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Biomedical subjects

S Vitiello

Publications and source records attributed to S Vitiello.

At least 19 recordsLinked to original sources

Cell surface expression of polysialic acid on NCAM is a prerequisite for activity-dependent morphological neuronal and glial plasticity.

Polysialic acid (PSA) on the extracellular domain of the neural cell adhesion molecule (NCAM) reduces cell adhesion and is considered an important regulator of cell surface interactions. The hypothalamo-neurohypophysial system (HNS), whose glia, neurons, and synapses undergo striking, reversible morphological changes in response to physiological stimulation, expresses high levels of PSA-NCAM throughout life. Light and electron microscopic immunocytochemistry in normal rats and rats in which cell transport was blocked with colchicine showed that PSA-NCAM is expressed in both HNS neurons and glia, particularly at the level of astrocytic processes that envelop neuronal profiles and can undergo remodeling. Moreover, we confirmed that the overall levels of PSA-NCAM were not greatly altered by stimulation (lactation and chronic salt ingestion). Nevertheless, PSA is essential to morphological plasticity. Using comparative ultrastructural analysis, we found that, after specific enzymatic removal of PSA from NCAM by microinjection of endoneuraminidase close to the hypothalamic magnocellular nuclei in vivo, there was no apparent withdrawal of astrocytic processes nor any increase in synaptic contacts normally induced by lactation and dehydration. Our observations demonstrate, therefore, that expression of PSA on cell surfaces in the adult HNS is indispensable to its capacity for activity-dependent morphological neuronal-glial and synaptic plasticity. The carbohydrate PSA on NCAM can thus be considered a necessary permissive factor to allow neuronal and glial remodeling to occur whenever the proper inductive stimulus intervenes.

Animals↗

Evidence for a hypothalamic oxytocin-sensitive pattern-generating network governing oxytocin neurons in vitro.

During lactation and parturition, magnocellular oxytocin (OT) neurons display a characteristic bursting electrical activity responsible for pulsatile OT release. We investigated this activity using hypothalamic organotypic slice cultures enriched in magnocellular OT neurons. As shown here, the neurons are functional and actively secrete amidated OT into the cultures. Intracellular recordings were made from 23 spontaneously bursting and 28 slow irregular neurons, all identified as oxytocinergic with biocytin and immunocytochemistry. The bursting electrical activity was similar to that described in vivo and was characterized by bursts of action potentials (20.1 +/- 4.3 Hz) lasting approximately 6 sec, over an irregular background activity. OT (0.1-1 microM), added to the medium, increased burst frequency, reducing interburst intervals by 70%. The peptide also triggered bursting in 27% of nonbursting neurons. These effects were mimicked by the oxytocin receptor (OTR) agonist [Thr4, Gly7]-OT and inhibited by the OTR antagonist desGly-NH2d(CH2)5[D-Tyr2,Thr4]OVT. Burst rhythmicity was independent of membrane potential. Hyperpolarization of the cells unmasked volleys of afferent EPSPs underlying the bursts, which were blocked by CNQX, an AMPA/kainate receptor antagonist. Our results reveal that OT neurons are part of a hypothalamic rhythmic network in which a glutamatergic input governs burst generation. OT neurons, in turn, exert a positive feedback on their afferent drive through the release of OT.

Animals↗

Peripheral catecholamines are involved in the neuroendocrine and immune effects of LPS.

There is evidence for bidirectional communication between the brain and the immune system. The immune system is subjected to neuroendocrine influences and reciprocally the hypothalamopituitary-adrenal axis is modulated by immune signals. Lipopolysaccharides (LPS), used to mimic infectious/inflammatory diseases, induce a series of stress markers, including modifications of monoaminergic transmission, enhancement of HPA axis activity, and decreased immune activity. In the present work we investigated the participation of peripheral catecholamines in the immune and endocrine responses to LPS in vivo. We studied the effects of LPS after chemical sympathectomy using 6-hydroxydopamine (6-OHDA), which does not cross the brain-blood barrier (BBB) in adults when peripherally injected. 6-OHDA administration was able to interfere with the effects of LPS on immune cells; however, the effects depended on the lymphoid tissue tested. In fact, the depression of mitogenesis induced by LPS was reversed by 6-OHDA in the spleen but not in the thymus. Moreover, 6-OHDA also interfered with the endocrine modifications induced by LPS. This neurotoxin completely or partially inhibited the effect of LPS on ACTH and corticosterone secretion, respectively. Taken together, these results clearly demonstrate that in vivo, the peripheral sympathetic nervous system participates in the immune and endocrine effects of LPS.

Adrenocorticotropic Hormone↗

Modulation of immune reactivity by unilateral striatal and mesolimbic dopaminergic lesions.

Asymmetrical modulation of immune reactivity by central dopaminergic pathways was suggested by previous reports which described an association between alterations of immune response and peculiar patterns of dopamine asymmetries in pathological and physiological situations. In the present experiments, we studied the respective roles of the nigrostriatal and mesolimbic dopaminergic networks in the asymmetrical modulation of immune responses. Lymphocyte proliferation as well as natural killer (NK) cell activity were analysed in mice, 2 weeks after unilateral lesions of dopaminergic projections by in situ injection of 6-hydroxydopamine in the striatum or the nucleus accumbens. After lesions of the striatum, proliferation of splenic lymphocytes was impaired only in the right-lesioned group. Left-lesions appeared to not modify T lymphocyte reactivity. After lesions of the nucleus accumbens, no modification of T lymphocyte mitogenesis was observed but splenic NK cell activity was depressed in left-lesioned mice as compared with controls or right-lesioned animals. Proliferation of B lymphocytes was not affected by striatal or mesolimbic dopaminergic lesions. It was concluded that both striatal and mesolimbic dopaminergic pathways are asymmetrically involved in neuro-immunomodulation. These dopaminergic regions appear to function independently as the effective side as well as the immune parameters that were altered differ according to the structure lesioned.

Animals↗

Brain monoaminergic, neuroendocrine, and immune responses to an immune challenge in relation to brain and behavioral lateralization.

Host responses to immune challenges involve central neurotransmission, the hypothalamo-pituitary adrenal axis, and the immune system. In the present work, we investigated the possibility of an asymmetry in the modification of brain monoamine metabolism induced by a systemic injection of lipopolysaccharide (LPS) in adult female mice. We also studied the possible influence of behavioral lateralization, as assessed by a paw preference test, on the reactivity of the nervous, neuroendocrine, and immune systems to a LPS challenge. The results showed that LPS administration induced an enhanced brain activity as demonstrated by an increase in noradrenergic, serotoninergic, and dopaminergic metabolism. Increased serotonin metabolism, observed in the hypothalamus and hippocampus, only occurred on the left side. Furthermore, the increase in serotonin turnover in the medial hypothalamus, the elevation of plasma adrenocorticotropin levels, and the decrease in T lymphocyte proliferation were observed in right-handed and ambidextrous mice but not in left-handed animals. Taken together, the results demonstrate that an immune challenge could induce neurochemical, neuroendocrine, and immune responses similar to those of stress, suggesting that LPS may be a stress inducer. Interestingly, these responses that may be asymmetrically expressed appear to depend on behavioral lateralization.

Adrenocorticotropic Hormone↗

Distribution of brain monoamines in left- and right-handed mice injected with bacillus Calmette-Guerin.

Concentrations of brain monoamines from various cerebral structures were determined in right and left sides of the brain from female mice selected for paw preference and injected or not with BCG 8 weeks before. BCG-induced changes in brain monoamine distribution in prefrontal cortex, medial hypothalamus and brain stem were only observed in right-handers. In the posterior hypothalamus, even though there was no BCG effect, norepinephrine asymmetry observed in right-handed controls was suppressed after BCG-injection. Moreover, BCG-induced brain monoamine changes in right-handers mainly involved the right hemisphere except the NE decrease in brain stem which was left-sided. This work demonstrates that the injection of BCG leads to long lasting asymmetrical changes in brain monoamine distribution that furthermore depend on behavioral lateralization of mice.

3,4-Dihydroxyphenylacetic Acid↗

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↗

Prolonged increase of corticosterone secretion by chronic social stress does not necessarily impair immune functions.

The influence of a chronic social stress upon immunity was investigated in Wistar rats, submitted for four weeks to two different behavioral situations, balanced in a factorial design: housing with three females and membership rotation. The combination of these two factor led to adrenal enlargement (43.3%), thymus involution (39.5%) and increased basal corticosterone levels, all indices of activation of the hypothalamic-hypophysis-adrenal axis. However, neither natural killer cell activity, splenocyte reactivity to mitogen nor the rate of spontaneous development of antibodies against Mycoplasma pulmonis, a common pathogen of the respiratory tract, were changed in the endocrine activated animals. Analysis of the data on kinetics of stress at 1, 7 and 28 days after the initial mixing of the animals gave the same results. These data question the immunosuppressant activity usually conferred to corticosteroids, at least when adrenal hyperactivity is induced by chronic environmental stressors.

Adrenal Glands↗

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↗

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↗

[In vitro study of the cytotoxicity of inflammation mediators secreted around microencapsulated cells].

One of the implantation problems in immunoprotected living cells is the appearance of local inflammatory phenomena around microcapsules. Some of the mediators released in such pathophysiological conditions were tested. A toxic action of compounds such as elastase, collagenase was evidenced. Interleukins 1 and 2 revealed no cytotoxicity within the test limits on the experimental cellular model chosen. These results underline the importance of inflammatory mediators released by adjacent cells of the implant.

Animals↗

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↗

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↗