantify regional and global human brain DHA metabolism in relation to health and disease. Docosahexaenoic acid (DHA; 22:6n-3) is a critical constituent of the brain, but its metabolism has not been measured in the human brain in vivo. In monkeys, using positron emission tomography (PET), we first showed that intravenously injected [1-11C]DHA mostly entered nonbrain organs, with ∼0.5% entering the brain. Then, using PET and intravenous [1-11C]DHA in 14 healthy adult humans, we quantitatively imaged regional rates of incorporation (K*) of DHA. We also imaged regional cerebral blood flow (rCBF) using PET and intravenous [15O]water. Values of K* for DHA were higher in gray than white matter regions and correlated significantly with values of rCBF in 12 of 14 subjects despite evidence that rCBF does not directly influence K*. For the entire human brain, the net DHA incorporation rate Jin, the product of K*, and the unesterified plasma DHA concentration equaled 3.8 ± 1.7 mg/day. This net rate is equivalent to the net rate of DHA consumption by brain and, considering the reported amount of DHA in brain, indicates that the half-life of DHA in the human brain approximates 2.5 years. Thus, PET with [1-11C]DHA can be used to quantify regional and global human brain DHA metabolism in relation to health and disease. The nutritionally essential n-3 PUFA, docosahexaenoic acid (DHA; 22:6n-3), is found in high concentrations in vertebrate brain and is reported to influence cell membrane fluidity, enzyme activity (1Vaidyanathan V.V. Rao K.V. Sastry P.S. Regulation of diacylglycerol kinase in rat brain membranes by docosahexaenoic acid.Neurosci. Lett. 1994; 179: 171-174Crossref PubMed Scopus (51) Google Scholar), ion channels (2Poling J.S. Karanian J.W. Salem Jr., N. Vicini S. Time- and voltage-dependent block of delayed rectifier potassium channels by docosahexaenoic acid.Mol. Pharmacol. 1995; 47: 381-390PubMed Google Scholar), and neuroreceptors and their signaling (3Delion S. Chalon S. Guilloteau D. Besnard J.C. Durand G. alpha-Linolenic acid dietary deficiency alters age-related changes of dopaminergic and serotoninergic neurotransmission in the rat frontal cortex.J. Neurochem. 1996; 66: 1582-1591Crossref PubMed Scopus (309) Google Scholar, 4Litman B.J. Mitchell D.C. A role for phospholipid polyunsaturation in modulating membrane protein function.Lipids. 1996; 31: S193-S197Crossref PubMed Google Scholar–5Chalon S. Delion-Vancassel S. Belzung C. Guilloteau D. Leguisquet A.M. Besnard J.C. Durand G. Dietary fish oil affects monoaminergic neurotransmission and behavior in rats.J. Nutr. 1998; 128: 2512-2519Crossref PubMed Scopus (236) Google Scholar). When released from membrane phospholipid by a phospholipase A2 (PLA2), unesterified DHA can act as a second messenger or can be metabolized to bioactive docosanoids and other products (6Green J.T. Orr S.K. Bazinet R.P. The emerging role of group VI calcium-independent phospholipase A2 in releasing docosahexaenoic acid from brain phospholipids.J. Lipid Res. 2008; 49: 939-944Abstract Full Text Full Text PDF PubMed Scopus (98) Google Scholar, 7Lukiw W.J. Cui J.G. Marcheselli V.L. Bodker M. Botkjaer A. Gotlinger K. Serhan C.N. Bazan N.G. A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease.J. Clin. Invest. 2005; 115: 2774-2783Crossref PubMed Scopus (716) Google Scholar, 8Contreras M.A. Greiner R.S. Chang M.C. Myers C.S. Salem Jr., N. Rapoport S.I. Nutritional deprivation of alpha-linolenic acid decreases but does not and of docosahexaenoic acid and in rat Neurochem. PubMed Scopus Google M. M. G. Docosahexaenoic acid and acid in rat brain is by of phospholipase A2 and is by and Pharmacol. PubMed Scopus Google Scholar). dietary n-3 is to be to brain n-3 deprivation in to and n-3 in and in Clin. Nutr. 2008; PubMed Scopus Google Scholar, S. C. a for of and Full Text Full Text PDF PubMed Scopus Google D. M. Jr., evidence for and in Clin. PubMed Scopus Google Scholar). the role of in brain and be to be to quantitatively brain metabolism in vivo. We a to in for DHA and acid in regional incorporation K* of imaged using the intravenous of the Rapoport S.I. injected acid and acid in of PubMed Scopus Google Scholar, Rapoport S.I. A for regional in incorporation and brain and critical Res. Res. PubMed Scopus Google Scholar, S.I. D. C. Chang In of acid incorporation brain to and N. PubMed Scopus Google Scholar, M.C. S. M.A. incorporation of in and monkeys, measured with positron emission Res. PubMed Scopus Google Scholar, S.I. Chang M.C. K. D. A. M. In of phospholipase signaling in human brain using acid and positron emission tomography Neurochem. Google Scholar, S.I. Chang M.C. and of essential in Lipid Res. Full Text Full Text PDF PubMed Google Scholar, S. Rapoport S.I. In cerebral incorporation of in adult rats.J. 1994; PubMed Scopus Google Scholar, S. Chang Rapoport S.I. In of brain incorporation of and of and of deprivation in Res. 1995; PubMed Scopus Google Rapoport S.I. for the of docosahexaenoic acid in the Res. PubMed Scopus Google Scholar). This has that intravenously injected DHA or is the of brain S. Rapoport S.I. brain incorporation of intravenously in rats.J. Neurochem. PubMed Scopus Google Scholar, S. Rapoport S.I. in rates of incorporation of intravenously injected of and brain in 1994; PubMed Scopus Google Scholar). This has also that intravenously injected DHA or incorporation is membrane of a to and that incorporation can be by of a or by of to the S.I. Chang M.C. and of essential in Lipid Res. Full Text Full Text PDF PubMed Google Scholar, Rapoport S.I. for the of docosahexaenoic acid in the Res. PubMed Scopus Google Scholar, Rapoport S.I. in incorporation of acid from blood rat brain and Neurochem. 1996; PubMed Scopus Google Scholar, Chang M.C. a phospholipase A2 incorporation and in brain of the Res. 1998; PubMed Scopus Google Scholar). incorporation brain phospholipid is by changes in regional cerebral blood flow incorporation brain phospholipid brain metabolism Rapoport S.I. A for regional in incorporation and brain and critical Res. Res. PubMed Scopus Google Scholar, M.C. S. M.A. incorporation of in and monkeys, measured with positron emission Res. PubMed Scopus Google Scholar, S. Rapoport S.I. brain incorporation of intravenously in rats.J. Neurochem. PubMed Scopus Google Scholar). The of brain DHA metabolism the of the of a PET The product of the regional incorporation K* and the unesterified concentration in plasma net incorporation rate the regional rate of of the of that is metabolized in brain and from brain S.I. Chang M.C. and of essential in Lipid Res. Full Text Full Text PDF PubMed Google Scholar). This is the other of plasma in were not to to brain Bazinet R.P. The is not for brain acid Lipid Res. 2008; 49: Full Text Full Text PDF PubMed Scopus Google Scholar, D. Rapoport S.I. evidence for incorporation of acid from plasma brain of adult Lipid Res. Full Text PDF PubMed Google and of and of DHA entering the adult brain by metabolism and not to or DHA Jr., J.C. K. Chang Rapoport S.I. Bazinet R.P. of acid is a of the in brain of adult PubMed Scopus Google Scholar, Jr., J.C. K. Chang Rapoport S.I. alpha-Linolenic acid does not to docosahexaenoic acid brain of adult a in docosahexaenoic Neurochem. 2005; PubMed Scopus Google Scholar, Salem Jr., N. does the brain its docosahexaenoic of dietary alpha-linolenic docosahexaenoic and in the Res. 2005; PubMed Scopus Google J.T. of is a quantitatively of in the rat Neurochem. 1998; PubMed Scopus Google Scholar). Thus, for DHA to the rate of DHA from brain, of DHA in Jr., J.C. K. Rapoport S.I. of docosahexaenoic acid in rat brain by of deprivation of n-3 Neurochem. PubMed Scopus Google Scholar). K* and in can of brain consumption of the in relation to and and nutritionally consumption rates be used to dietary of the brain. In of the of to brain and and of evidence that human brain and human can be by the dietary we of to in to quantitatively regional metabolism in the human brain. we first a for and DHA M.A. S. N. Rapoport S.I. phospholipid for the Scholar, M.A. N. of Scopus Google Scholar). 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Chang Rapoport S.I. alpha-Linolenic acid does not to docosahexaenoic acid brain of adult a in docosahexaenoic Neurochem. 2005; PubMed Scopus Google Scholar, Jr., J.C. K. Rapoport S.I. of docosahexaenoic acid in rat brain by of deprivation of n-3 Neurochem. PubMed Scopus Google Scholar). The rate in for the human brain, ± is equivalent to a DHA consumption rate of 3.8 ± 1.7 mg/day. by the reported amount of DHA in the human brain M. of in the brain, and of with Res. PubMed Scopus Google Scholar), DHA rate incorporation of equivalent to a half-life of the from be a half-life of 2.5 first using that brain DHA by of its from We human brain be to a in brain DHA but is dietary n-3 deprivation for a to brain For of dietary n-3 deprivation in the rat a in brain DHA and behavior Jr., J.C. K. Rapoport S.I. of docosahexaenoic acid in rat brain by of deprivation of n-3 Neurochem. PubMed Scopus Google Scholar, Jr., J.C. K. M. D. Rapoport S.I. of n-3 acid deprivation and in rats.J. Lipid Res. 47: Full Text Full Text PDF PubMed Scopus Google Scholar). A half-life measured in to that of brain DHA concentration dietary not be in is measured in A DHA half-life in also to the of reported of dietary DHA in with D. M. Jr., evidence for and in Clin. PubMed Scopus Google Scholar). not in the DHA concentration of brain the for a of n-3 influence M. R.S. and 1998; Full Text PDF PubMed Google Scholar). dietary DHA the of membranes in regions of the adult brain or influence and D.C. adult Lett. PubMed Scopus Google Scholar). In the adult to neural and changes in in to dietary S. and of in the adult 2008; PubMed Scopus Google Scholar, M. R.S. Regulation of and by and PubMed Scopus Google Scholar). When [1-11C]DHA to a in gray than white matter and in gray matter with in S. Rapoport S.I. In cerebral incorporation of in adult rats.J. 1994; PubMed Scopus Google Scholar, S. Chang Rapoport S.I. In of brain incorporation of and of and of deprivation in Res. 1995; PubMed Scopus Google the is with evidence that incorporation of DHA of brain membranes Rapoport S.I. for the of docosahexaenoic acid in the Res. PubMed Scopus Google Scholar), that DHA is in of gray matter and G. of in Scholar, Jr., N. J.S. and of of brain PubMed Scopus Google Scholar), and that high of DHA found in gray matter J.T. The influence of docosahexaenoic acid and acid in 2005; PubMed Scopus Google Scholar). can be neurotransmission or by S. Rapoport S.I. In cerebral incorporation of in adult rats.J. 1994; PubMed Scopus Google Scholar, S. Rapoport S.I. brain incorporation of intravenously in rats.J. Neurochem. PubMed Scopus Google Scholar, Rapoport S.I. in incorporation of acid from blood rat brain and Neurochem. 1996; PubMed Scopus Google and also DHA metabolism and The values of K* in the with for and with values for rCBF G. A. C. K. J.C. Rapoport S.I. incorporation of blood and blood flow in healthy a with Google Scholar, G. Chang M.C. M.A. M. A. C. incorporation of acid in healthy measured with positron emission PubMed Google Scholar). The the of is of the for with for A of is critical and of or of as or by cerebral G. A. C. K. J.C. Rapoport S.I. incorporation of blood and blood flow in healthy a with Google Scholar, D. Rapoport S.I. of age-related brain changes healthy and using Scholar, D. Rapoport S.I. brain metabolism is not in healthy for brain Res. PubMed Scopus Google Scholar). values for rCBF were to values reported in other gray matter ± to the reported in a PET ± G. A. C. K. J.C. Rapoport S.I. incorporation of blood and blood flow in healthy a with Google Scholar, G. Chang M.C. M.A. M. A. C. incorporation of acid in healthy measured with positron emission PubMed Google Scholar, in cerebral to changes in measured by positron emission PubMed Scopus Google Scholar). K* in global gray matter equaled ± and gray to white matter equaled ± can be with a PET K* for reported global gray matter values of and in and that the unesterified plasma concentration equaled 3.8 ± 1.7 global gray matter equaled is the for DHA ± G. A. C. K. J.C. Rapoport S.I. incorporation of blood and blood flow in healthy a with Google Scholar). This that the rate of brain consumption of is that of DHA. values of K* for DHA were significantly correlated with rCBF in 12 of the 14 This not by a of K* rCBF but by the that of regional brain K* for DHA is to the rate of DHA consumption by brain, in relation to the role of DHA in signaling and to its metabolism to docosanoids and other Rapoport S.I. for the of docosahexaenoic acid in the Res. PubMed Scopus Google Scholar, S. Rapoport S.I. brain incorporation of intravenously in rats.J. Neurochem. PubMed Scopus Google Scholar, C.N. and and Clin. Nutr. 2005; PubMed Scopus Google Scholar, N.G. The of brain and the of Scopus Google Jr., N. K. of of docosahexaenoic acid in the PubMed Scopus Google Scholar). is to brain consumption M. flow metabolism in Res. Google Scholar), is to of a of and of unesterified DHA membrane phospholipid Rapoport S.I. for of phospholipid metabolism in 1998; PubMed Scopus Google Scholar, of in neural Res. PubMed Scopus Google Scholar). K* for has been to be of changes in rCBF or in and in with M.C. S. M.A. incorporation of in and monkeys, measured with positron emission Res. PubMed Scopus Google Scholar, S. Rapoport S.I. brain incorporation of intravenously in rats.J. Neurochem. PubMed Scopus Google Scholar, G. G. J.S. D. M. M. in with acid and 2008; 49: PubMed Scopus Google Scholar). The for is the of unesterified to and from plasma as blood the brain, in a incorporation that is to Rapoport S.I. A for regional in incorporation and brain and critical Res. Res. PubMed Scopus Google Scholar, Rapoport S.I. of protein rates of of by Google Scholar). A and K* used to the activity The that not in the This and other in intravenous of or in showed that of brain is by in brain and that the is in the brain S. Rapoport S.I. in rates of incorporation of intravenously injected of and brain in 1994; PubMed Scopus Google Scholar, K. Rapoport S.I. acid incorporation and activity intravenous of unesterified in the Neurochem. 1994; PubMed Scopus Google Scholar). In and injected with DHA and a plasma and to brain the and other that its to brain is for of the brain J.G. Rapoport S.I. of to regional brain metabolism in rats.J. Res. PubMed Scopus Google Scholar). In of plasma intravenous [1-11C]DHA in the plasma brain does not in or G. Chang M.C. M.A. M. A. C. incorporation of acid in healthy measured with positron emission PubMed Google Scholar, J.G. Rapoport S.I. of to regional brain metabolism in rats.J. Res. PubMed Scopus Google Scholar), to brain is The that we a of subjects to the of the that is used to the [1-11C]DHA the the we found that but of the in the acid DHA. not to the in the the from the [1-11C]DHA for the that of the [1-11C]DHA the first the of we to be the to of the of In with the of PET and intravenously injected that unesterified DHA is by the human brain a global rate in healthy subjects of 3.8 ± 1.7 mg/day. PET a of regional incorporation of unesterified DHA brain and be used in the to of and brain DHA The also be used to the regional brain DHA consumption by or S. Rapoport S.I. brain incorporation of intravenously in rats.J. Neurochem. PubMed Scopus Google Scholar), using with of as has been with G. G. M. J.S. K. M. M. acid in the human brain by of positron emission PubMed Scopus Google Scholar). a by the and of the of PET were in monkeys, to and human of intravenously injected [1-11C]DHA G. Chang M.C. M.A. M. A. C. incorporation of acid in healthy measured with positron emission PubMed Google Scholar). were in the using a A intravenous of were the activity for from the for were and the by the to a The for to and the by and by injected to the that to For the of the by the of from the for a were from the with for in 1996; Google using and other from the and as as other of Scholar, of the of using concentration of with of Scholar). with PET in the brain, and of of the activity were in the of activity of and the that the human to Jr., J.C. K. M. D. Rapoport S.I. of n-3 acid deprivation and in rats.J. Lipid Res. 47: Full Text Full Text PDF PubMed Scopus Google Scholar), G. G. M. J.S. K. M. M. acid in the human brain by of positron emission PubMed Scopus Google Scholar), Chang M.C. a phospholipase A2 incorporation and in brain of the Res. 1998; PubMed Scopus Google Scholar), Rapoport S.I. in incorporation of acid from blood rat brain and Neurochem. 1996; PubMed Scopus Google Scholar), and S. Rapoport S.I. in rates of incorporation of intravenously injected of and brain in 1994; PubMed Scopus Google Scholar), with of of to the critical 12 human subjects to of [1-11C]DHA a of to the as the critical for is used for in a is used for The and for and and the of the of PET for This used the of the the of