In vivo Cerebral Incorporation of Radiolabeled Fatty Acids after Acute Unilateral Orbital Enucleation in Adult Hooded Long-Evans Rats

Abstract

We examined effects of acute unilateral enucleation on incorporation from blood of intravenously injected unsaturated [1-14C]arachidonic acid ([14C]AA) and [1-14C]docosahexaenoic acid ([14C]DHA), and of saturated [9,10-3H]palmitic acid ([3H]PA), into visual and nonvisual brain areas of awake adult Long-Evans hooded rats. Regional cerebral metabolic rate for glucose (rCMRglc) values also were assessed with 2-deoxy-d-[1-14C]glucose ([14C]DG). One day after unilateral enucleation, an awake rat was placed in a brightly lit visual stimulation box with black and white striped walls, and a radiolabeled fatty acid was infused for 5 min or [14C]DG was injected as a bolus. [14C]DG also was injected in a group of rats kept in the dark for 4 h. Fifteen minutes after starting an infusion of a radiolabeled fatty acid, or 45 min after injecting [14C]DG, the rat was killed and the brain was prepared for quantitative autoradiography. Incorporation coefficients k* of fatty acids, or rCMRglc values, were calculated in homologous brain regions contralateral and ipsilateral to enucleation. As compared with ipsilateral regions, rCMRglc was reduced significantly (by as much as - 39%) in contralateral visual areas, including the superior colliculus, lateral geniculate body, and layers I, IV, and V of the primary (striate) and secondary (association, extrastriate) visual cortices. Enucleation did not affect incorporation of [3H]PA into contralateral visual regions, but reduced incorporation of [14C]AA and of [14C]DHA by - 18.5 to - 2.1%. Percent reductions were correlated with percent reductions in rCMRglc in most but not all regions. No effects were noted at any of nine nonvisual structures that were examined. These results indicate that enucleation acutely reduces neuronal activity in contralateral visual areas of the awake rat and that the reductions are coupled to reduced incorporation of unsaturated fatty acids into sn-2 regions of phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine. Reduced fatty acid incorporation likely reflects reduced activity of phospholipases A2 and/or phospholipase C.

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

“…When injected, [1-11 C]DHA was taken up to a greater extent in gray than white matter and varied 2-fold in gray matter regions, consistent with previous studies in rats (19,20) (Table 1). High uptake into the neocortex is consistent with evidence that incorporation of DHA occurs into phospholipids of brain synaptic membranes (21), that DHA is enriched in aminophospholipids of gray matter (55,56), and that high levels of DHA are found in gray matter (57).…”

“…High uptake into the neocortex is consistent with evidence that incorporation of DHA occurs into phospholipids of brain synaptic membranes (21), that DHA is enriched in aminophospholipids of gray matter (55,56), and that high levels of DHA are found in gray matter (57). Such uptake can be increased during neurotransmission or reduced by visual denervation (19,22,24) and also may represent active DHA metabolism during synaptogenesis and docosanoid formation.…”

“…We have developed a method to do this in unanesthetized rodents for both DHA and arachidonic acid (ARA; 20:4n-6) in which regional incorporation coefficients K* of either PUFA are imaged using quantitative autoradiography following the intravenous injection of the respective radiolabeled PUFA (13)(14)(15)(16)(17)(18)(19)(20)(21). This method has demonstrated that intravenously injected radiolabeled DHA or ARA is rapidly incorporated mainly into the stereospecifically numbered (sn)-2 position of different brain phospholipids (22,23).…”

Brain Incorporation of [11C]Arachidonic Acid in Young Healthy Humans Measured with Positron Emission Tomography

“…However, because of the involvement of AA in neural functions other than signal transduction, such as membrane synthesis and remodeling (Noronha et al, 1990;Grange et al, 1995;Contreras et al, 1999;Rapoport, 1999), K* is not expected to be entirely specific to the PLA 2 signaling system. To control for the fraction of the AA signal unrelated to PLA 2 activity, PA, a saturated fatty acid that is incorporated in the sn-1 position of membrane phospholipids and is not released by PLA 2 , has been used Wakabayashi et al, 1994;Rapoport, 1999). K* can be used to estimate the net rate of incorporation of AA into brain by multiplication with the plasma unlabeled AA concentration (Rapoport et al, 2001).…”

“…First, AA incorporation was substantially reduced by pharmacological inhibition of PLA 2 (Grange et al, 1998). Decreased K* values were detected selectively in contralateral visual structures after acute unilateral visual deprivation (Wakabayashi et al, 1994). In addition, K* increased in response to arecoline, a muscarinic agonist (DeGeorge et al, 1989).…”