Biomedical subjects

Kaizong Ma

Publications and source records attributed to Kaizong Ma.

10 recordsLinked to original sources

PubMed2007

Altered brain lipid composition in cyclooxygenase-2 knockout mouse.

Cyclooxygenase (COX)-2 plays an important role in brain arachidonic acid (20:4n-6) metabolism, and its expression is upregulated in animal models of neuroinflammation and excitotoxicity. Our hypothesis was that brain lipid composition would be altered in COX-2 knockout (COX-2(-/-)) compared with wild-type (COX-2(+/+)) mice, reflecting the important role of COX-2 in brain lipid metabolism. Concentrations of different lipids were measured in high-energy microwaved brain from COX-2(-/-) and COX-2(+/+) mice. Compared with the COX-2(+/+) mouse brain, the brain of the COX-2(-/-) mouse had a statistically significant 15% increase in phosphatidylserine (PtdSer) and significant 37, 27, and 32% reductions in triacylglycerol and cholesterol concentrations and in the cholesterol-to-phospholipid ratio, respectively. The normalized concentration of palmitic acid (16:0) was increased in PtdSer, as was the brain concentration of unesterified arachidic acid (20:0). A lifetime absence of COX-2 produces multiple changes in brain lipid composition. These changes may be related to reported changes in fatty acid kinetics and in resistance to neuroinflammation and excitotoxicity in the COX-2(-/-) mouse.

Animals↗

PubMed2006

Imaging signal transduction via arachidonic acid in the human brain during visual stimulation, by means of positron emission tomography.

BACKGROUND: Arachidonic acid (AA, 20:4n-6), an important second messenger, is released from membrane phospholipid following receptor mediated activation of phospholipase A(2) (PLA(2)). This signaling process can be imaged in brain as a regional brain AA incorporation coefficient K*. HYPOTHESIS: K* will be increased in brain visual areas of subjects submitted to visual stimulation. SUBJECTS AND METHODS: Regional values of K* were measured with positron emission tomography (PET), following the intravenous injection of [1-(11)C]AA, in 16 healthy volunteers subjected to visual stimulation at flash frequencies 2.9 Hz (8 subjects) or 7.8 Hz (8 subjects), compared with the dark (0 Hz) condition. Regional cerebral blood flow (rCBF) was measured with intravenous [(15)O]water under comparable conditions. RESULTS: During flash stimulation at 2.9 Hz or 7.8 Hz vs. 0 Hz, K* was increased significantly by 2.3-8.9% in Brodmann areas 17, 18 and 19, and in additional frontal, parietal and temporal cortical regions. rCBF was increased significantly by 3.1-22%, often in comparable regions. Increments at 7.8 Hz often exceeded those at 2.9 Hz for both K* and rCBF. Decrements in both parameters also were produced, particularly in frontal brain regions. CONCLUSIONS: AA plays a role in signaling processes provoked by visual stimulation, since visual stimulation at flash frequencies of 2.9 and 7.8 Hz compared to 0 Hz modifies both K* for AA and rCBF in visual and related areas of the human brain. The two-stimulus condition paradigm of this study might be used with PET to image effects of other functional activations and of drugs on brain signaling via AA.

Adult↗

PubMed2006

Upregulated liver conversion of alpha-linolenic acid to docosahexaenoic acid in rats on a 15 week n-3 PUFA-deficient diet.

We quantified incorporation rates of plasma-derived alpha-linolenic acid (alpha-LNA, 18:3n-3) into "stable" liver lipids and the conversion rate of alpha-LNA to docosahexaenoic acid (DHA, 22:6n-3) in male rats fed, after weaning, an n-3 PUFA-adequate diet (4.6% alpha-LNA, no DHA) or an n-3 PUFA-deficient diet (0.2% alpha-LNA, no DHA) for 15 weeks. Unanesthetized rats were infused intravenously with [1-14C]alpha-LNA, and arterial plasma was sampled until the liver was microwaved at 5 min. Unlabeled alpha-LNA and DHA concentrations in arterial plasma and liver were reduced >90% by deprivation, whereas unlabeled arachidonic acid (20:4n-6) and docosapentaenoic acid (22:5n-6) concentrations were increased. Deprivation did not change alpha-LNA incorporation coefficients into stable liver lipids but increased synthesis-incorporation coefficients of DHA from alpha-LNA by 6.6-, 8.4-, and 2.3-fold in triacylglycerol, phospholipid, and cholesteryl ester, respectively. Assuming that synthesized-incorporated DHA eventually would be secreted within lipoproteins, calculated liver DHA secretion rates equaled 2.19 and 0.82 micromol/day in the n-3 PUFA-adequate and -deprived rats, respectively. These rates exceed the published rates of brain DHA consumption by 6- and 10-fold, respectively, and should be sufficient to maintain normal and reduced brain DHA concentrations, respectively, in the two dietary conditions.

Animals↗

PubMed2006

Brain elongation of linoleic acid is a negligible source of the arachidonate in brain phospholipids of adult rats.

The extent to which the adult brain can derive some of its arachidonic acid (AA) through internalized synthesis from linoleic acid (LA) is uncertain. Thus, we determined for plasma-derived LA in vivo rates for brain incorporation, beta-oxidation, and conversion to AA. Adult male unanesthetized rats, reared on a diet enriched in LA but low in AA, were infused intravenously for 5 min with [1-(14)C]LA. Timed arterial samples were collected until the animals were killed at 5 min and the brain was removed after microwaving. Within plasma lipids, >96% of radioactivity was in the form of unchanged [1-(14)C]LA, but [(14)C]AA was insignificant (<0.2%). Eighty-six percent of brain radioactivity at 5 min was present as beta-oxidation products, whereas the remainder was mainly in 'stable' phospholipid or triglyceride as LA or AA (11 and <1%, respectively). Unesterified unlabeled LA rapidly enters brain from plasma, but its incorporation into brain total phospholipid and triglyceride, in the form of synthesized AA, is <1% of the amount that enters the brain. Thus, in rats fed even a diet containing low amounts of AA, the LA that enters brain is largely beta-oxidized, and is not a major source of AA in brain.

Animals↗

PubMed2006

Measuring brain uptake and incorporation into brain phosphatidylinositol of plasma myo-[2H6]inositol in unanesthetized rats: an approach to estimate in vivo brain phosphatidylinositol turnover.

The in vivo rate of turnover of phosphatidylinositol (PtdIns) in brain is not known. In brain, certain receptor-mediated signal transduction involves metabolism of PtdIns and a method to measure its turnover in awake animals is useful in studying the effect of lithium and other therapeutic agents. In a method described here, rats were infused subcutaneously with myo-[2H6]inositol (Ins*) using an osmotic pump and, at 1 and 8 weeks, concentrations of free myo-inositol (Ins) and Ins* in plasma and brain were measured by GC-MS (chemical ionization). Also, PtdIns and PtdIns* together in brain were isolated, and Ins and Ins* from their headgroups were released enzymatically and specific activity of incorporated inositol was measured. The specific activity of inositol reached a steady state in plasma within 1 week of infusion, but not in brain even at 8 weeks. However, in brain, the specific activity of phosphatidylinositol was same as that of inositol at both time-points, suggestive of fast turnover of PtdIns. The animal experiment and the analytical methodology described here should be useful for measuring the rate of turnover of brain PtdIns in pathological and drug treatment conditions.

Animals↗

PubMed2006

Low liver conversion rate of alpha-linolenic to docosahexaenoic acid in awake rats on a high-docosahexaenoate-containing diet.

We quantified the rates of incorporation of alpha-linolenic acid (alpha-LNA; 18:3n-3) into "stable" lipids (triacylglycerol, phospholipid, cholesteryl ester) and the rate of conversion of alpha-LNA to docosahexaenoic acid (DHA; 22: 6n-3) in the liver of awake male rats on a high-DHA-containing diet after a 5-min intravenous infusion of [1-(14)C]alpha-LNA. At 5 min, 72.7% of liver radioactivity (excluding unesterified fatty acid radioactivity) was in stable lipids, with the remainder in the aqueous compartment. Using our measured specific activity of liver alpha-LNA-CoA, in the form of the dilution coefficient lambda(alpha-LNA-CoA), we calculated incorporation rates of unesterified alpha-LNA into liver triacylglycerol, phospholipid, and cholesteryl ester as 2,401, 749, and 9.6 nmol/s/g x 10(-4), respectively, corresponding to turnover rates of 3.2, 8.7, and 2.9%/min and half-lives of 8-24 min. A lower limit for the DHA synthesis rate from alpha-LNA equaled 15.8 nmol/s/g x 10(-4) (0.5% of the net in corporation rate). Thus, in rats on a high-DHA-containing diet, rates of beta-oxidation and esterification of alpha-LNA into stable liver lipids are high, whereas its conversion to DHA is comparatively low and insufficient to supply significant DHA to the brain. High incorporation and turnover rates likely reflect a high secretion rate by liver of stable lipids within very low density lipoproteins.

Acyl Coenzyme A↗

PubMed2006

Resting and arecoline-stimulated brain metabolism and signaling involving arachidonic acid are altered in the cyclooxygenase-2 knockout mouse.

Abstract Studies were performed to determine if cyclooxygenase (COX)-2 regulates muscarinic receptor-initiated signaling involving brain phospholipase A2 (PLA2) activation and arachidonic acid (AA; 20 : 4n-6) release. AA incorporation coefficients, k* (brain [1-14C]AA radioactivity/integrated plasma radioactivity), representing this signaling, were measured following the intravenous injection of [1-14C]AA using quantitative autoradiography, in each of 81 brain regions in unanesthetized COX-2 knockout (COX-2(-/-)) and wild-type (COX-2(+/+)) mice. Mice were administered arecoline (30 mg/kg i.p.), a non-specific muscarinic receptor agonist, or saline i.p. (baseline control). At baseline, COX-2(-/-) compared with COX-2(+/+) mice had widespread and significant elevations of k*. Arecoline increased k* significantly in COX-2(+/+) mice compared with saline controls in 72 of 81 brain regions, but had no significant effect on k* in any region in COX-2(-/-) mice. These findings, when related to net incorporation rates of AA from brain into plasma, demonstrate enhanced baseline brain metabolic loss of AA in COX-2(-/-) compared with COX-2(+/+) mice, and an absence of a normal k* response to muscarinic receptor activation. This response likely reflects selective COX-2-mediated conversion of PLA2-released AA to prostanoids.

Animals↗

PubMed2005

alpha-Linolenic acid does not contribute appreciably to docosahexaenoic acid within brain phospholipids of adult rats fed a diet enriched in docosahexaenoic acid.

Adult male unanesthetized rats, reared on a diet enriched in both alpha-linolenic acid (alpha-LNA) and docosahexaenoic acid (DHA), were infused intravenously for 5 min with [1-(14)C]alpha-LNA. Timed arterial samples were collected until the animals were killed at 5 min and the brain was removed after microwaving. Plasma and brain lipid concentrations and radioactivities were measured. Within plasma lipids, > 99% of radioactivity was in the form of unchanged [1-(14)C]alpha-LNA. Eighty-six per cent of brain radioactivity at 5 min was present as beta-oxidation products, whereas the remainder was mainly in 'stable' phospholipid or triglyceride as alpha-LNA or DHA. Equations derived from kinetic modeling demonstrated that unesterified unlabeled alpha-LNA rapidly enters brain from plasma, but that its incorporation into brain phospholipid and triglyceride, as in the form of synthesized DHA, is < or = 0.2% of the amount that enters the brain. Thus, in rats fed a diet containing large amounts of both alpha-LNA and DHA, the alpha-LNA that enters brain from plasma largely undergoes beta-oxidation, and is not an appreciable source of DHA within brain phospholipids.

Animals↗

PubMed2004

Half-lives of docosahexaenoic acid in rat brain phospholipids are prolonged by 15 weeks of nutritional deprivation of n-3 polyunsaturated fatty acids.

Male rat pups (21 days old) were placed on a diet deficient in n-3 polyunsaturated fatty acids (PUFAs) or on an n-3 PUFA adequate diet containing alpha-linolenic acid (alpha-LNA; 18 : 3n-3). After 15 weeks on a diet, [4,5-3H]docosahexaenoic acid (DHA; 22 : 6n-3) was injected into the right lateral cerebral ventricle, and the rats were killed at fixed times over a period of 60 days. Compared with the adequate diet, 15 weeks of n-3 PUFA deprivation reduced plasma DHA by 89% and brain DHA by 37%; these DHA concentrations did not change thereafter. In the n-3 PUFA adequate rats, DHA loss half-lives, calculated by plotting log10 (DHA radioactivity) against time after tracer injection, equaled 33 days in total brain phospholipid, 23 days in phosphatidylcholine, 32 days in phosphatidylethanolamine, 24 days in phosphatidylinositol and 58 days in phosphatidylserine; all had a decay slope significantly greater than 0 (p < 0.05). In the n-3 PUFA deprived rats, these half-lives were prolonged twofold or greater, and calculated rates of DHA loss from brain, Jout, were reduced. Mechanisms must exist in the adult rat brain to minimize DHA metabolic loss, and to do so even more effectively in the face of reduced n-3 PUFA availability for only 15 weeks.

Analysis of Variance↗

PubMed2004

Brain incorporation of 11C-arachidonic acid, blood volume, and blood flow in healthy aging: a study with partial-volume correction.

UNLABELLED: PET with 11C-arachidonic acid (AA) can be used to quantify neural signaling related to phospholipase A2 (PLA2). Animal studies suggest reduction in the activity of this signaling system with age. The aim of this study was to evaluate the effect of healthy aging on brain incorporation of 11C-AA, before and after partial-volume correction (PVC). METHODS: Absolute measurements of cerebral blood flow (CBF) were obtained in 8 young and 7 old healthy subjects (mean age +/- SD, 27 +/- 5 y and 65 +/- 9 y) with bolus injection of 15O-water. About 15 min later, dynamic 60-min 3-dimensional scans were acquired after the injection of 11C-AA. Radioactivity frames of 11C-AA were corrected for head motion and registered to magnetic resonance (MR) images. A 3-segment (3S) and a 2-segment (2S) PVC was applied pixel-by-pixel to the activity frames. For the 3S method, the white matter value was estimated using a new automatic method by extrapolating the activity values of pixels with white matter membership > 0.99. Parametric images of the brain incorporation rate of 11C-AA (K*) and cerebral blood volume (Vb), as well as CBF, were generated and regional gray matter values were obtained. RESULTS: Among cortical areas, there were no significant differences (uncorrected P < 0.05) in K* or Vb absolute values between young and old subjects before or after PVC. A significant reduction of CBF was detected in the frontal cortex of the elderly group. After normalization to the global gray average, K*, Vb, and CBF values revealed significant reductions in the frontal lobe of old subjects; none of these differences were significant after PVC. CONCLUSION: These results confirm previous PET findings that brain function at rest is minimally affected by healthy aging. Proper PVC methodology is of critical importance in accurate quantitative assessment of PET physiologic measures.

Adult↗