Biomedical subjects

H Anisman

Publications and source records attributed to H Anisman.

At least 37 records · Page 2Linked to original sources

PubMed2000

Central infusion of interleukin-1 receptor antagonist fails to alter feeding and weight gain.

Interleukin-1 (IL-1) administered either i.p. or i.c.v. provokes sickness behaviors, including suppression of feeding. As well, the possibility exists that IL-1 contributes to the cascade of factors that regulate feeding under basal conditions. The current study assessed the contribution of IL-1 in the control of food intake and body weight under physiological conditions in male rats. Pretreatment with an IL- I receptor antagonist (IL-1ra, 16 mg/kg, i.p.) completely blocked the suppression of food intake produced by injection of IL-1beta (4 microg/kg, i.p.). However, neither daily injections of IL-1ra (16 mg/kg, i.p.) for 4 consecutive days nor infusion of IL-1ra (500 microg/day, i.c.v.) for 7 days altered daily food intake and the rate of body weight gain. These findings suggest while IL-1 may play a role in anorexia associated with sickness, this cytokine likely does not play a physiological role in the regulation of daily food intake and long-term energy balance.

Animals↗

PubMed2000

Kindling modulates the IL-1beta system, TNF-alpha, TGF-beta1, and neuropeptide mRNAs in specific brain regions.

Cytokines and neuropeptides may be involved in seizure-associated processes. Following amygdala kindling in rats, we determined alterations of IL-1beta, IL-1 receptor antagonist (IL-1Ra), IL-1 receptor type I (IL-1RI), IL-1 receptor accessory proteins (IL-1R AcPs) I and II, TNF-alpha, TGF-beta1, neuropeptide Y (NPY), glycoprotein 130 (gp 130) and pro-opiomelanocortin (POMC) mRNA levels in the parietal, prefrontal and piriform cortices, amygdala, hippocampus and hypothalamus. Messenger RNAs expression in all brain regions was determined 2 h or 3 weeks following the last generalized convulsive seizure triggered from the ipsilateral kindled amygdala. The same brain region sample was used to assay for changes of all mRNA components. The results show that the 2 h-kindled group exhibited a significant up-regulation of IL-1beta, IL-1RI, TNF-alpha and TGF-beta1 mRNAs in all three cortical brain regions, amygdala and hippocampus. The largest up-regulation occurred in the prefrontal cortex (about 30-fold induction for IL-1beta and TNF-alpha mRNAs). IL-1R AcP I and II mRNA levels were also up-regulated in the cortical regions. No changes in IL-1beta, IL-1RI or TNF-alpha mRNA levels occurred in the 3 week-kindled group. NPY mRNA levels increased in the hippocampus, prefrontal and piriform cortices in the 2 h-kindled group, while IL-1Ra, gp 130, or POMC mRNA levels did not change in any group. The overall profile of mRNA changes shows specificity of transcriptional modulation induced by amygdala kindling. The data support a role of cytokines and NPY in the adaptive mechanisms associated with generalized seizure activity, with implications for neuroprotection, neuronal dysfunction and vulnerability associated with epileptic activity.

Amygdala↗

PubMed2000

Neither acute nor chronic exposure to a naturalistic (predator) stressor influences the interleukin-1beta system, tumor necrosis factor-alpha, transforming growth factor-beta1, and neuropeptide mRNAs in specific brain regions.

Physical (neurogenic) stressors may influence immune functioning and interleukin-1beta (IL-1beta) mRNA levels within several brain regions. The present study assessed the effects of an acute or repeated naturalistic, psychogenic stressor (predator exposure) on brain cytokine and neuropeptide mRNAs. Acute predator (ferret) exposure induced stress-like behavioral effects, including elicitation of a startle response and reduced exploratory behaviors; these responses diminished after 30 sessions. Moreover, acute and repeated predator exposure, like acute restraint stress, increased plasma corticosterone levels measured 5 min later, but not 2 h after stressor exposure. In contrast, none of the stressors used influenced IL-1beta, IL-1 receptor antagonist, IL-1 receptor type I, IL-1 receptor accessory proteins I and II, or tumor necrosis factor-alpha mRNA levels in the prefrontal cortex, amygdala, hippocampus, or hypothalamus. Likewise, there were no stressor effects on transforming growth factor-beta1, neuropeptide Y, glycoprotein 130, or leptin receptor mRNAs in brain regions. Thus, the naturalistic/psychogenic stressor used does not affect any of the brain cytokine component mRNAs studied. It is suggested that this type of stressor activates homeostatic mechanisms (e.g., glucocorticoid release), which act to preclude brain cytokine alterations that would otherwise favor neuroinflammatory/neuroimmunological responses and the consequent increase of brain sensitivity to neurotoxic and neurodegenerative processes.

Analysis of Variance↗

PubMed2000

Lymphocyte proliferation among major depressive and dysthymic patients with typical or atypical features.

BACKGROUND: Depressive illness may be associated with immune and cytokine alterations. However, data are unavailable concerning functional immune changes associated with chronic, low-grade depression (dysthymia). Moreover, the contribution of the neurovegetative features of depression (e.g., altered sleep, eating) to the immune alterations remains to be determined. METHODS: Mitogen-stimulated cell proliferation was assessed in major depressive and dysthymic patients exhibiting either typical or atypical features. In a subset of patients, lymphocyte proliferation was also assessed before and after pharmacotherapy to determine whether alleviation of symptoms would be accompanied by normalization of immune functioning. RESULTS: Lymphocyte proliferation was reduced to a greater extent among dysthymic than among major depressive patients. Among dysthymic patients reduced cell proliferation was evident irrespective of symptom typicality; however, among major depressive patients the contribution of neurovegetative features varied with the specific mitogen used. Symptom alleviation following antidepressant treatment was not accompanied by normalization of cell proliferation. LIMITATIONS: Patients received 12 weeks of antidepressant treatment, and more sustained therapy may be required for normalization of immune activity. As well, conclusions concerning normalization of immune functioning in drug-treated major depressive patients requires that a greater number of patients be assessed. CONCLUSIONS: As the immune variations were more pronounced in dysthymia than in major depression, chronicity of illness may be a pertinent factor in promoting immune disturbances. This does not exclude the possibility that depression is associated with immune activation, which then provokes suppression of other aspects of immunity. As well, it is conceivable that immune alterations indirectly contribute to the symptoms accompanying depressive state, although it does not appear that variations of lymphocyte proliferation are associated with neurovegetative status.

Adult↗

PubMed2000

A prospective study of neuroendocrine and immune alterations associated with the stress of an oral academic examination among graduate students.

Stressful experiences may influence neuroendocrine, immune and cytokine functioning, as well as physical and psychological well being. The present prospective investigation assessed physiological and behavioral variations in anticipation of a critical oral academic examination among graduate students (i.e. related to a dissertation or comprehensive defense). Relative to matched control subjects, plasma cortisol levels were elevated among graduate students, especially females, 1 h prior to the oral examination, but not 6-8 weeks earlier (at about the time of the submission of the written document). In contrast, mitogen-stimulated (Con-A) lymphocyte proliferation was only reduced 6-8 weeks before the examination. Neither adrenocorticotrophic hormone (ACTH), prolactin, serum interleukin-1beta (IL-1beta) nor mitogen stimulated IL-1beta production was influenced at any time. Although, graduate students did not differ from controls with respect to perceived stress and feelings of mastery, they reported more frequent malaise (e.g. headaches, sore throat, fatigue) than did controls. The present findings suggest that during the course of lengthy anticipatory periods preceding a scheduled stressor, different stress-sensitive, situation-dependent biological processes may be engendered. It is further suggested that cortisol release is most closely aligned with immediate threats, while the immune alterations are sensitive to more distal events, or are subject to adaptation in response to a protracted stressor.

Adrenocorticotropic Hormone↗

PubMed2000

Synergistic effects of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha: central monoamine, corticosterone, and behavioral variations.

The proinflammatory cytokines interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) influence neuroendocrine activity, promote central neurotransmitter alterations, and induce a constellation of symptoms collectively referred to as sickness behaviors. These cytokines may also elicit anxiety and anhedonia, and have been associated with psychological disturbances in humans. In the present investigation, systemic IL-1beta and TNF-alpha dose-dependently and synergistically disrupted consumption of a highly palatable food source (chocolate milk), possibly reflecting anorexia or anhedonia engendered by the treatments. As well, these cytokines synergistically increased plasma corticosterone levels. Although IL-1beta and TNF-alpha provoked variations of amine turnover in the hypothalamus, locus coeruleus, and central amygdala, synergistic effects were not evident in this respect. Nevertheless, in view of the central amine variations induced by the cytokines, it is suggested that immune activation may come to influence complex behavioral processes, as well as affective state.

Animals↗

PubMed2000

Dysthymia: a review of pharmacological and behavioral factors.

Although dysthymia, a chronic, low-grade form of depression, has a morbidity rate as high as that of major depression, and increases the risk for major depressive disorder, limited information is available concerning the etiology of this illness. In the present report we review literature concerning the biological and characterological features of dysthymia, the effectiveness of antidepressant treatments, the influence of stressors in the precipitation and maintenance of the disorder, and both quality of life and psychosocial correlates of the illness. We also provisionally suggest that dysthymia may stem from disturbances of neuroendocrine and neurotransmitter functioning (eg, corticotropin releasing hormone and arginine vasopressin within the hypothalamus, or alternatively monoamine variations within several extrahypothalamic sites), and may also involve cytokine activation. The central disturbances may reflect phenotypic variations of neuroendocrine processes or sensitization of such mechanisms. It is suggested that chronic stressor experiences or stressors encountered early in life lead to the phenotypic neurochemical alterations, which then favor the development of the dysthymic state. Owing to the persistence of the neurochemical disturbances, vulnerability to double depression is increased, and in this instance treatment with antidepressants may attenuate the symptoms of major depression but not those of the basal dysthymic state. Moreover, the residual features of depression following treatment may be indicative of underlying neurochemical disturbances, and may also serve to increase the probability of illness recurrence or relapse.

Comorbidity↗

PubMed2000

Acoustic startle and fear-potentiated startle in rats selectively bred for fast and slow kindling rates: relation to monoamine activity.

The acoustic startle response, prepulse inhibition, fear-potentiated startle and monoamine activity induced by either, a novel stimulus or a cue previously paired with foot-shock (fear-conditioning), were assessed in rats selectively bred for differences in amygdala excitability (Fast vs. Slow kindling epileptogenesis). Comorbid differences of anxiety, which were dependent both on the rats' behavioural style and the kind of stressor, also characterized these strains. In the present investigation, Slow rats exhibited a greater startle reflex to noise relative to Fast rats, suggesting differences in generalized anxiety, but similar rates of startle habituation and prepulse inhibition. The fear-potentiated startle, however, was greater in Fast rats. When movement of the rat was restricted in a new environment, presentation of a novel stimulus (light) increased norepinephrine, dopamine and/or serotonin activity in brain regions typically associated with stressors (e.g. locus coeruleus, paraventricular hypothalamic nucleus). Generally, these effects were more pronounced in Fast rats, and norepinephrine utilization in the central amygdala was particularly highlighted in response to a conditioned fear stimulus. Thus, while generalized anxiety appeared greater in Slow rats, behavioural and central neurochemical reactivity in response to novel stimuli and to fear-eliciting stimuli, was greater in Fast rats. Similarly, basal dopamine activity in the prefrontal cortex was greater in Fast rats, but dopamine utilization elicited by a novel stimulus was more pronounced in Slow rats. This suggested that relative to Slow rats, dopamine neurons in prefrontal cortex of Fast rats do not react normally to environmental stimuli, and this phenomenon could lead to disturbances of attention or impulsivity.

Acoustic Stimulation↗

PubMed2000

Central monoamine activity following acute and repeated systemic interleukin-2 administration.

Interleukin-2 (IL-2), together with other cytokines, may be involved in communication between the immune system and the CNS. Moreover, IL-2 alterations have been implicated in psychiatric disorders, and IL-2 immunotherapy may engender neuropsychiatric and cognitive disturbances. Given the presumed relationship between mood disturbances and monoamine activity, the present investigation was undertaken to determine the central monoamine alterations associated with acute and repeated systemic IL-2 administration in mice. Acute, systemic IL-2 (0.55-17.6 x 10(3) IU) did not influence plasma adrenocorticotropic hormone or corticosterone levels, but increased the utilization of norepinephrine (NE) within the paraventricular nucleus of the hypothalamus. In contrast to the effects of acute IL-2 administration, when administered repeatedly (for 7 days), IL-2 increased NE utilization within the median eminence plus arcuate nucleus and in the hippocampus, and to a lesser extent in the central amygdala and medial prefrontal cortex. These changes in utilization were accompanied by increased levels of NE within the median eminence plus arcuate nucleus and central amygdala, and reduced NE within the locus coeruleus. As well, serotonin (5-hydroxytryptamine; 5-HT) levels were altered within the hippocampus and prefrontal cortex, and dopamine turnover was reduced within the caudate and substantia nigra. The finding of altered central neurotransmitter activity needs to be considered in the context of the marked cognitive/memory impairments, as well as the neuropsychiatric symptoms, which are associated with IL-2 immunotherapy in humans.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1999

Interleukin-1 beta production in dysthymia before and after pharmacotherapy.

BACKGROUND: Like major depression, dysthymia has been associated with elevated production of interleukin-1 (IL-1 beta) in mitogen-stimulated lymphocytes. In the present investigation, we assessed whether the elevated IL-1 beta production in dysthymic patients would normalize following treatment with sertraline. METHODS: The production of IL-1 beta was determined in dysthymic patients and in nondepressed control subjects. Patients then received 12 weeks of doses of either sertraline or placebo in a double-blind trial, after which cytokine production was again determined. RESULTS: Basal IL-1 beta was elevated in dysthymic patients relative to control subjects. Cytokine production was modestly correlated with the severity of symptoms and with the age of illness onset. Relative to placebo treatment, sertraline attenuated the symptoms of depression; however, this was not accompanied by normalization of IL-1 beta production. CONCLUSIONS: While dysthymia is associated with elevated IL-1 beta production, the failure for the cytokine to normalize following symptom alleviation suggests that either the IL-1 beta may be a trait marker of the illness, or that more sustained treatment is necessary to reduce cytokine production. Given the neuroendocrine and central neurochemical consequences of exogenously administered IL-1 beta, the possibility ought to be explored that increased IL-1 beta production may play a role in the pathophysiology of dysthymia.

Adult↗

PubMed1999

Effects of acute restraint stress on endogenous adrenomedullin levels.

Adrenomedullin (ADM) is a 52 amino acid peptide, with a potent hypotensive/vasodilatory action. Levels of ADM are significantly elevated in patients with hypertension, and it has been postulated that such stressor-related increases may serve a regulatory or protective function. The current study assessed the effects of acute restraint stress on ADM levels in regions of the brain, plasma and peripheral tissue including heart, lung and the adrenal glands of rats. This stressor, known to stimulate sympathetic activity as well as the hypothalamic-pituitary adrenal (HPA) axis, produced a significant increase in ADM levels in the pituitary gland, plasma and adrenal glands, all of which are key components of the HPA axis. The results suggest a regulatory and/or protective role for ADM in countering HPA activation following a variety of physiological and psychological stressors.

Acute Disease↗

PubMed1999

Influence of psychogenic and neurogenic stressors on neuroendocrine and central monoamine activity in fast and slow kindling rats.

The central neurochemical and neuroendocrine effects of a psychogenic (ferret exposure) and a neurogenic (restraint) stressor were assessed in rats that had been selectively bred for differences in amygdala excitability manifested by either Fast or Slow amygdala kindling epileptogenesis. While these rat lines differ in their emotionality, their behavioral styles were dependent on the nature of the stressor to which they were exposed. During restraint, the Slow rats were mostly immobile, while Fast rats persistently struggled. In contrast, Fast rats were more immobile in response to the ferret. Yet, the more emotional Slow rats exhibited a greater corticosterone response to the ferret, while comparable corticosterone responses between lines were evident following restraint. Although both stressors influenced norepinephrine (NE), dopamine (DA) and/or serotonin (5-HT) activity in brain regions typically associated with stressors (e.g., locus coeruleus, paraventricular nucleus of the hypothalamus, nucleus accumbens, prefrontal cortex), considerable amine alterations were evident in the medial and basolateral amygdala nuclei, but not in the central nucleus. Moreover, greater NE changes were apparent in the medial amygdala of the left hemisphere. Similarly, DA alterations also were greater in the left medial amygdala in response to stressors. Despite very different behavioral styles, however, the two lines often exhibited similar amine alterations in response to both stressors.

Animals↗

PubMed1999

Sensitization to the effects of tumor necrosis factor-alpha: neuroendocrine, central monoamine, and behavioral variations.

Consistent with the proposition that cytokines act as immunotransmitters between the immune system and the brain, systemic administration of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha; 1.0-4.0 microg) induced mild illness in CD-1 mice, increased plasma corticosterone concentrations, and altered central norepinephrine, dopamine, and serotonin turnover. The actions of TNF-alpha were subject to a time-dependent sensitization effect. After reexposure to a subeffective dose of the cytokine (1.0 microgram) 14-28 d after initial treatment, marked illness was evident (reduced consumption of a palatable substance and diminished activity and social exploration), coupled with an elevation of plasma corticosterone levels. In contrast, cytokine reexposure 1-7 d after initial treatment did not elicit illness, and at the 1 d interval the corticosterone response to the cytokine was reduced. The increase of norepinephrine release within the paraventricular nucleus of the hypothalamus, as reflected by elevated accumulation of 3-methoxy-4-hydroxyphenylglycol, was augmented at the longer reexposure intervals. In contrast, within the central amygdala and the prefrontal cortex TNF-alpha reexposure at the 1 d interval was associated with a pronounced sensitization-like effect, which was not apparent at longer intervals. Evidently, systemic TNF-alpha proactively influences the response to subsequent treatment; however, the nature of the effects (i.e., the behavioral, neuroendocrine, and central transmitter alterations) vary over time after initial cytokine treatment. It is suggested that the sensitization may have important repercussions with respect to cognitive effects of TNF-alpha and may also be relevant to analyses of the neuroprotective or neurodestructive actions of cytokines.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1999

Short- and long-periods of neonatal maternal separation differentially affect anxiety and feeding in adult rats: gender-dependent effects.

Environmental manipulations during early development can induce permanent alterations in hypothalamic-pituitary-adrenal (HPA) and behavioral responses to stressors. However, little is known about the impact of early life experiences on appetitive responses. The present investigation assessed the effects of brief handling/separation or protracted separation from the dams, on feeding and anxiety responses during development. During the first 3 weeks post-partum, Sprague-Dawley rat pups were exposed daily to either brief (15 min) handling/isolation (H), a more protracted (3 h) period of maternal separation (MS), or were not handled (NH). When tested on the elevated plus-maze (at 5-6 weeks) H groups displayed less anxiety than NH gender-matched controls. Surprisingly, so did the MS females. At weaning (Day 22), the MS rats weighed significantly less than both the H and NH animals; the difference between the H and MS was more robust and persisted throughout the experiment (D 62). The H animals of both genders, and the females of the MS group, consumed more of the palatable 'snack' than their NH counterparts. The feeding suppressant response to the various satiety peptides (bombesin, cholecystokinin, and amylin) was not affected by the early life experience, with exception of cholecystokinin (CCK) effects, which were more pronounced in H and MS males. These results suggest that early life events may contribute to anxiety and/or ingestive disorders such as anorexia nervosa, bulimia and obesity.

Amyloid↗

PubMed1999

Stressor-induced alterations in serotonergic activity in an animal model of depression.

The present study examined the effect of two neurogenic stressors (air puff and restraint) and a metabolic stressor (lipopolysaccharide; LPS 100 microg/kg, i.p.) on accumbal serotonergic neurotransmission in the olfactory bulbectomized (OB) rat model of depression. Both air puff and restraint stress caused greater increases in accumbal 5-HIAA in OB than in sham-operated rats. In contrast, bulbectomy resulted in a blunted serotonergic response to a challenge with LPS (a metabolic stressor). In addition, OB rats displayed significantly lower basal levels of 5-HIAA than sham-operated counterparts, a finding consistent with previous reports of the OB rat being a model of hyposerotonergic depression. The relevance of these findings to stressor-provoked depressive-like behaviors in the OB rat are discussed.

Air↗

PubMed1999

Behavioral and neurochemical consequences of lipopolysaccharide in mice: anxiogenic-like effects.

Systemic administration of lipopolysaccharide (LPS) induces sickness behaviors, as well as alterations of hypothalamic-pituitary-adrenal functioning commonly associated with stressors. In the present investigation, it was demonstrated that systemic LPS treatment induced a sickness-like behavioral profile (reduced active behaviors, soporific effects, piloerection, ptosis), which appeared to be dependent upon the novelty of the environmental context in which animals were tested. As well, LPS induced anxiogenic-like responses, including decreased time spent in the illuminated portion of a light-dark box, reduced open-arm entries in a plus-maze test, and decreased contact with a novel stimulus object in an open-field situation. The behavioral changes were accompanied by increased plasma ACTH and corticosterone levels. As well, LPS induced increased turnover of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) in the paraventricular nucleus (PVN), median eminence plus arcuate nucleus, hippocampus, as well as NE turnover within the locus coeruleus and DA turnover within the nucleus accumbens. Although these neurochemical variations were reminiscent of those elicited by stressors, LPS was not particularly effective in modifying DA activity within the prefrontal cortex or NE within the amygdala, variations readily induced by stressors. Whether the LPS-induced anxiogenic-like responses were secondary to the illness engendered by the endotoxin remains to be determined. Nevertheless, it ought to be considered that bacterial endotoxin challenge, and the ensuing cytokine changes, may contribute to emotionality and perhaps even anxiety-related behavioral disturbances.

Adrenocorticotropic Hormone↗

PubMed1999

Alterations in immune functions during normal aging and Alzheimer's disease.

It is thought that aging induces immune changes, which are related to the pathophysiology of Alzheimer's disease (DAT). In this study, the total number of leukocytes, white blood cell differentiation, mitogen-induced lymphocytic proliferation, neutrophil phagocytosis and superoxide release, and prostaglandin E2 (PGE2) production by mitogen-stimulated whole blood cultures were comparatively investigated between healthy adults (range 22-45 years) and healthy elderly volunteers (range 70-91 years), and between DAT patients (range 56-94 years) and age-matched control subjects. Healthy elderly volunteers showed significantly lower phytohemagglutinin (PHA)-induced lymphocyte proliferation and percentage and absolute number of basophils than young volunteers. In normal volunteers, there were significant and negative correlations between age and the number of basophils. Patients with DAT showed a trend toward significantly higher PHA-induced lymphocyte proliferation and significantly decreased percentage and absolute number of large unstained cells than healthy volunteers. In DAT patients, the total number of leukocytes and the percentage and number of neutrophils were positively correlated with age. All other immune-inflammatory variables were not significantly altered either by the aging process or DAT. The present study suggests that aging and DAT may differently affect some immune variables.

Adult↗

PubMed1999

Anhedonic and anxiogenic effects of cytokine exposure.

Systemic interleukin IL-1 beta, TNF alpha, and IL-2 profoundly influenced central monoamine activity, as well as behavioral outputs. The effects of the various cytokines were clearly distinguishable from one another, although synergistic effects were detected between several of these cytokines and between the actions of cytokines and stressors. Acutely applied IL-2 appeared to affect reward processes, but did not affect anxiety. When chronically administered, this cytokine markedly influenced working memory in a spatial learning test. In contrast to IL-2, both IL-1 beta and TNF alpha appeared to provoke an anxiogenic action, and provoked clear signs of illness. While these cytokines induced anorexia, they did not appear to affect reward processes. IL-1 beta and TNF alpha were found to act synergistically, and the TNF alpha provoked a sensitization with respect to the action of subsequent TNF alpha treatment. The findings indicated that cytokine treatments profoundly influence extrahypothalamic neurochemical functioning and may thus impact on behavioral outputs. Analyses of the behavioral and neurochemical changes elicited by cytokines, and particularly TNF alpha, need to consider not only the immediate impact of such treatments, but also the proactive effects that may be engendered.

Animals↗