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Biomedical subjects

P J Neveu

Publications and source records attributed to P J Neveu.

At least 19 recordsLinked to original sources

Activity of the hypothalamic-pituitary-adrenal axis in mice selected for left- or right-handedness.

Asymmetry in brain modulation of the immune system has been previously described. In mice, paw preference has been shown to be associated with immune reactivity but the mechanisms involved in such an association are not yet known. The autonomic nervous system and the neuroendocrine system are considered as major candidates for neural influences on the immune system. In the present study, the activity of the hypothalamic-pituitary-adrenal (HPA) axis of adult female mice selected for paw preference (left-handers vs. right-handers) was assessed by measuring both adrenocorticotropic hormone (ACTH) and corticosterone plasma levels, as well as the in vitro responses of hypothalamus and adrenocortical cells to various hormone releasing stimuli. The results reported here showed no difference in the activity of the HPA axis between left- and right-handed mice, suggesting that this neuroendocrine axis is not implicated in the association between functional brain asymmetry and immune reactivity. However, our results do not exclude the possibility that the HPA axis could play a role in such an association under other circumstances, such as during development or stressful situations.

Adrenocorticotropic Hormone

Early effects of unilateral lesions of substantia nigra on immune reactivity.

It has recently been demonstrated that central dopaminergic pathways are asymmetrically involved in the modulation of the immune response. Mitogen-induced proliferation of T lymphocytes was shown to be enhanced 4-6 weeks after right lesion of the substantia nigra (SN) in mice, when compared to left lesioned and control animals. In order to study the involvement of post lesion neuronal reorganization in these results, the same immunological parameters were determined as early as 2 weeks after right or left lesion of the SN. We showed that the lymphoproliferation induced by alpha CD3 and concanavalin A was decreased in both lesioned groups, but phytohemagglutinin-induced mitogenesis was more impaired in the right than in the left lesioned animals. Hence, the time course effects of the right lesions of SN shifted from depression to enhancement of the T lymphocyte responsiveness. This shift appeared to occur around the two weeks period following the lesion. These immunomodulatory effects of unilateral SN lesioning, which depended on time and side of lesion, were similar to those observed after hemidecortication. Based on these findings, it is reasonable to suggest that asymmetry in brain immunomodulation involves functionally related dopaminergic and cortical networks.

Animals

Asymmetrical brain modulation of immune reactivity in mice: a model for studying interindividual differences and physiological population heterogeneity?

Functional brain asymmetry is associated with immune reactivity in mice. This association depends on the immunological parameters tested and on the sex and genetic background of animals. Each individual may be characterized by a paw preference score in relation with a particular immune pattern. The interindividual differences in immune reactivity connected with brain asymmetry give a new insight in the relation brain immunity and may represent a new aspect of population polymorphism.

Animals

Embedded adrenal cells graft reduced local and early nonspecific inflammatory phenomena which follow agarose beads implantation.

Microencapsulation of adrenal cells is proposed for reducing the nonspecific inflammatory reaction observed around polymer implants. This hypothesis was tested by comparing both host cellular reaction and the surrounding graft cell populations which appeared either when agarose embedded cells or when empty agarose beads were implanted. Our results showed that the fibrotic material that surrounded the implanted empty agarose microbeads was not as severe and important when adrenal cells were present. Similarly, T lymphocyte population surrounding the graft was considerably reduced together with the percentage of CD4 and CD8 positive cell subpopulations. The activation macrophage marker IaD disappeared. Our results support the hypothesis that embedded adrenal cells may be a suitable solution for reducing early inflammatory events due to microcapsules implantation.

Adrenal Cortex

Strain and sex differences in the degree of paw preference in mice.

The direction and degree of paw preference was studied in male and female mice from the C3H/He, C3H/OuJIco and New Zealand Black (NZB) strains, using the method previously described by Collins. All the populations of mice tested exhibited a low degree of lateralization, which varied among strains: NZB mice were more strongly lateralized than both C3H substrains; C3H/He had a higher degree of lateralization than C3H/OuJIco mice. Females tended to be more strongly lateralized than males, particularly in the C3H/He mice. No direction bias was observed in the strains tested, as lateralized mice were equally distributed into left-and right-handers. The distributions of paw preference found in the strains tested in this study are different from those obtained by Collins in C57BL/6J mice, in that most of his animals were strongly lateralized and only a few were ambidextrous. These strain differences in the degree of paw preference may be explained by genetic factors or differential rearing histories, which are known to influence the development of brain asymmetries.

Animals

Sex-dependent association between immune function and paw preference in two substrains of C3H mice.

Asymmetry in brain modulation of the immune system has been previously described in mice. Paw preference is known to be associated with immune reactivity but the respective roles of sex and genetic background in this association remain to be elucidated. In this work, male and female mice of the C3H/He and C3H/OuJIco substrains were selected as right- and left-handers. Mitogen-induced lymphoproliferation and natural killer cell activity were then tested. Left-handed female mice of both C3H substrains exhibited higher mitogenesis than right-handers but no association between paw preference and NK cell activity was found in females. Conversely, in males of both substrains, right-handers showed enhanced NK cell activity compared to left-handers but no association between paw preference and mitogenesis was observed in males. Only small differences in the strength, but not in the direction, of the association between paw preference and immune functions were observed between the two C3H substrains. These results show that the association between paw preference and immune reactivity in mice varies according to the immune parameters tested and is a sex-dependent phenomenon in which the genetic background may be involved.

Animals

Functional brain asymmetry and lymphocyte proliferation in female mice: effects of right and left cortical ablation.

Brain immunomodulation may be lateralized as evidenced by two experimental approaches. Using a behavioral paradigm, we have reported an association between asymmetrical brain function and lymphocyte reactivity in mice selected for right- and left-paw preference. Left-handed mice, in comparison to right-handers, exhibit higher mitogen-induced T-lymphocyte proliferation. Using a cortical lesion paradigm in mice, it has been previously shown that each hemicortex modulates in opposite directions lymphocyte reactivity. In these experiments, the role of the brain cortex in the association between paw preference and immune reactivity was assessed by studying mitogen-induced lymphoproliferation in left- and right-handed mice after right or left-cortical ablation. The difference in T-lymphocyte responsiveness between right- and left-handed mice persisted after right lesions but was abolished after left lesions. This immunological effect of left cortical ablation is hypothesized to involve the hypothalamic dopaminergic neurons.

Analysis of Variance

Different responsiveness of spleen lymphocytes from two lines of psychogenetically selected rats (Roman high and low avoidance).

Roman high- (RHA) and low-avoidance (RLA) rats have been genetically selected on the basis of their active avoidance behavior, and have been shown to differ on numerous behavioral, neurochemical and neuroendocrine parameters, especially in response to stress. We investigated the activity of splenic lymphocytes in vitro. Natural killer cell activity against YAC-1 tumoral cells and the mitotic response to plant lectins concanavalin A and phytohemagglutinin were much lower for lymphocytes isolated from RHA rats, in males as well as in females. The difference between the two strains was even larger when measured in a stressed state, immediately after active avoidance learning. On the other hand, the mitotic response to bacterial lipopolysaccharide, a B-cell-specific mitogen, was not different between the two lines, indicating that the difference in lymphocyte reactivity is limited to the T-lineage. The lower activity of T-cells in the RHA line had no consequence upon the ability of these animals to build up an antibody response against sheep red blood cells. These results indicate that Roman lines are an interesting animal model for the study of the relationships between the brain and the immune system, as well as for the analysis of the genes involved in the control of behavior.

Animals

Natural killer cell activity is associated with brain asymmetry in male mice.

The brain is known to modulate the immune system in an asymmetrical way. In mice, there is an association between handedness and immune response and it has also been shown that hemicortical ablation has opposite effects on some immune parameters. An association between autoantibody production and paw preference was previously observed in female mice, but not in males, suggesting that the association between immune reactivity and functional brain asymmetry is a sex-dependent phenomenon. In three independent experiments, natural killer (NK) cell activity, lymphocyte subset distribution, and mitogen-induced lymphoproliferation were assessed in male C3H/OuJIco mice selected for handedness and after unilateral cortical ablation. Handedness was shown to be associated with NK cell activity but not with lymphocyte subset distribution or lymphoproliferation. Left-handers exhibited lower NK cell activity compared to right-handed or ambidextrous animals. In contrast to previous results in female mice, mitogen-induced lymphoproliferation was not associated with handedness in males. Left cortical ablations depressed NK cell activity, while right lesions had no effect. Neither left or right lesions affected lymphocyte subsets. No interaction between paw preference and side of the lesion was found in the modulation of NK cell activity. These and previous data show that the association between paw preference and immune reactivity varies according to the sex of the animal and the immunological parameters studied. This indicates that the brain may modulate different components of the immune system in different ways, through mechanisms apparently involving sex hormones.

Animals

Asymmetric distribution of brain monoamines in left- and right-handed mice.

Biogenic amine distributions analyzed in the cerebral neocortex, striatum, anterior hypothalamus, and bulbospinal region, were compared between both hemispheres of left- and right-handed mice. The handedness of mice was determined using a paw preference test. The animals were tested 5 times, once every two weeks, and the biochemical analysis was performed two weeks after the last behavioral evaluation. The results indicated that (1) asymmetrical monoaminergic concentrations exist in the mouse brain. Monoamine contents were found to be higher in the right parietal cortex and anterior hypothalamus than in the left ones; (2) besides the behavioral expression of handedness, left- and right-handed subpopulations of mice differ according to asymmetrical distributions of cortical and bulbospinal NE contents as well as DA turnover of the tuberoinfundibular system.

3,4-Dihydroxyphenylacetic Acid

The nucleus basalis is involved in brain modulation of the immune system in rats.

Male rats were subjected to bilateral or unilateral excitotoxic lesions of the nucleus basalis magnocellularis (NBM). Three weeks after surgery, mitogen-induced lymphoproliferation and natural killer (NK) cell activity were determined in the spleen. T-cell mitogenesis and NK cell activity were strongly enhanced after bilateral lesions but were not affected after right or left unilateral lesions. B-cell mitogenesis and blood T-cell subset distribution remained unchanged after bilateral or unilateral lesions of the NBM. These results demonstrate that NBM cells are involved in the complex interrelations existing between the central nervous system and the immune system.

Animals

Association between left-handedness and allergy: a reappraisal.

There are conflicting reports in the literature about the possible association between left-handedness and immune disorders, including autoimmune diseases as well as allergies. In this study we compared the distribution of right- and left-handers, assessed with the Edinburgh Handedness Inventory, in a group of patients consulting an allergy clinic and a control population with a similar sex and age distribution. There was no overall association between left-handedness and allergies, although we found a tendency towards left-handedness in patients whose allergic symptoms started before puberty, suggesting that left-handers may have an increased predisposition to allergic disease that manifests itself during early life.

Adolescent

Physiological basis for neuroimmunomodulation.

A large number of clinical and experimental observations indicate that immune responses may be modulated by the central nervous system (CNS). The immune system (IS) and CNS are known to communicate via the endocrine and the autonomic nervous systems. In this overview, we will focus on the immunomodulating role of neurotransmitters and neuropeptides. Immune cells appear to express membrane antigens similar to those of neural cells. Similarities re-enforce analogies between CNS and IS cells. The concept that the CNS modulates immune functions implies that the immune system feeds back information to the CNS. In fact, interleukins have neuroendocrine functions whether they are produced at the periphery by immune cells or at the CNS level by glial cells. Finally, the possible endocrine functions of lymphocytes are described and it is suggested that a complete regulatory loop between immune and neuro-endocrine systems exists. Studies in neuro-immunomodulation are of great importance from a theoretical point of view, the CNS-IS inter-relationships may not be considered only between the CNS and the periphery but also at the level of the immune micro-environment which may be considered as an immune-neuro-endocrine complex.

Adjuvants, Immunologic

Functional brain asymmetry and murine systemic lupus erythematosus.

The role of brain lateralization in antibody production was studied in a murine systemic lupus erythematosus model. Male and female New Zealand black mice that spontaneously produce pathogenic auto-antibodies directed against red blood cells and DNA, were divided into right- and left-handers using a paw preference test, and anti-erythrocyte and anti-DNA antibody production was repeatedly determined. In females, antibodies against erythrocytes and double-stranded DNA appeared earlier in left-handers. These results provide the first evidence of an association between a functional brain asymmetry and auto-antibody production and suggest the involvement of the central nervous system in the pathogenesis of autoimmune processes.

Aging

Brain neocortex modulation of mitogen-induced interleukin 2, but not interleukin 1, production.

Interleukin 2 (IL-2) production by splenic T cells stimulated by Concanavalin A was studied in mice after unilateral or bilateral brain neocortex ablation. The brain cortex was shown to modulate IL-2 production in an asymmetrical way. IL-2 levels were higher in animals with a right cortical lesion (group R) and lower in mice with a symmetrical lesion (group L) as compared to controls, differences between groups R and L being significant. Such variations of IL-2 production that were observed after unilateral lesions were abolished with bilateral cortical ablations. These results extend the immunoregulatory roles of the brain neocortex to IL-2 production by splenic T cells and may provide molecular support for neuro-immunological networks.

Animals

Hemispheric asymmetry in the effects of cerebral cortical ablations on mitogen-induced lymphoproliferation and plasma prolactin levels in female rats.

Female rats were subjected to unilateral left or right, bilateral, or sham ablation of the cerebral cortex. Eight weeks after surgery, the rats were sacrificed by decapitation and spleen cells were grown in culture for 96 h in the presence or absence of the T-cell mitogen concanavalin A or the B-cell mitogen lipopolysaccharide. Mitogenesis was determined by the addition of [3H]thymidine 24 h prior to harvesting. Both T- and B-cell mitogenesis were significantly depressed in subjects bearing cortical ablations in the right hemisphere, whereas left hemisphere ablation was without reliable effect. Prolactin in plasma collected at sacrifice was elevated in rats bearing right but not left hemisphere ablation and was significantly negatively correlated with both T- and B-cell immune responses. These results demonstrate a lateralized modulatory influence of cerebral cortex on immune function in female rats and they implicate elevated prolactin levels as a possible mediator of this effect.

Animals