Biomedical subjects

J M Bourre

Publications and source records attributed to J M Bourre.

At least 19 recordsLinked to original sources

PubMed2002

Docosahexaenoic acid-rich phospholipid supplementation: effect on behavior, learning ability, and retinal function in control and n-3 polyunsaturated fatty acid deficient old mice.

This study investigated the effects of docosahexaenoic acid (DHA)-rich phospholipid supplementation on behavior, electroretinogram and phospholipid fatty acid (PUFA) composition in selected brain regions and retina in old mice. Two groups of mice were fed a semisynthetic balanced diet or a diet deficient in alpha-linolenic acid. At the age of 8 months, half of each diet group was supplemented with DHA. In the open field, no differences in motor or exploratory activities were observed between the four diet groups. In the light/dark test of anxiety, the time spent in the light compartment was significantly higher in both supplemented groups than in control and deficient groups. Learning performance in the Morris water maze was significantly impaired in deficient old mice, but was completely restored by the phospholipid supplementation. The electroretinogram showed a significant alteration of a- and b-wave amplitudes in control compared to deficient mice. Phospholipid supplementation induced a significant increase of b-wave amplitude in both control and deficient groups and restored normal fatty acid composition in brain regions and retina in deficient mice. DHA-rich phospholipids may improve learning ability, visual function and reverse biochemical modifications in old mice fed an n-3 polyunsaturated fatty acid-deficient diet; they also may improve visual function in old mice fed a balanced diet.

Animals↗

PubMed2001

Learning and latent inhibition in old mice.

The inhibitory component of selective attention has been compared in young (7-8 weeks) and older (9-10 months) female mice using the latent inhibition (LI) paradigm. LI consists of retardation in conditioning to a stimulus as a consequence of its prior non-reinforced pre-exposure. In the present work, active avoidance of an electric footshock signaled with a sound was used. Avoidances of the electric footshocks were significantly reduced in old relative to young mice which did not differ regarding pain threshold. This likely results from a slower learning in old mice. LI was significantly present and of the same importance in both young (46%) and old (49%) mice. These results suggest that in 8-9 months-old mice, the learning ability is reduced but the inhibitory component of selective attention is not altered.

Acoustic Stimulation↗

PubMed2000

Nutritional (n-3) polyunsaturated fatty acids influence the behavioral responses to positive events in mice.

The effect of (n-3) polyunsaturated fatty acid (PUFA) diet deficiency on behavioural responses to appetitive events was assessed in OF1 mice. Pups fed the same diet (deficient in alpha-linolenic acid or a standard control diet) as their dams were used aged 7 to 11 weeks. In a free choice model, the preference for a sucrose solution in both males and females was significantly lower in deficient than in control mice. Morphine conditioned place preference was obtained with the two diets at 8 and 16 mg/kg morphine, but the lower dose of 4 mg/kg induced a place preference in control but not in (n-3) deficient mice. Taken together, these results suggest that a nutritional (n-3) PUFA deficiency can alter the responsiveness to appetitive events.

Animals↗

PubMed2000

Morphine-induced sensitization of locomotor activity in mice: effect of social isolation on plasma corticosterone levels.

This study examined the influence of social isolation on behavioural sensitization to the locomotor effect of morphine and the link between this behaviour and plasma corticosterone concentrations. Four weeks isolation induced an increase in the locomotor effect of morphine. In social and isolated mice, repeated administrations (6) of morphine (one injection every 3 or 4 days) followed by 3 h in an actimeter induced behavioural sensitization to the locomotor effect of morphine. No interaction was observed between social isolation and behavioural sensitization to morphine. Resocializing previously isolated mice for 3 weeks reduced the morphine-induced locomotor effect without altering the behavioural sensitization. Corticosterone plasma levels were more increased (416%) in mice isolated 5 weeks than in mice isolated for 2 weeks (243%) and they return to the control levels following 3 weeks of resocialization. Since there was no interaction between the increase in morphine locomotor effect induced by social isolation and the morphine-induced behavioural sensitization, it is suggested that each of these two events acts independently. Whether or not a common mechanism (plasma corticosterone levels?) partly underlies both effects, the result resembles a simple additive effect.

Adrenal Cortex↗

PubMed2000

Specific phospholipid fatty acid composition of brain regions in mice. Effects of n-3 polyunsaturated fatty acid deficiency and phospholipid supplementation.

This study examined the effects of dietary alpha-linolenic acid deficiency followed or not by supplementation with phospholipids rich in n;-3 polyunsaturated fatty acid (PUFA) on the fatty acid composition of total phospholipids in 11 brain regions. Three weeks before mating, mice were fed a semisynthetic diet containing both linoleic and alpha-linolenic acid or deficient in alpha-linolenic acid. Pups were fed the same diet as their dams. At the age of 7 weeks, a part of the deficient group were supplemented with n;-3 polyunsaturated fatty acids (PUFA) from either egg yolk or pig brain phospholipids for 2 months. Saturated and monounsaturated fatty acid levels varied among brain regions and were not significantly affected by the diet. In control mice, the level of 22:6 n-3 was significantly higher in the frontal cortex compared to all regions. alpha-Linolenic acid deficiency decreased the level of 22:6 n-3 and was compensated by an increase in 22:5 n-6 in all regions. However, the brain regions were affected differently. After the pituitary gland, the frontal cortex, and the striatum were the most markedly affected with 40% reduction of 22:6 n-3. Supplementation with egg yolk or cerebral phospholipids in deficient mice restored a normal fatty acid composition in brain regions except for the frontal cortex. There was a regional distribution of the fatty acids in the brain and the impact of deficiency in alpha-linolenic acid was region-specific. Dietary egg yolk or cerebral phospholipids are an effective source of n-3 PUFA for the recovery of altered fatty acid composition induced by a diet deficient in n-3 PUFA.

Animals↗

PubMed2000

Phospholipid supplementation reverses behavioral and biochemical alterations induced by n-3 polyunsaturated fatty acid deficiency in mice.

This study investigated the effects of a diet deficient in alpha-linolenic acid followed or not by supplementation with phospholipids rich in n-3 polyunsaturated fatty acids (PUFA) on behavior and phospholipid fatty acid composition in selected brain regions. Three weeks before mating, two groups of mice were fed a semisynthetic diet containing both linoleic and alpha-linolenic acid or a diet deficient in alpha-linolenic acid. Pups were fed the same diet as their dams. At the age of 7 weeks, a part of the deficient group was supplemented with n-3 PUFA from either egg yolk or pig brain phospholipids for 2 months. In the open field, rearing activity was significantly reduced in the deficient group. In the elevated plus maze (anxiety protocol), the time spent on open arms was significantly smaller in deficient mice than in controls. Using the learning protocol with the same task, the alpha-linolenic acid deficiency induced a learning deficit. Rearing activity and learning deficits were completely restored by supplementation with egg yolk or cerebral phospholipids, though the level of anxiety remained significantly higher than that of controls. There were no differences among the 4 diet groups for either the Morris water maze or passive avoidance. In control mice, the level of 22:6 n-3 was significantly higher in the frontal cortex compared to all other regions analysed. The frontal cortex and the striatum were the most markedly affected by the deficiency. Supplementation with phospholipids restored normal fatty acid composition in brain regions except for frontal cortex. Egg yolk or cerebral phospholipids are an effective source of n-3 PUFA for reversing behavioral changes and altered fatty acid composition induced by a diet deficient in n-3 PUFA.

Animals↗

PubMed2000

Diets containing long-chain n-3 polyunsaturated fatty acids affect behaviour differently during development than ageing in mice.

The effect of a standard diet providing essential fatty acids enriched in fish oil or palm oil was studied in young, mature and old mice. Two groups of pregnant and lactating OF1 mice were fed on diets with or without high levels of long-chain n-3 polyunsaturated fatty acids. Offspring were maintained on these diets after weaning. The litter size did not differ. The weight increased more quickly in fish-oil-fed mice than palm-oil-fed mice. The fish-oil diet induced a significant increase in exploratory activity in young mice which was not found in mature and old mice. The level of locomotor activity was significantly higher in young, no different in mature, and lower in old fish-oil-fed mice than in controls. Habituation, the simpler form of learning, occurred to the same extent in the two diet groups. For the place learning protocol of the Morris water maze there was no difference between the two diet groups; however, in the probe trial, the mature fish-oil-fed mice remembered the situation well compared with the control mice. In the active avoidance test, on the first day of acquisition the young fish-oil-fed mice made more avoidances than control mice, whereas in contrast, mature and old-fish-fed mice made less avoidances than control mice. These results suggest a positive effect on arousal and learning ability of a diet enriched in long chain n-3 polyunsaturated fatty acids in young mice and a detrimental effect in old mice.

Aging↗

PubMed1999

Learning deficits in first generation OF1 mice deficient in (n-3) polyunsaturated fatty acids do not result from visual alteration.

The effects of (n-3) polyunsaturated fatty acids (PUFA) diet deficiency on learning, electroretinogram and retinal fatty acid composition were assessed for the first time in OF1 mice. Pups fed the same diets (deficient in alpha-linolenic acid or a control) as their dams were used aged 7 weeks for passive avoidance test and fatty acid analysis of retinal phospholipids. Visual function was measured by electroretinography in 4- and 7-week-old mice. The (n-3) PUFA-deficient diet significantly decreased learning performance and retinal docosahexaenoic acid level in adult mice. The electroretinogram showed a significant alteration of b-wave amplitude in deficient mice at 4 weeks but not at 7 weeks. These results show that learning deficits in mice fed a diet deficient in (n-3) PUFA were not due to visual alteration.

Animals↗

PubMed1999

Effect of social isolation on the metabolism of morphine and its passage through the blood-brain barrier and on consumption of sucrose solutions.

RATIONALE: We have previously shown that place preference conditioning to morphine was observed in social mice at the dose of 8 mg/kg, whereas 4 weeks of isolation impairs the place preference conditioning to morphine (8-100 mg/kg). OBJECTIVE: The present study, aimed at explaining this phenomenon, tested three hypotheses: firstly, a reduced sensitivity to reinforcers induced by isolation; secondly, a difference in morphine disposition in isolated and social mice; thirdly, an altered blood-brain barrier transport of morphine in isolated mice. METHODS: In the sucrose experiments, mice had the choice (for 24 h) between a bottle containing tap water and a bottle containing a sucrose solution. Three sucrose concentrations were used: 0.5, 1 and 2% (weight/weight). In the morphine disposition experiments, the plasma levels of morphine and of morphine-3-glucuronide (M3G) were measured for 240 min. The brain concentrations of morphine was measured at 15 and 30 min. The passage of morphine through the blood-brain barrier was measured using a method modified from that of Takasato (1984). RESULTS: The preference for the sucrose solutions was significantly greater in isolated than in social mice for the concentration of 2%. Isolation reduced the plasma levels of morphine and of M3G, but did not alter the brain concentration of morphine. The passage of morphine through the blood-brain barrier was altered by isolation in neither of the eight structures examined. CONCLUSIONS: We conclude that the behavioural effect of isolation observed in the conditioned place preference to morphine may depend on changes both in morphine disposition and in the sensitivity to reinforcers in isolated mice.

Analgesics, Opioid↗

PubMed1999

Age-induced cognitive alterations in OF1 mice.

Female OF1 mice aged 17-18 months were compared with female OF1 mice aged 7-11 weeks for locomotor activity, pain sensitivity, and cognitive performance using the Morris water maze, passive and active avoidance, and the elevated plus-maze learning protocol. Performance of old mice was impaired compared to those of young mice for both locomotor activity, pain sensitivity, and the four cognitive tests including the elevated plus-maze not previously used in studies on aging. Using complementary experiments and a detailed analysis of the results, we have shown that the reduction of learning and memory do not result from a decline of sensory and motor capacities. We conclude that female OF1 mice aged 17-18 months show true cognitive deficits.

Aging↗

PubMed1999

Dexamethasone regulation of P-glycoprotein activity in an immortalized rat brain endothelial cell line, GPNT.

The blood-brain barrier (BBB) plays an important role in controlling the passage of molecules from the blood to the extracellular fluid environment of the brain. The multidrug efflux pump P-glycoprotein (P-gp) is highly expressed in the luminal membrane of brain capillary endothelial cells, thus forming a functional barrier to lipid-soluble drugs, notably, antitumor agents. It is of interest to develop an in vitro BBB model that stably expresses P-gp to investigate the mechanisms of regulation in expression and activity. The rat brain endothelial cell line, GPNT, was derived from a previously characterized rat brain endothelial cell line. A strong expression of P-gp was found in GPNT monocultures, whereas the multidrug resistance-associated pump Mrp1 was not expressed. The transendothelial permeability coefficient of the P-gp substrate vincristine across GPNT monolayers was close to the permeability coefficient of bovine brain endothelial cells cocultured with astrocytes, a previously documented in vitro BBB model. Furthermore, the P-gp blocker cyclosporin A induced a large increase in apical to basal permeability of vincristine. Thus, P-gp is highly functional in GPNT cells. A 1-h treatment of GPNT cells with dexamethasone resulted in decreased uptake of vincristine without any increase in P-gp expression. This effect could be mimicked by protein kinase C (PKC) activation and prevented by PKC inhibition, strongly suggesting that activation of P-gp function may involve a PKC-dependent pathway. These results document the GPNT cell line as a valuable in vitro model for studying drug transport and P-gp function at the BBB and suggest that activation of P-gp activity at the BBB might be considered in chemotherapeutic treatment of cancer patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

The role of peroxisomes in aging.

Reactive oxygen species and alterations in membrane lipid homeostasis are thought to be important events in aging process and aging-related degenerative diseases. The peroxisome is a small cellular organelle involved in both oxygen and lipid metabolism, and defects in peroxisomal function are associated with major, and often fatal, changes at the neurological level during human development. Recent reports of aging-related changes in peroxisomal function raised the hypothesis that peroxisomes may also have a significant role in the aging process and aging-related degenerative diseases. This review presents the current data on changes in peroxisomal function during aging and discusses the implications of these changes for health.

Aging↗

PubMed1997

Graded dietary levels of RRR-gamma-tocopherol induce a marked increase in the concentrations of alpha- and gamma-tocopherol in nervous tissues, heart, liver and muscle of vitamin-E-deficient rats.

The effect of dietary RRR-gamma-tocopherol supplementation on serum and tissue alpha- and gamma-tocopherol concentrations was studied in vitamin-E-deficient rats fed diets containing adequate levels of RRR-alpha-tocopherol and graded levels of RRR-gamma-tocopherol over a 60 day period. Feeding rats with a RRR-alpha-tocopherol-supplemented diet induced in forebrain, sciatic endoneurium, skeletal muscle, heart and liver a marked increase in alpha-tocopherol concentration. In contrast, feeding rats with a diet containing the same level of RRR-gamma-tocopherol induced a small increase in gamma-tocopherol concentrations in brain, sciatic endoneurium, skeletal, muscle, heart and liver and a slight but significant decrease in alpha-tocopherol concentration in all tissues examined. In rats fed diets containing a constant level of RRR-alpha-tocopherol and graded levels of RRR-gamma-tocopherol, the concentrations of alpha-tocopherol in all tissues were much higher than those in rats fed a control diet containing RRR-alpha-tocopherol alone. The higher the gamma/alpha ratio, the more the alpha-tocopherol concentrations increased. Significant positive linear regressions were found between the gamma/alpha ratio and the alpha- and gamma-tocopherol concentrations in most of the tissues examined. These results indicate that when gamma-tocopherol was supplied continuously in the diet gamma-tocopherol accumulated significantly in the tissues but to a much smaller extent than when rats were fed with RRR-alpha-tocopherol. These experiments also indicate that gamma-tocopherol did not depress the serum and tissue alpha-tocopherol concentrations. On the contrary, gamma-tocopherol supplements induced a marked increase in alpha-tocopherol concentrations in the serum and tissues. These results suggest that there is a relationship between alpha- and gamma-tocopherol levels in vivo and that the biopotency of alpha-tocopherol should be reevaluated especially when high levels of gamma-tocopherol were present in the diet.

Animals↗

PubMed1997

Possible role of the choroid plexus in the supply of brain tissue with polyunsaturated fatty acids.

Delta-6 desaturase was measured in rat brain microvessels and choroid plexus by incubation in the presence of radioactive linoleic acid. Under our conditions, in 21-day-old animals, delta-6 desaturase was not detected in brain microvessels. In contrast, it was present in choroid plexus (about 21 pmol/min per mg protein). In comparison, the activity in brain was much lower (about 1 pmol/min per mg protein) and higher in liver (about 55 pmol/min per mg protein). Interestingly, during development the activity in choroid plexus peaked at day 6 after birth and declined slightly thereafter. The pattern of incorporation of linoleic acid radioactivity was not the same in choroid plexus and microvessels. These results show that delta-6 desaturase was not detected in brain microvessels but was present in choroid plexus.

Aging↗

PubMed1997

Isolation impairs place preference conditioning to morphine but not aversive learning in mice.

Morphine (8-100 mg/kg IP) induces place preference conditioning in mice. The effect of two different periods of isolation (15 and 30 days) was examined. Mice isolated for 15 days but not 30 days exhibited place preference conditioning to morphine (8 mg/kg). After 30 days of isolation morphine could not induce place preference conditioning with the following doses (8, 16, 64, 100 mg/kg). Social regrouping of male mice previously isolated for 30 days with naive female mice for 15 or 30 days resulted in a reappearance of the conditioned place preference to morphine (16 mg/kg). The specificity of this associative deficit was examined by testing learning in isolated compared to non-isolated mice in two distinct settings: escape learning in the Morris water maze and passive avoidance acquisition and retention. On the Morris water maze isolated mice did not differ from non-isolated mice regarding place learning, the probe trial or extinction. Isolated mice were unimpaired in passive avoidance acquisition and retention. It was concluded that the deficits in place preference conditioning were not the result of a global learning impairment in isolated mice.

Analgesics, Opioid↗

PubMed1997

Effect of isolation on pain threshold and on different effects of morphine.

1. The effect of three periods of isolation (8, 15 and 30 days) were studied in mice on the pain threshold and the sensitivity to morphine. 2. The pain threshold was unchanged after 8 and 15 days of isolation but increased after 30 days of isolation. 3. The analgesic effect of morphine was unchanged after 8 and 15 days of isolation but increased after 30 days of isolation. 4. The tolerance to morphine analgesia was unchanged after 8 and 15 days of isolation but increased after 30 days of isolation (morphine-induced analgesia was reduced). 5. The physical dependence on morphine induced by precipitated withdrawal was unchanged after 8 and 15 days of isolation but decreased after 30 days of isolation. 6. It is suggested that isolation may modify the metabolism the metabolism/absorption of morphine in a different way according as the treatment is unique or chronic.

Analgesia↗

PubMed1997

Alterations in eighteen-carbon saturated, monounsaturated and polyunsaturated fatty acid peroxisomal oxidation in mouse brain during development and aging.

Peroxisomal oxidation was measured in mouse brain homogenate by adding cyanide to the test tube (which inhibits mitochondrial oxidation). Eighteen-carbon fatty acids (saturated, monounsaturated and polyunsaturated) were oxidized by brain peroxisomes. At nearly all ages, oxidation of oleic acid was higher (about 2 fold) than oxidation of other eighteen-carbon fatty acids. In contrast to other fatty acids, stearic acid oxidation decreased regularly up to weaning (6 fold) and was stable thereafter. Oleic acid oxidation increased up to weaning, decreased during development up to day 70 and remained subsequently nearly stable. Linoleic acid and alpha-linolenic acid oxidation increased up to weaning, decreased up to day 105 and was nearly stable thereafter. Alpha-linolenic acid oxidation about was two fold lower than linoleic acid oxidation. Interestingly, peroxisomal oxidation for all fatty acids examined declined during aging, between day 365 and day 450.

Aging↗

PubMed1997

Endogenous synthesis cannot compensate for absence of dietary oleic acid in rats.

It is important to know whether an organism is able to synthesize all the oleic acid it needs. To determine this, it is sufficient to feed animals a diet containing essential fatty acids but totally lacking oleic acid, and then determine whether tissue concentrations of fatty acids of the (n-9) series are altered due to insufficient endogenous synthesis of oleic acid from stearic acid. In fact, the effects of a total oleic acid deficiency have not previously been studied because all the vegetable oils used in human and animal nutrition contain this fatty acid in variable amounts. Thus, we fed rats semipurified diets whose lipids (triglycerides) were synthesized chemically. Female rats were fed the diets for 3 wk before mating, and their pups (fed the same diets) were killed when 21 and 60 d old. Generally speaking, oleic acid deficiency resulted in a lower level of this acid in the various organs examined (liver, kidney, testes, heart, muscle and sciatic nerve in 21-d-old rats and liver, kidney, heart, muscle and sciatic nerve in 60-d-old rats). Brain, myelin and nerve endings were not affected at either age. This lower level was accompanied by a higher level of 16:1(n-7) and, to a lesser extent, 18:1(n-7). Dietary supplementation with oleic acid (1666 mg/100 g diet) for up to 21 d resulted in normal levels of this fatty acid in some organs (liver, heart, sciatic nerve) but not in others (kidney, muscle, testes) and a decrease in 16:1(n-7), which returned to about the same levels as in the control group in all organs except liver. Adding small or large amounts of stearic acid to the oleic acid-deficient diet had little or no effect on oleic acid levels in the tissues. We conclude that rats (particularly in liver) do not have sufficient synthesizing potential to guarantee the normal fatty acid composition of certain organs if oleic acid is totally absent in the diet.

Animals↗