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PubMed2005

MHC peptides and the sensory evaluation of genotype.

Social interactions, such as finding and identifying a mate, often rely on the ability to sense molecular cues carrying information about genetic relationship and individuality. We summarize recent evidence for an unexpected mechanistic link between the immune and olfactory systems in enabling this identification process. In addition to their established role in the immune response, peptide ligands of major histocompatibility complex (MHC) molecules constitute a previously unknown family of social recognition signals detected by specific subsets of sensory neurons in the mammalian nose. This sensing of MHC peptides can be viewed as a form of functional genome analysis by the nose. Behavioral studies in mice and fish show that MHC peptides are accepted as olfactory cues that influence mate choice decisions and selective pregnancy failure. These findings provide a molecular mechanism by which an individual can sense the composition and compatibility of vital immune system molecules of a conspecific, with direct consequences for social behavior.

Animals↗
PubMed2000

Tissue distribution of the opioid receptor-like (ORL1) receptor.

The ORL1 receptor is a G protein-coupled receptor structurally related to the opioid receptors, whose endogenous ligand is the heptadecapeptide nociceptin/orphanin FQ. In this review, data which have contributed to the mapping of the anatomic distribution of the ORL1 receptor have been collated with an emphasis on their relation to physiological functions. The ORL1 receptor is widely expressed in the central nervous system, in particular in the forebrain (cortical areas, olfactory regions, limbic structures, thalamus), throughout the brainstem (central periaqueductal gray, substantia nigra, several sensory and motor nuclei), and in both the dorsal and ventral horns of the spinal cord. Regions almost devoid of ORL1 receptors are the caudate-putamen and the cerebellum. ORL1 mRNA and binding sites exhibit approximately the same distribution pattern, indicating that the ORL1 receptor is located on local neuronal circuits. The ORL1 receptor is also expressed at the periphery in smooth muscles, peripheral ganglia, and the immune system. The anatomic distribution of ORL1 receptor suggests a broad spectrum of action for the nociceptin/orphanin FQ system (sensory perception, memory process, emotional behavior, etc.).

Animals↗
PubMed1992

Inhibition of neutrophil chemotaxis and activation following decentralization of the superior cervical ganglia.

Recent studies have shown that bilateral decentralization (sympathectomy) of the superior cervical ganglia (SCG) of rats sensitized to the parasite Nippostrongylus brasiliensis attenuated the development of pulmonary inflammation following allergen challenge. Sympathectomy inhibited total leukocyte infiltration into lung lavage fluids, particularly neutrophil infiltration. To define the effects of decentralization of the SCG on neutrophil responses, peripheral blood neutrophils of rats were isolated and tested in in vitro chemotaxis and phagocytosis assays. Neutrophils from rats that were sympathectomized 7 days previously displayed a marked reduction in chemotaxis to N-formyl-methionyl-leucyl-phenylalanine and leukotriene B4 compared to neutrophils from sham-operated or unoperated groups. Although the degree of chemotaxis was greater in blood neutrophils from parasite-infected rats than from uninfected rats, sympathectomy markedly reduced the chemotactic responses of both groups. In addition, neutrophils of sympathectomized rats were unresponsive to lipopolysaccharide-induced metabolic activation as assessed by in vitro phagocytosis and oxidative reduction of nitroblue tetrazolium. Thus, decentralization of the SCG of rats affects the chemotactic responses and functions of neutrophils. Understanding the role of the sympathetic nervous system in modulating the behavior of neutrophils will shed light on the interactions between the nervous and immune systems.

Animals↗
PubMed1999

Implications of immune-to-brain communication for sickness and pain.

This review presents a view of hyperalgesia and allodynia not typical of the field as a whole. That is, exaggerated pain is presented as one of many natural consequences of peripheral infection and injury. The constellation of changes that results from such immune challenges is called the sickness response. This sickness response results from immune-to-brain communication initiated by proinflammatory cytokines released by activated immune cells. In response to signals it receives from the immune system, the brain orchestrates the broad array of physiological, behavioral, and hormonal changes that comprise the sickness response. The neurocircuitry and neurochemistry of sickness-induced hyperalgesia are described. One focus of this discussion is on the evidence that spinal cord microglia and astrocytes are key mediators of sickness-induced hyperalgesia. Last, evidence is presented that hyperalgesia and allodynia also result from direct immune activation, rather than neural activation, of these same spinal cord glia. Such glial activation is induced by viruses such as HIV-1 that are known to invade the central nervous system. Implications of exaggerated pain states created by peripheral and central immune activation are discussed.

Animals↗
PubMed1988

Self-care behaviors and informational needs of seropositive homosexual/bisexual men.

Patients with acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC) are developing beliefs, behaviors, and a knowledge bases that may affect their health status, sense of well-being, and health care needs. However, little documentation of these changes exists. Consequently, the purpose of this study was to describe AIDS beliefs, behaviors, and informational needs of homosexual/bisexual human immunodeficiency virus (HIV) seropositive patients 7 years into the epidemic. Data were collected once from 178 patients using a modified version of the AIDS Beliefs and Behaviors Questionnaire (ABBQ). Study results showed that in 1987, most outpatients (73%) in an AIDS epicenter wanted more information about building their immune systems. Few patients (12%) wanted more explicit information about safe sexual behaviors, although 3 years into the epidemic this information was a central concern. Results suggest that health professionals need to take an active role in monitoring and addressing patients' changing informational needs.

AIDS-Related Complex↗
PubMed2001

Social status in mice: behavioral, endocrine and immune changes are context dependent.

The aim of the present study was to investigate the effect of social status on the endocrine, immune and behavior response of male mice. We found that in mice reared in a group of siblings since weaning, no difference exists between dominants and subordinates in basal corticosterone level, in behavior in the open-field test (OFT) and in a series of immune parameters. These results suggest that living with siblings is not a stressful condition for either dominant or subordinate mice. Therefore, group-housed siblings can be regarded as a valid control group in social stress studies. When mice were subjected to chronic psychosocial stress for 21 days, four types of social outcome occurred: residents becoming dominants, intruders becoming subordinates, residents becoming subordinates and intruders becoming dominants. Interestingly, the behavioral profile in the OFT revealed a status-dependent effect, with resident dominants (RD) and intruder dominants (InD) showing the highest locomotor and exploratory activity, whereas the corticosterone level was higher than control for all four categories. In addition, a context-dependent effect emerged at the immune level: resident subordinates (RS) had a reduced splenocyte proliferation and IL-4 and IL-10 production. Mice in all the other three social ranks showed no immune alterations. Therefore, the loss of an individual's social rank position seems a promising field of study to investigate the psychological impact of stressful events.

Adjuvants, Immunologic↗
PubMed1990

Immobilization 12 days (but not one hour) earlier enhanced 2-deoxy-D-glucose-induced immunosuppression: evidence for stressor-induced time-dependent sensitization of the immune system.

1. Prior exposure to a stressor can either increase or decrease subsequent behavioral, neurochemical, and endocrine reactivity to stress, depending on the pattern of stress exposure. 2. Massed or frequent exposures typically induce a reduction in reactivity whereas intermittent or widely spaced exposures increase subsequent reactivity. 3. In the present study, the authors examined whether a single presentation of a temporally remote stressor would increase the immunosuppressive effects of a subsequent stressor. Specifically, the authors investigated the effectiveness of 2-deoxy-D-glucose (2-DG) in suppressing the responsiveness of splenic lymphocytes in male, Sprague-Dawley rats that received either no prior treatment, or immobilization either one hour or 12 days earlier. 4. Splenic lymphocyte responsiveness to the T-cell mitogens, Concanavalin A (Con-A) and phytohemagglutinin (PHA) was suppressed following a single injection of 2-DG. 5. The group exposed to the stress of immobilization one hour prior to 2-DG demonstrated a comparable level of immune suppression. 6. In contrast, animals immobilized 12 days prior to the administration of 2-DG showed a more pronounced suppression of immune responsiveness which was significantly greater than the other groups injected with 2-DG. 7. Neither the stress-induced elevation in corticosterone, nor the suppression of blood lymphocyte reactivity to Con-A and PHA was enhanced by prior immobilization. 8. The results indicate that the immunosuppressive effects of an acute stressor can sensitize with the passage of time.

Animals↗
PubMed1990

[Significance and possible role of reactive T-cell infiltrate in primary B-cell lymphoma of the skin].

Primary cutaneous B-cell lymphomas (pCBCLs) represent a distinctive group from both the clinical and histomorphologic point of view, and, when compared with node-based lymphomas, tend to have a much more indolent behavior. In light of current knowledge of Skin Immune System (SIS), the actual cutaneous origin of pCBCLs and their relationship to SIS are an interesting matter of debate. In 24 cases of pCBCLs, we evaluated the evolutionary modifications of reactive T-cell infiltrate and the morphologic evidence of High Endothelial Venules (HEV). The amount of reactive T-cells was inversely related to the growth rate of skin lesions; a significant correlation was found between amount of reactive T-cells and HEV expression. Interestingly, the dramatic reduction of reactive T-cells and rapid growth of neoplastic B-cells found in nodular, quickly growing lesions, does not however correlate with the quite good overall clinico-biologic behavior of pCBCLs.

Endothelium↗
PubMed1997

Animal well-being. IV. Specific assessment criteria.

A number of factors have potential use as indicators of animal well-being. Classic and practical criteria for assessing animal well-being are a combination of general health status, clinical signs of disease, and performance. Numerous regulatory mechanisms and systems are responsible for many neurochemical and endocrine changes in response to arousing and stimulating events. Neuroendocrine changes associated with aversive stimuli have been implicated in modulation of immune responses. Animal behavior and preference, which can be observed directly and noninvasively, can be useful in assessment of well-being. Aversive conditions, especially longer term, can cause morphologic and pathologic changes in some tissues.

Animal Diseases↗
PubMed2005

Down-regulation of dopamine transporter and abnormal behavior in STAT6-deficient mice.

To determine the role of STAT6 transcription factors in brain function, we performed a battery of mouse behavioral analyses of STAT6-deficient mice and made comparisons with wild-type mice. STAT6-deficient mice were significantly more hyperactive in the final two blocks of an open field test, indicating abnormal habituation in completing the task. Two learning tasks, a water maze and a passive avoidance test, were mastered by STAT6-deficient mice as effectively as the wild-type. RT-PCR analysis suggested that the levels of dopamine transporter (DAT) mRNA may be lower in the midbrain of the mutant. In agreement with the finding, subsequent Western blotting and immunohistochemical analysis demonstrated lower levels of DAT protein in the mutant striatum. These results lead to the proposal that, in addition to being a pivotal transcription factor in the immune system, STAT6 may be crucially implicated in mouse behavior by modulating the expression of neuronal genes such as DAT.

Animals↗
PubMed1995

Effect of bacterial endotoxin and interleukin-1 beta on hippocampal serotonergic neurotransmission, behavioral activity, and free corticosterone levels: an in vivo microdialysis study.

In this study the effect of immune system stimulation and intracerebroventricular (i.c.v.) administration of interleukin-1 beta (IL-1 beta) on hippocampal serotonergic neurotransmission, behavioral activity, and the hypothalamic-pituitary-adrenocortical (HPA) axis is described. An in vivo microdialysis method was used to measure hippocampal extracellular concentrations of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in conscious, freely moving rats. In addition, we established a method to continuously monitor free corticosterone levels in dialysates. Behavioral activity was scored by measuring the time during which rats were active (locomotion, grooming, eating, drinking). We found a significant, positive relationship between behavioral activity and hippocampal extracellular concentrations of 5-HT. Intraperitoneal (i.p.) administration of the bacterial endotoxin lipopolysaccharide (LPS; 30, 100, and 300 micrograms/kg body weight) produced an increase in the extracellular concentrations of 5-HT and 5-HIAA in the hippocampus, which was paralleled by a significant decline in behavioral activity and a marked increase in extracellular corticosterone levels. Thus, the close correlation between hippocampal extracellular 5-HT levels and behavioral activity observed in control rats was disrupted in the LPS-treated animals. The effects of i.p. LPS could be mimicked by i.c.v. application of recombinant human IL-1 beta (hIL-1 beta; 100 ng). i.c.v. pretreatment with the IL-1 receptor antagonist (IL-1ra; 10 micrograms) antagonized the hIL-1 beta-induced effects. IL-1ra showed no intrinsic effects. Furthermore, it was found that i.c.v. pretreatment with IL-1ra (10 micrograms) significantly attenuated the i.p. LPS-induced (100 micrograms/kg body weight) rise in hippocampal extracellular 5-HT levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Assessment of comfort and well-being in farm animals.

The assessment of comfort and well-being in farm animals is discussed in terms of physical damage, physiological responses and behavior. Injuries may be due to the physical environment or contact, such as aggression, with other animals. Animals may reduce the frequency of injuries by modifying their behavior. Evaluation of injuries requires a methodical assessment of specific areas of the body and examination of the facilities and behavior of the animal to determine cause. The physiological response of an animal is dependent upon its psychological response. The adrenal medullary and cortical responses represent distinct strategies that may occur simultaneously or independently of each other. Stress frequently results in suppression of immune responses, although some aspects of the immune system are enhanced. Inadequate or excessive motivation results in behavioral problems and facilities must accommodate the behavior of the animals. Methods of preference-testing have been improved to evaluate factors in the environment and assess motivation for specific behaviors more reliably. All of the methods used to assess comfort and well-being must consider the animal's ability to adapt to different environments. Although it remains difficult to assess comfort and well-being across systems, improvement within a system can be demonstrated.

Animal Husbandry↗
PubMed1993

Fibromyalgia, sleep disorder and chronic fatigue syndrome.

Various research studies show that the amalgam of disordered sleep physiology, chronic fatigue, diffuse myalgia, and cognitive and behavioural symptoms constitutes a non-restorative sleep syndrome that may follow a febrile illness, as in the chronic fatigue syndrome. Where rheumatic complaints are prominent such a constellation of disturbed sleep physiology and symptoms also characterizes the fibromyalgia disorder. In contrast to the chronic fatigue syndrome, fibromyalgia is associated with a variety of initiating or perpetuating factors such as psychologically distressing events, primary sleep disorders (e.g. sleep apnoea, periodic limb movement disorder) and inflammatory rheumatic disease, as well as an acute febrile illness. The chronic fatigue syndrome and fibromyalgia have similar disordered sleep physiology, namely an alpha rhythm disturbance (7.5-11 Hz) in the electroencephalogram (EEG) within non-rapid eye movement (NREM) sleep that accompanies increased nocturnal vigilance and light, unrefreshing sleep. Aspects of cytokine and cellular immune functions are shown to be related to the sleep-wake system. The evidence suggests a reciprocal relationship of the immune and sleep-wake systems. Interference either with the immune system (e.g. by a viral agent or by cytokines such as alpha-interferon or interleukin 2) or with the sleeping-waking brain system (e.g. by sleep deprivation) has effects on the other system and will be accompanied by the symptoms of the chronic fatigue syndrome.

Behavior↗
PubMedDate not supplied

The impact of stressors on immune and central neurotransmitter activity: bidirectional communication.

Antigenic challenge may have broad ranging effects which include not only immunological changes, but also endocrine and central neurotransmitter repercussions, and may thus elicit profound behavioral sequelae. Commensurate with the notion that bidirectional communication exists between the immune and central nervous systems it has been demonstrated that manipulations which influence central neurotransmitter or endocrine activity provoke alterations of immune functioning, and conversely immunological alterations will affect central neurotransmitter and endocrine activity. It seems, as well, that environmental stressors may provoke marked alterations of the activity of each of these systems. Indeed, in several respects the variables that influence vulnerability to stressor-provoked neurotransmitter changes, likewise affect the immunological alterations engendered by stressors. Moreover, immunological challenges will affect central neurotransmitter functioning in much the same way as stressors provoke such effects. It is thought that immune derived products (including cytokines as well as peptide hormones) may act directly or indirectly to moderate neurotransmitter functioning, and centrally derived neurotransmitters and hormones may affect receptors present on lymphocytes. In accordance with earlier suggestions, it is maintained that the immune system may be acting as a sensory organ informing the brain of the presence of antigenic challenges, and the brain may interpret such challenge as a stressor, hence leading to behavioral alterations.

Animals↗
PubMed2002

CRF(2) Receptors: An Emerging Role in Anxiety.

Corticotropin-releasing factor (CRF) systems are major regulators of stress-induced endocrine, autonomic, immune and behavioral responses. Studies indicate that two high affinity CRF receptors designated CRF(1) and CRF(2) mediate the actions of CRF. Dysregulation of this CRF system, which may involve excessive secretion of the CRF peptide and/or alterations in CRF receptor functions, may facilitate the occurrence of stress-induced disorders including anxiety and depression. In the last few years, several specific CRF(1) receptor antagonists were developed and shown to be effective in reducing animal anxiety and depression-like behavior. In contrast, comparable information concerning the role of the CRF(2) receptor has not been available. However, recent preclinical studies demonstrate that CRF(2) receptors may also mediate anxiety behavior. Although the involvement of both CRF(1) and CRF(2) receptors underscores the complexity and diversity in CRF receptor systems underlying the neurobiology of anxiety, the development of CRF receptor antagonists that are capable of binding to one or both receptors may lead to novel pharmacotherapies for the treatment of psychopathology.(c) 2002 Prous Science. All rights reserved.

Journal Article↗
PubMed1991

Behavioral aspects of stress.

Many researchers view stress theory as having evolved from a specific response for each specific stimulus, through a standardized general adaptation syndrome for a wide variety of stressors, to a newly hypothesized model that suggests a standardized physiological response for psychological stressors and specific homeostatic responses for physical stressors. Stressors can originate from within an individual (endogenous) or from the environment (exogenous). A sense of control over one's environment (exogenous stimuli) and predictability of stimuli are extremely important in determining the potency of psychological stressors. The performance of highly repetitive, stereotyped behaviors has been shown to help animals cope with environments containing little or unvaried stimulation. Chronic psychological stressors are the most problematic area of stress research and animal care. Animals may respond behaviorally to chronic stressors by either achieving adaptation or by showing such conditions as learned helplessness, intensification of drives, stereotyped behavior, and absence of normal behaviors. A chronic endogenous buildup of motivation to perform specific behaviors that an animal has been prevented from performing can be quantified and result in animals displaying signs of chronic stress, i.e., altered metabolism (hormones), suppressed immune system, and learned helplessness. It is of paramount importance that the behavioral and physiological variables utilized in stress research be relevant to the particular species and questions under study.

Acute Disease↗