Metabolic disturbances of synaptosomes isolated from ischemic gerbil brain

Abstract

The effects of cerebral ischemia, induced for 10 min by bilateral common carotid ligation in the Mongolian gerbil, on the brain and synaptosomal content of phospholipids and free fatty acids were measured. Moreover, the incorporation of arachidonic acid and oleoyl-CoA into phospholipids, as well as the respiration and the accumulation of 45Ca, norepinephrine, dopamine, choline, glutamate, and gamma-aminobutyrate in the ischemic brain synaptosomal fraction were studied. Analyses of lipids showed a drop in phospholipids content with concomitant increase of lysocompounds and free fatty acids in ischemic cerebral cortex. Disturbances in lipid metabolism including rapid phospholipids hydrolysis and changes in the incorporation of arachidonic acid into inositol and choline phosphoglycerides were also shown in the synaptosomal fraction of ischemic brain. The uptake of neurotransmitter substances, expressed as a percent of control value, was reduced 21% for norepinephrine, 40% for dopamine, 20% for choline, 24% for glutamate and 13% for gamma-aminobutyrate in ischemic synaptosomes. There was no significant effect of ischemia on synaptosomal respiration and 45Ca uptake in both control and high potassium media. The inhibition of neurotransmitter uptake in ischemic brain synaptosomes may be caused by the disturbance of fatty acid metabolism.

Effect of Hydroperoxy Fatty Acids on Acylation and Deacylation of Arachidonoyl Groups in Synaptic Phospholipids

“…In contrast, some stimulatory effect occurred. Interestingly, this observation complements the finding of Domanska-Janik et al (1985) who have shown that the impaired ability to acylate phospholipids of postischemic synaptosomes was completely abolished if acyl-CoA was used as a substrate. It should be noted, however, that incorporation of the label into synaptic phospholipids from arachidonoyl-CoA was several-fold lower than that when acyl-CoA was generated in situ.…”

Differential Changes in Phosphorylation of Tau at PHF-1 and 12E8 Epitopes During Brain Ischemia and Reperfusion in Gerbils

“…This rapid recovery coincides with near complete recovery of the ATP and creatine phosphate levels reported in gerbil brain [1]. It is unclear whether similar mechanisms caused the hyperphosphorylation of the PHF-1 site 3 and 7 days postischemia since sub-normal rather than elevated ATP/ GTP levels have been described in gerbils 3 days after reperfusion [2].…”

“…It is followed by the depletion of high-energy phosphates such as creatine phosphate and ATP, an accumulation of lactate, an increase in the intracellular concentration of Ca 2+ , and compromised integrity of the neuronal cytoskeleton [1,2]. Transient global ischemia is associated with shortterm damage occurring within a few hours of blood recirculation and long-term injury induced by multiple factors including oxidative stress [3].…”

“…The effects of ischemia and reperfusion on tau metabolism have been studied in rats [19,20] and dogs [21] but not in gerbils. Yet gerbils are a long established model of reversible ischemia [22][23][24] used in a number of biochemical studies [1][2][3][4][5]. Bilateral occlusion of the common carotid arteries in the gerbil brain causes a significant reduction in the blood flow difficult to achieve in other animal species.…”