Biomedical subjects

B Michaud

Publications and source records attributed to B Michaud.

At least 19 recordsLinked to original sources

PubMed2000

Role of interleukin-1beta and tumour necrosis factor-alpha in lipopolysaccharide-induced sickness behaviour: a study with interleukin-1 type I receptor-deficient mice.

Interleukin-1 (IL-1) mediates symptoms of sickness during the host response to infection. IL-1 exerts its effects via several subtypes of receptors. To assess the role of IL-1 receptor type I (IL-1RI) in the sickness-inducing effects of IL-1, IL-1beta and the cytokine inducer lipopolysaccharide were administered to IL-1RI-deficient mice (IL-1RI-/-). Sickness was assessed by depression of social exploration, anorexia, immobility and body weight loss. IL-1RI-/- mice were resistant to the sickness-inducing effects of IL-1beta administered intraperitoneally (2 microg/mouse) and intracerebroventricularly (2 ng/mouse), but still fully responsive to lipopolysaccharide administered intraperitoneally (2.5 microg/mouse) and intracerebroventricularly (3 ng/mouse). The sensitivity of IL-1RI-/- mice to lipopolysaccharide was not due to a higher brain expression of proinflammatory cytokines other than IL-1, since lipopolysaccharide-induced expression of brain IL-1 beta, tumour necrosis factor-alpha (TNF-alpha) and IL-6 transcripts were identical in IL-1RI-/- and control mice when measured by semiquantitative reverse-transcriptase polymerase chain reaction 1 h after treatment. Blockade of TNF-alpha action in the brain by intracerebroventricular administration of a fragment of the soluble TNF receptor, TNF binding protein (3.6 microg/mouse), attenuated the depressive effects of intraperitoneal injection of lipopolysaccharide (1 microg/mouse) on behaviour in IL-1RI-/- but not in control mice. Since IL-1RI-/- mice were not more sensitive to intracerebroventricularly TNF-alpha (50 ng) than control mice, these results indicate that IL-1RI mediates the sickness effect of IL-1 and that TNF-alpha simply replaces IL-1 when this last cytokine is deficient.

Animals↗

PubMed1999

Increased sensitivity of prediabetic nonobese diabetic mouse to the behavioral effects of IL-1.

The nonobese diabetic (NOD) mouse is a model of spontaneous insulin-dependent diabetes mellitus (IDDM) or type I diabetes. In humans, and in animal models of IDDM, the progression of the disease is modulated by various environmental factors, particularly infectious agents. Interleukin-1 (IL-1) plays a pivotal role in the development of IDDM, and modulation of its synthesis may be a mechanism by which environmental modulation of disease progression occurs. Since various alterations at the level of the gene, number, and sensitivity of IL-1 receptors have been described in different animal models of autoimmune disease, we investigated, in the prediabetic NOD mouse, the presence of IL-1 receptors and their functional behavioral characteristics. Here we present evidence that prediabetic NOD mice exhibit a normal distribution and density of functional brain IL-1 receptors, but are more sensitive to the behavioral effects of IL-1 than the control ICR strain.

Animals↗

PubMed1999

Central injection of IL-10 antagonizes the behavioural effects of lipopolysaccharide in rats.

Peripheral (i.p.) and central (i.c.v.) injections of lipopolysaccharide (LPS) have been shown to induce brain expression of proinflammatory cytokines and to depress social behaviour in rats, increase duration of immobility and induce body weight loss. To determine if the anti-inflammatory cytokine, interleukin-10 (IL-10) is able to modulate these effects, recombinant rat IL-10 was injected in the lateral ventricle of the brain (30, 100, 300 ng/rat) prior to i.p. or i.c.v. injection of LPS (250 micrograms/kg or 60 ng/rat, respectively). Social exploration was depressed for 6 h after i.p. LPS injection. This effect was attenuated by IL-10 (30 and 100 ng) 2 h after injection, whereas the highest dose of IL-10 blocked the depression of social interaction for 6 h after LPS injection. IL-10 produced the same effects on the increase of immobility although the results did not reach significance. Social exploration was depressed 3 h after i.c.v. LPS injection, and this was accompanied by increased immobility. These effects were totally blocked by i.c.v. IL-10 (300 ng/rat). Rats lost body weight after i.c.v. LPS, and this effect was attenuated by i.c.v. IL-10. These results indicate that IL-10 is able to modulate the production and/or action of central proinflammatory cytokines.

Animals↗

PubMed1998

Interleukin-1-induced sickness behavior depends on behavioral lateralization in mice.

Inter-individual differences in brain-immune interactions have been demonstrated previously in mice using lateralization as a behavioral trait of population heterogeneity. Lipopolysaccharide (LPS), which is known to induce neurochemical, neuroendocrine, and immune responses depending on lateralization, is also able to induce sickness behavior, via the production of interleukin-1 (IL-1). The objective of this study was to determine whether lateralization can influence the behavioral response to LPS and to IL-1. To test this hypothesis, adult female C3H mice, previously selected for paw preference in a food reaching task, were injected intraperitoneally (i.p.) with 0.75 microg LPS or 0.75 microg recombinant IL-1beta. Sickness induced by these molecules was measured by depressed social behavior, increased immobility, loss of body weight, and reduced food intake during the 6 h following injection. LPS-induced sickness was similar in right- and left-pawed mice. In contrast, IL-1-induced sickness behavior was dependent on behavioral lateralization. IL-1-induced depression of social investigation was more pronounced in right-pawed mice than in left-pawed animals. Likewise, IL-1-induced immobility was more important in right-pawed mice. There was a similar trend for food intake to be lower and loss of body weight to be higher in right-pawed mice than in left-pawed animals. These results demonstrate that right-pawed mice are more sensitive to IL-1-induced sickness than left-pawed animals. They extend our previous data showing a greater susceptibility to stress of right-pawed animals. The existence of inter-individual differences in the reactivity to stress or immune activation may be useful to study the mechanisms of the various strategies used by an individual in response to environmental aggressions.

Animals↗

PubMed1998

Biological activity and brain actions of recombinant rat interleukin-1alpha and interleukin-1beta.

IL-1alpha and IL-1beta have potent effects on the central nervous system resulting in fever, activation of the hypothalamic-pituitary-adrenal axis and behavioural depression. These effects have mainly been studied in rats, using recombinant human and mouse IL-1. Because IL-1alpha and IL-1beta show some species specificity in the potency of their biological activities, the objective of the present work was to directly compare the effects of recombinant rat IL-1alpha and IL-1beta in the rat system as a first step to dissect out the mechanisms that are involved in these effects. In vitro, recombinant rat IL-1alpha and IL-1beta bound with the same affinity as human IL-1 to the rat insulinoma Rin m5F cell line that mainly expresses type I IL-1 receptors. This binding activated IL-1 receptors, as shown by induction of the synthesis of TNF-alpha mRNA. In vivo, recombinant rat IL-1alpha and IL-1beta enhanced body temperature, increased plasma levels of corticosterone and ACTH, and depressed social behaviour. All these effects were obtained at doses 100-1,000 fold lower when IL-1 was injected centrally than when it was administered peripherally, indicating that they are centrally mediated. The relative potencies of recombinant rat IL-1alpha and IL-1beta were not the same depending on the endpoint and the route of injection, indicating that different mechanisms are likely to be involved in the various effects of IL-1 on the brain.

Animals↗

PubMed1997

Hypersensitivity of lurcher mutant mice to the depressing effects of lipopolysaccharide and interleukin-1 on behaviour.

Lurcher mutant mice are characterized by a fast and almost total loss of olivocerebellar neurones during the first postnatal month, associated with a chronic inflammatory state. To test their brain sensitivity to proinflammatory cytokines, we assessed the behavioural responses of adult male Lurcher and wild type to an i.p. or i.c.v. injection of rat recombinant IL-1 beta, and lipopolysaccharide (LPS). IL-1 beta (15 micrograms kg-1, i.p. or 1 ng i.c.v.) decreased social exploration measured 2, 4 and 6 h later, and this decrease was significantly more pronounced in Lurcher than in wild type mice. LPS (60 micrograms kg-1, i.p. or 5 ng i.c.v.) decreased social exploration measured 2 and 4 h later, and this effect was also significantly more marked in Lurcher than in wild type mice. These results suggest that the chronic inflammatory state which characterizes Lurcher mice renders these animals more sensitive to the effects of cytokines such as IL-1 beta and LPS. This difference may be due to the higher reactivity of brain macrophages and glial cells to LPS and IL-1 in Lurcher mice than in wild type.

Animals↗

PubMed1997

Cholecystokinin receptors do not mediate the behavioral effects of lipopolysaccharide in mice.

To test the possible role of cholecystokinin (CCK) in the decrease of social exploration induced by intraperitoneal (IP) injection of lipopolysaccharide (LPS, 100 microg/kg), mice were pretreated with IP or intracerebroventricular (ICV) injection of the CCKA receptor antagonist L-364,718 (3 mg/kg and 10 microg/kg, respectively) and the CCKB receptor antagonist L-365,260 (1 mg/kg and 10 microg/kg, respectively). L-364,718 and L-365,260 did not alter LPS-induced decrease in social investigation, whatever the route of administration, suggesting that endogenous cholecystokinin does not mediate the effect of proinflammatory cytokines on social exploration in mice.

Animals↗

PubMed1997

Efficient in vivo delivery of DNA to pulmonary cells using the novel lipid EDMPC.

We compared the efficacy of gene transfer in vitro and in vivo using various formulations of DNA-lipid complexes based on the novel cationic lipid EDMPC (1,2-dimyristoylsn-glycero-3-ethylphosphocholine, chloride salt). In vitro studies analyzed delivery of marker genes to four established cell lines, including two of pulmonary origin. The in vivo analysis used intralobar delivery of marker genes and CFTR to mice and rats. We observed a lack of positive correlation between those DNA-EDMPC formulations that delivered DNA most efficiently in vitro and those that worked best in vivo. Intralobar DNA delivery to rodents mediated by EDMPC was efficient. The high level of gene delivery by DNA-EDMPC formulations demonstrates that efficient lipid-mediated gene transfer to the lung is possible.

Animals↗

PubMed1996

Vagotomy blocks behavioural effects of interleukin-1 injected via the intraperitoneal route but not via other systemic routes.

To test specificity of the involvement of vagal afferents in the communication between the immune system and the brain, sham-operated and vagotomized mice were injected i.p., s.c. or i.v. with physiological saline or interleukin-1 beta (IL-1 beta [symbol: see text] 4 weeks after surgery. Vagotomy attenuated the decrease in social exploration induced by i.p. injection of 300 ng recombinant human IL-1 beta but had no effect when IL-1 beta was injected s.c. (300 ng) or i.v. (500 ng). Vagotomy also attenuated the depression in social investigation induced by i.p. injection of recombinant rat IL-1 beta (IL-1 beta, 1 microgram) but was without effect when 1 microgram IL-1 beta was injected i.v. These results confirm the role of vagal afferent nerves in the transmission of an immune message from the periphery to the brain and show that the vagus nerve only conveys information concerning cytokines injected into the abdominal cavity.

Animals↗

PubMed1996

Vagotomy attenuates behavioural effects of interleukin-1 injected peripherally but not centrally.

Peripheral and central injections of recombinant rat interleukin-1 beta (IL-1 beta) have been shown to decrease social exploration in rats. To test the involvement of vagal afferents in the communication between the immune system and the brain, sham-operated and vagotomized rats were injected peripherally or centrally with physiological saline or IL-1 beta 4 weeks after surgery. Vagotomy attenuated the depression in social exploration induced by i.p. administration of IL-1 beta (15 micrograms) but did not alter the behaviour-depressing effects of an intracerebroventricular (i.c.v.) injection of IL-1 beta (45 ng). These results confirm the role of vagal afferent nerves in the transmission of an immune message from the periphery to the brain, and show that vagotomy does not impair the direct sensitivity of the brain itself to immune signals.

Analysis of Variance↗

PubMed1988

Influence of stressor predictability and behavioral control on lymphocyte reactivity, antibody responses and neuroendocrine activation in rats.

The present experiments were designed to study the influence of prediction and control of electric shocks on various aspects of immune function, and the possible intermediate role of glucocorticoid hormones. After two sessions of inescapable footshocks, the reactivity of splenocytes to concanavalin A was reduced by one third. This effect was completely reversed when each shock was preceded by a warning stimulus, even though the adrenocortical response was the same in both conditions. In another experiment, rats were submitted to ten sessions of continuous avoidance in a shuttle-box and a group of yoked animals received the same footshocks without any relationship to their shuttling behavior. Although yoked rats displayed a reduced reactivity of splenocytes to lectins, animals of the avoidance group had a reduced antibody response to sheep erythrocytes. In contrast, no difference was observed in the corticosterone or prolactin response. These data further support the importance of psychological factors on stress-induced changes in immune functions. Furthermore, they demonstrate that various aspects of the immune system are differentially affected by behavioral factors and the results argue against a major role for the adrenocortical system in mediating these changes.

Adaptation, Psychological↗

PubMed1987

Centrally injected arginine vasopressin (AVP) facilitates social memory in rats.

'Memory' for a juvenile conspecific in male rats can be measured by variation in duration of investigation times when the same juvenile is presented at different intervals. Typically, exposure of an adult male rat to a juvenile results in transient investigatory activity that rapidly declines with repeated exposures at short interexposure intervals (30 min). Longer interexposure intervals (120 min) result in re-investigation with durations similar or greater than the original investigation. Arginine vasopressin (AVP) injected into adult male rats intracerebroventricularly in doses of 0.5-2.0 ng immediately after investigation of the juvenile decreased social investigation of the same juvenile at the long (120 min) interexposure interval. This decrease in investigatory time was similar to that observed after a 30-min interexposure interval in untreated animals. These results support the hypothesis that increasing the availability of AVP in the central nervous system can improve the consolidation of olfactory information and improve conspecific recognition in rats.

Animals↗

PubMed1986

Behavioural, physiological and immunological consequences of social status and aggression in chronically coexisting resident-intruder dyads of male rats.

The behavioural and physiological consequences of social status and reciprocal fighting in resident-intruder dyads of Long Evans male rats were evaluated. Before a chronic cohabitation of 10 days, residents and intruders were individually housed for one month to increase their aggressiveness. Control animals included isolates, i.e., animals kept individually housed throughout the experiment and pair-housed rats, i.e., pairs of rats housed together from their rats in the laboratory. In 19 out of 20 dyads, a clear dominance relationship developed with an advantage to the resident in 68% of the cases. Dominants showed more exploratory activity than subordinates in a open-field test at the end of the cohabitation period; subordinates groomed longer than animals from other experimental groups. Dominants had lower pain thresholds than individually and pair-housed animals. Both dominants and subordinates had higher tyrosine hydroxylase enzymatic activities in the left adrenal than isolated and pair-housed rats. Subordinates lost body weight and had higher plasma corticosteroid concentrations than animals from the other experimental groups. In addition, they had smaller thymus glands and reduced spleen lymphocyte responses to mitogenic stimulation in vitro, in comparison to dominant animals. These results show that subordination in the dyadic resident-intruder paradigm leads to a complex syndrome of behavioural and physiological changes, some of which may be modulated by the intensity of aggressive interactions.

Adrenal Glands↗

PubMed1985

[The anterior and transperitoneal approach in the surgery of the kidney and ureter].

Because of the variety of situations encountered in surgery of the kidney and ureter, the methods of approach to these organs need to be diversified. In this context, the authors discuss the place of the anterior and transperitoneal approach, based on a series of 573 cases. Its principal indications are: excision of large kidney tumours or pseudo-tumours, conservative treatment of hydronephrosis, removal of pelvic calculi, staged operations or operations on bilateral lesions, re-operations resulting in secondary nephrectomy or repair of the collecting system. The modalities, advantages and disadvantages are discussed and the authors stress the complications which may result from opening of the peritoneum. Overall, the anterior and transperitoneal approach, in the situations in which it is indicated, is an easy and safe operative technique, superior to the usual sub-peritoneal approaches. Its results are very satisfactory; they should overcome reservations which have surrounded this technique for so long and should give it a definite place beside the classical approaches, which nevertheless remain supreme.

Abdomen↗

PubMed1979