Neural stimuli for HUFA turnover

    Li(+) reduces the turnover rate of arachidonic acid (AA) by 80% in brain phospholipids of the awake rat, without changing turnover rates of docosahexaenoic or palmitic acid. The reduced AA turnover was accompanied by down-regulation of gene expression and protein levels of an AA-specific cytosolic phospholipase A(2) (cPLA(2)). Chronically administered valproic acid (VPA) significantly decreased AA turnover within brain phospholipids (by 28-33%), although it had no effect on cPLA(2) protein levels. Chang MC, Contreras MA, Rosenberger TA, Rintala JJ, Bell JM, Rapoport SI. Chronic valproate treatment decreases the in vivo turnover of arachidonic acid in brain phospholipids: a possible common effect of mood stabilizers. J Neurochem 2001 May;77(3):796-803.

    Using [(3)H] arachidonic acid ([(3)H] -AA), we examined the brain dopamine system in rats with a chronic unilateral 6-hydroxydopamine lesion of the substantia nigra pars compacta, a model of Parkinson's disease. Results with different drugs suggest up-regulation in basal ganglia and cortical dopamine circuits mediated by phospholipase A(2) ipsilateral to the substantia nigra lesion. Hayakawa T, Chang MC, Rapoport SI, Appel NM. Selective dopamine receptor stimulation differentially affects [3H]-arachidonic acid incorporation, a surrogate marker for phospholipase A2-mediated neurotransmitter signal transduction, in a rodent model of Parkinson's disease. J Pharmacol Exp Ther 2001 Mar;296(3):1074-84.

    A method and model are described to quantify in vivo turnover rates and half-lives of fatty acids within brain phospholipids. These "kinetic" parameters can be calculated by operational equations from measured rates of incorporation of intravenously injected fatty acid radiotracers into brain phospholipids. Some calculated fatty acid half-lives are minutes to hours, consistent with active participation of phospholipids in brain function and structure. Rapoport SI. In vivo fatty acid incorporation into brain phospholipids in relation to signal transduction and membrane remodeling. Neurochem Res 1999 Nov;24(11):1403-15

    Ischemia-reperfusion increased the rate of incorporation of unlabeled AA from brain arachidonoyl-CoA by a factor of 2.3-3.3 compared with the control rate; this factor was further augmented to 3.6-5.0 by pretreatment with Ginkgo biloba extract (EGb 761). There is selective reincorporation of AA compared with Pam into brain phospholipids following ischemia. EGb 761 further accelerates AA reincorporation, potentially reducing neurotoxic effects of prolonged exposure of brain to high concentrations of AA and its metabolites. Rabin O, Drieu K, Grange E, Chang MC, Rapoport SI, Purdon AD. Effects of EGb 761 on fatty acid reincorporation during reperfusion following ischemia in the brain of the awake gerbil. Mol Chem Neuropathol 1998 May;34(1):79-10.

    Pulse labeling with [3H]-arachidonic acid ([3H]-AA) reflects regional changes in neurotransmitter signal transduction by phospholipase A2. In a rat model of Parkinson's disease, increased [3H]-AA incorporation likely reflects disinhibition of basal ganglia and cortical circuits secondary to absent inhibitory nigrostriatal dopaminergic input. Hayakawa T, Chang MC, Bell JM, Seeman R, Rapoport SI, Appel NM. Fatty acid incorporation depicts brain activity in a rat model of Parkinson's disease. Brain Res 1998 Oct 5;807(1-2):177-181.

    The incorporation coefficient for [1-14C]-AA was approximately 2-fold higher in microvessels isolated from arecoline-injected than from sham-injected animals. The data demonstrate that activation of cholinergic pathways within the rat CNS stimulates arachidonic acid turnover in cerebral microvessels.  Arecoline stimulation of radiolabeled arachidonate incorporation from plasma into brain microvessels of awake rat. Neurochem Res 1998 Apr;23(4):551-5 Arecoline increased [3H]-DHA entry into the synaptosomal fractions by 100% and into the microsomal fraction by 50%. In these fractions 60%-65% of the [3H]-DHA was in phospholipid, the rest in free fatty acid and diacylglycerol. In contrast, arecoline did not change [3H]-palmitate incorporation into any brain fraction. These results demonstrate that plasma [3H]-DHA is selectively incorporated into synaptic membrane phospholipids of the rat brain in response to cholinergic activation. Williams WM, Hayakawa T, Grange E, Rapoport SI. Jones CR, Arai T, Rapoport SI. Evidence for the involvement of docosahexaenoic acid in cholinergic stimulated signal transduction at the synapse. Neurochem Res 1997 Jun;22(6):663-70.