RESUMEN
Platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine), which is thought to be a retrograde messenger in long-term potentiation (LTP), enhances glutamate release and LTP through an action on presynaptic nerve endings. The PAF antagonist BN 52021 blocks CA1 LTP in hippocampal slices, and, when infused into rat dorsal hippocampus pre- or posttraining, blocks retention of inhibitory avoidance. Here we report that memory is affected by pre- or posttraining infusion of the PAF analog 1-O-hexadecyl-2-N-methylcarbamoyl-sn-glycerol-3-phosphocholine (mc-PAF) into either rat dorsal hippocampus, amygdala, or entorhinal cortex. Male Wistar rats were implanted bilaterally with cannulae in these brain regions. After recovery from surgery, the animals were trained in step-down inhibitory avoidance or in a spatial habituation task and tested for retention 24 h later. mc-PAF (1.0 microgram per side) enhanced retention test performance of the two tasks when infused into the hippocampus before training without altering training session performance. In addition, mc-PAF enhanced retention test performance of the avoidance task when infused into (i) the hippocampus 0 but not 60 min after training; (ii) the amygdala immediately after training; and (iii) the entorhinal cortex 100 but not 0 or 300 min after training. In confirmation of previous findings, BN 52021 (0.5 microgram per side) was found to be amnestic for the avoidance task when infused into the hippocampus or the amygdala immediately but not 30 or more minutes after training or into the entorhinal cortex 100 but not 0 or 300 min after training. These findings support the hypothesis that memory involves PAF-regulated events, possibly LTP, generated at the time of training in hippocampus and amygdala and 100 min later in the entorhinal cortex.
Asunto(s)
Amígdala del Cerebelo/fisiología , Reacción de Prevención/fisiología , Diterpenos , Hipocampo/fisiología , Memoria/fisiología , Factor de Activación Plaquetaria/farmacología , Amígdala del Cerebelo/efectos de los fármacos , Animales , Reacción de Prevención/efectos de los fármacos , Ginkgólidos , Habituación Psicofisiológica , Hipocampo/efectos de los fármacos , Técnicas In Vitro , Infusiones Parenterales , Lactonas/administración & dosificación , Lactonas/farmacología , Potenciación a Largo Plazo/efectos de los fármacos , Masculino , Memoria/efectos de los fármacos , Factor de Activación Plaquetaria/administración & dosificación , Factor de Activación Plaquetaria/antagonistas & inhibidores , Células Piramidales/efectos de los fármacos , Células Piramidales/fisiología , Ratas , Ratas Wistar , Valores de Referencia , Percepción Espacial , Factores de TiempoRESUMEN
Platelet-activating factor (PAF) is present in the brain. It enhances glutamate release and long-term potentiation (LTP) through an action on synaptic membrane receptors sensitive to the antagonist, BN 52021, and has been proposed as a retrograde messenger in the genesis of LTP. In addition, PAF has other, metabolic actions mediated by microsomal receptors sensitive to the antagonist, BN 50730. We investigated the effect on memory of the pre- or post-training infusion of BN 52021 or BN 50730 into the hippocampus and that of BN 52021 in the amygdala and the entorhinal cortex. Male Wistar rats were implanted bilaterally with cannulae aimed at these brain regions. After recovery from surgery, the animals were trained in step-down inhibitory avoidance using a 0.5-mA foot shock and tested for retention 24 h later. BN 52021 (0.5 microgram/side) was amnestic when given into the hippocampus or the amygdala either before or immediately after training but not 30 or 100 min later. BN 52021 was also amnestic when given into the entorhinal cortex 100 but not 0 or 300 min after training. Intrahippocampally administered BN 50730 had no effect on memory. The findings are compatible with the suggestion from previous findings that memory of this task depends on the generation of LTP at the time of training in hippocampus and amygdala and, 90-180 min later, in the entorhinal cortex.
Asunto(s)
Reacción de Prevención/efectos de los fármacos , Diterpenos , Lactonas/farmacología , Memoria/efectos de los fármacos , Factor de Activación Plaquetaria/antagonistas & inhibidores , Inhibidores de Agregación Plaquetaria/farmacología , Amígdala del Cerebelo/efectos de los fármacos , Animales , Ginkgólidos , Glutamatos/metabolismo , Hipocampo/efectos de los fármacos , Masculino , Ratas , Ratas Wistar , Membranas Sinápticas/efectos de los fármacosRESUMEN
The de novo biosynthesis of phospholipids and glycerides was followed in subcellular fractions from bovine retinas incubated during short periods with radioactive glycerol. The labeling of lipid classes was determined in the following fractions: rod outer segments, P(1), P(2), microsomes and soluble. A highly labeled phosphatidic acid was found in microsomal fractions with a maximum at 5 min relative to other lipids labeling. The labeling of phospholipids and glycerides from microsomes as well as from other fractions was rapid. The soluble contained minor quantities of phospholipids with high radioactivity. Using radioactive glycerol and amphiphilic drugs the rates of phosphatidic acid synthesis in microsomal membranes were assessed. Moreover, in agreement with previous studies from this laboratory showing that phosphatidic acid contains a high proportion of docosahexaenoate, it is demonstrated that this fatty acid is acylated in the biosynthetic route leading to phosphatidic acid formation. Phosphatidylserine is synthesized from radioactive serine and also through a Ca(2+) independent pathway not involving phosphatidylethanolamine. Phosphatidylethanolamine is also formed by serine decarboxylation. Amphiphilic drugs greatly stimulate phosphatidylserine synthesis. Extracellular Ca(2+) stimulates the synthesis of phosphatidylserine and its decarboxylation. Besides, Ca(2+) potentiates the phospholipid effect exerted by propranolol. The synthesis of phosphatidylinositol as well as that of other minor acidic phospholipids seems to operate in a coordinated manner under different experimental conditions. The microsomal system of the retina generates a docosahexaenoyl enriched phosphatidic acid at high rates. In addition to the turnover of different phospholipid moieties there are active pathways for the de novo biosynthesis of membrane lipids in the retina.
RESUMEN
Recent studies on the fatty acid composition and labeling by glycerol of individual molecular species of retinal phosphoglycerides are presented. Docosahexaenoate-containing species are important constituents of retina phospholipids. 22:6 and saturated fatty acids appear in similar amounts in hexaenes (nearly 50% each). Very high percentages of 22:6 and other polyenoic fatty acids are found in molecular species containing negligible amounts of saturated fatty acids, indicating the occurrence of dipolyunsaturated phosphoglycerides, including didocosahexaenoate. On the other extreme, fully saturated species occur. 22:6-containing species are synthesized at high rates in most phosphoglycerides including phosphatidylinositol, which is mainly formed by tetraenoic classes. Oligoenes and saturates are synthesized de novo and once formed they may serve as precursors of others (e.g. tetraenes) by acyl-exchange reactions. Propranolol induces rapid modifications in the de novo biosynthesis of retina glycerolipids. Oligoenes and saturates are the most stimulated species in PI and PS, and the most inhibited ones in PC. In PE, the labeling of these species is stimulated, while the polyenes are inhibited. This remarkable example of metabolic heterogeneity in a single phosphoglyceride opens new possibilities in the study of the regulation of retinal membrane lipid biosynthesis.
RESUMEN
The phospholipid composition as well as the in vivo [14C]glycerol uptake in lipids was found to be similar in the toad brain and retina. The choroid lipid labeling was markedly different. An in vitro time-course study of [14C]glycerol incorporation in toad retina lipids disclosed that under the conditions of these experiments: (1) retina is able to rapidly synthesize phosphatidic acid from the radioactive precursor; (2) the sequence phosphatidic acid-diacylglycerol-triacylglycerol operates; (3) a high rate of phosphatidylinositol de novo biosynthesis takes place; (4) phosphoglycerides of choline and of ethanolamine are also heavily labeled after a lag period; (5) in vivo labeling profiles resembled those obtained in vitro mainly regarding phosphatidylinositol biosynthesis; and (6) the presence of glycerol kinase in the CNS is suggested.