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Biomedical subjects

Hymie Anisman

Publications and source records attributed to Hymie Anisman.

At least 19 recordsLinked to original sources
PubMed2007

Ruminative coping among patients with dysthymia before and after pharmacotherapy.

The pivotal role of rumination in relation to other coping strategies was assessed in chronically depressed (dysthymic disorder) individuals versus nondepressed controls. Individuals with dysthymia demonstrated elevated use of rumination and other emotion-focused strategies (emotional expression, emotional containment, self- and other-blame). Among patients with dysthymia, rumination was linked to this limited array of emotion-focused efforts and diminished use of cognitive disengagement, whereas among controls, rumination was correlated with a broad constellation of problem- and emotion-focused strategies. Following 12 weeks of pharmacotherapy (sertraline), despite attenuation of depressed mood and reduced rumination, the limited relations between rumination and emotion-focused efforts persisted. Inflexibility in the ability to combine various coping efforts effectively may be characteristic of individuals with dysthymia, potentially increasing risk for recurrence.

Adaptation, Psychological↗
PubMed2006

The role of gastrin-releasing peptide on conditioned fear: differential cortical and amygdaloid responses in the rat.

RATIONALE: Bombesin (BB), an amphibian peptide, was shown to affect the expression of the stress response. However, the physiological role of the mammalian counterparts of BB in mediating anxiety and fear responses remain to be characterized. OBJECTIVE: This study examined the effects of gastrin-releasing peptide (GRP), a mammalian analogue of BB, and its receptor antagonist, BW2258U89, on conditioned emotional response (CER), using fear conditioning. MATERIALS AND METHODS: The effects of these compounds on contextual and cued fear conditioning were assessed after direct bilateral infusions into the prelimbic (PrL) cortex, infralimbic (IL) cortex or central nucleus of the amygdala (CeA). RESULTS: GRP (300 ng) microinjected into each of the three target nuclei significantly reduced freezing to contextual cues. Similarly, in the cued portion of CER, GRP administered to the IL cortex significantly reduced freezing. Administration of BW2258U89 resulted in dose-dependent and site-specific effects. At the IL cortex, the 50 ng dose decreased freezing to both contextual and cued fear conditioning. At the CeA, the 300 ng dose also decreased freezing, but at the 50 ng dose, it increased contextual freezing. At the PrL cortex, BW2258U89 did not affect freezing. CONCLUSIONS: These results illustrate that (1) GRP system(s) can significantly affect the expression of learned fear, (2) some of the relevant brain sites mediating these effects include the PrL, IL and the CeA, and (3) such effects may be dependent upon whether responses were evoked by environmental contextual fear cues or by specific auditory cues that were explicitly paired with an aversive stimulus.

Amygdala↗
PubMed2006

Bombesin receptors as a novel anti-anxiety therapeutic target: BB1 receptor actions on anxiety through alterations of serotonin activity.

The effects of PD 176252 [3-(1H-indol-3-yl)-N-[1-(5-methoxy-pyridin-2-yl)-cyclohexylmethyl]-2-methyl-2-[3-(nitro-phenyl)ureido]propionamide], a nonpeptide bombesin (BB) BB1/BB2 receptor antagonist, were assessed in rats using several ethologically relevant tests of anxiety. Consistent with a role for the bombesin family of peptides in subserving anxiety behaviors, the antagonist increased social interaction (3.75 and 7.5 mg/kg, i.p.), dose-dependently attenuated the number of vocalizations emitted by guinea pig pups separated from their mother (1-30 mg/kg, i.p.), reduced latency to approach a palatable snack in an anxiogenic (unfamiliar) environment, and reduced the fear-potentiated startle response (5 and 10 mg/kg, i.p., and 100-200 ng per rat, i.c.v.). When administered directly to the dorsal raphé nucleus (DRN), PD 176252 (20-500 ng) increased social interaction under aversive conditions, as did the 5-HT1A receptor agonist 8-hydroxy-2(di-n-propylamino)tetralin (50 ng). Furthermore, intra-DRN microinfusion of the peptide antagonist (PD 176252) suppressed, whereas its agonist [neuromedin B (NMB)-30] promoted, the in vivo release of 5-HT in the ventral hippocampus. In parallel, the suppressed social interaction elicited by intra-DRN administration of NMB was attenuated by a systemically administered 5-HT2C (but not 5-HT1A) receptor antagonist. Together, these findings suggest that endogenous BB-like peptides at the DRN evoke the release of 5-HT from the limbic nerve terminals originating from the raphé, specifically at the ventral hippocampus, resulting in anxiogenesis. The finding that this action was attenuated by BB receptor (BB1 and/or BB2) antagonists suggests that these compounds may represent a novel class of anxiolytic agents.

Animals↗
PubMed2006

Effects of acute or chronic omega-3 and omega-6 polyunsaturated fatty acid treatment on behavioral, neuroendocrine and cytokine changes elicited by exogenous interleukin-1beta challenge.

Chronic omega-3 or omega-6 polyunsaturated fatty acid (n-3; n-6 respectively) treatment attenuated human interleukin-1beta (hIL-1beta; 5.0 microg/kg)-elicited rise of circulating ACTH levels and attenuated the sickness behavior and locomotor suppression elicited by the cytokine. Furthermore, hIL-1beta markedly elevated circulating levels of plasma IL-6, an effect attenuated by n-3, but not n-6 treatment. Such protective effects were not evident upon short-term (3 day) n-3 exposure. These results demonstrate that long-term administration of either n-3 or n-6 confers protection against several neuroendocrinological, immunological and behavioral actions of hIL-1beta challenge, although in general the effects of n-3 were more pronounced.

Adrenocorticotropic Hormone↗
PubMed2006

Maternal factors and monoamine changes in stress-resilient and susceptible mice: cross-fostering effects.

Genetic factors influence stressor-provoked monoamine changes associated with anxiety and depression, but such effects might be moderated by early life experiences. To assess the contribution of maternal influences in determining adult brain monoamine responses to a stressor, strains of mice that were either stressor-reactive or -resilient (BALB/cByJ and C57BL/6ByJ, respectively) were assessed as a function of whether they were raising their biological offspring or those of the other strain. As adults, offspring were assessed with respect to stressor-provoked plasma corticosterone elevations and monoamine variations within discrete stressor-sensitive brain regions. BALB/cByJ mice demonstrated poorer maternal behaviors than C57BL/6ByJ dams, irrespective of the pups being raised. In response to a noise stressor, BALB/cByJ mice exhibited higher plasma corticosterone levels and elevated monoamine turnover in several limbic and hypothalamic sites. The stressor-provoked corticosterone increase in BALB/cByJ mice was diminished among males (but not females) raised by a C57BL/6ByJ dam. Moreover, increased prefrontal cortical dopamine utilization was attenuated among BALB/cByJ mice raised by a C57BL/6ByJ dam. These effects were asymmetrical as a C57BL/6ByJ mice raised by a BALB/cByJ dam did not exhibit increased stressor reactivity. It appears that stressors influence multiple neurochemical systems that have been implicated in anxiety and affective disorders. Although monoamine variations were largely determined by genetic factors, maternal influences contributed to stressor-elicited neurochemical changes in some regions, particularly dopamine activation within the prefrontal cortex.

Animals↗
PubMed2006

Maternal programming of defensive responses through sustained effects on gene expression.

There are profound maternal effects on individual differences in defensive responses and reproductive strategies in species ranging literally from plants to insects to birds. Maternal effects commonly reflect the quality of the environment and are most likely mediated by the quality of the maternal provision (egg, propagule, etc.), which in turn determines growth rates and adult phenotype. In this paper we review data from the rat that suggest comparable forms of maternal effects on defensive responses stress, which are mediated by the effects of variations in maternal behavior on gene expression. Under conditions of environmental adversity maternal effects enhance the capacity for defensive responses in the offspring. In mammals, these effects appear to 'program' emotional, cognitive and endocrine systems towards increased sensitivity to adversity. In environments with an increased level of adversity, such effects can be considered adaptive, enhancing the probability of offspring survival to sexual maturity; the cost is that of an increased risk for multiple forms of pathology in later life.

Adaptation, Psychological↗
PubMed2006

Calpain-regulated p35/cdk5 plays a central role in dopaminergic neuron death through modulation of the transcription factor myocyte enhancer factor 2.

The mechanisms underlying dopamine neuron loss in Parkinson's disease (PD) are not clearly defined. Here, we delineate a pathway by which dopaminergic loss induced by 1-methyl-4-phenyl 1,2,3,6 tetrahydropyridine (MPTP) is controlled in vivo. We reported previously that calpains play a central required role in dopamine loss after MPTP treatment. Here, we provide evidence that the downstream effector pathway of calpains is through cyclin-dependent kinase 5 (cdk5)-mediated modulation of the transcription factor myocyte enhancer factor 2 (MEF2). We show that MPTP-induced conversion of the cdk5 activator p35 to a pathogenic p25 form is dependent on calpain activity in vivo. In addition, p35 deficiency attenuates MPTP-induced dopamine neuron loss and behavioral outcome. Moreover, MEF2 is phosphorylated on Ser444, an inactivating site, after MPTP treatment. This phosphorylation is dependent on both calpain and p35 activity, consistent with the model that calpain-mediated activation of cdk5 results in phosphorylation of MEF2 in vivo. Finally, we provide evidence that MEF2 is critical for dopaminergic loss because "cdk5 phosphorylation site mutant" of MEF2D provides neuroprotection in an MPTP mouse model of PD. Together, these data indicate that calpain-p35-p25/cdk5-mediated inactivation of MEF2 plays a critical role in dopaminergic loss in vivo.

Animals↗
PubMed2005

Corticotropin-releasing hormone, arginine vasopressin, gastrin-releasing peptide, and neuromedin B alterations in stress-relevant brain regions of suicides and control subjects.

BACKGROUND: Postmortem levels of several stress- and depression-relevant neuropeptides were assessed in brain regions of depressed suicides relative to control subjects that had died of other causes. METHODS: Brains of suicides and those that died from other causes were collected soon after death (typically <6 hours). Immunoreactivity levels (ir) of corticotropin-releasing hormone (CRH-ir) and arginine vasopressin (AVP-ir), and the bombesin analogs, gastrin-releasing peptide (GRP-ir), and neuromedin B (NMB-ir), were assessed. RESULTS: Levels of CRH-ir among suicides were elevated in the locus coeruleus (LC), frontopolar, dorsolateral prefrontal (DMPFC) and ventromedial prefrontal cortices, but were reduced at the dorsovagal complex (DVC). The concentration of AVP-ir was elevated at the paraventricluar hypothalamic nucleus, LC, and DMPFC, and reduced at the DVC. Finally, GRP and NMB variations, which might influence anxiety states, were limited, although GRP-ir within the LC of suicides was higher than in control subjects, while NMB-ir was reduced at the DVC of suicides. CONCLUSIONS: The data show several neuropeptide changes in relation to suicide, although it is premature to ascribe these outcomes specifically to the suicide act versus depression. Likewise, it is uncertain whether the neuropeptide alterations were etiologically related to suicide/depression or secondary to the depressive state.

Adrenocorticotropic Hormone↗
PubMed2005

Stress, depression, and anhedonia: caveats concerning animal models.

Numerous animal models of depression have been advanced, each having multiple attributes and some limitations. This review provides caveats concerning etiologically valid animal models of depression, focusing on characteristics of the depressive subtype being examined (e.g. typical vs atypical major depression, dysthymia, melancholia), and factors that contribute to the interindividual behavioral variability frequently evident in stressor-related behavioral paradigms. These include the stressor type (processive vs systemic stressors), and characteristics of the stressor (controllability, predictability, ambiguity, chronicity, intermittence), as well as organismic variables (genetic, age, sex), experiential variables (stressor history, early life events) and psychosocial and personality factors that moderate stressor reactivity. Finally, a model of depression is reviewed that evaluates the effects of stressors on hedonic processes, reflected by responding for rewarding brain stimulation. Anhedonia is a fundamental feature of depression, and assessment of stressor-related reductions in the rewarding value of brain stimulation, especially when coupled with other potential symptoms of depression, provides considerable face, construct and predictive validity. Stressful events markedly impact rewarding brain stimulation, and this effect varies across strains of mice differentially reactive to stressors, is modifiable by antidepressant treatments, and allows for analyses of the contribution of different brain regions to anhedonic processes. The paradigm is sensitive to several factors known to acts as moderators of stress responses, but analyses remain to be conducted with regard to several such variables.

Age Factors↗
PubMed2005

Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress.

Mutations of the DJ-1 (PARK7) gene are linked to familial Parkinson's disease. We used gene targeting to generate DJ-1-deficient mice that were viable, fertile, and showed no gross anatomical or neuronal abnormalities. Dopaminergic neuron numbers in the substantia nigra and fiber densities and dopamine levels in the striatum were normal. However, DJ-1-/- mice showed hypolocomotion when subjected to amphetamine challenge and increased striatal denervation and dopaminergic neuron loss induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine. DJ-1-/-embryonic cortical neurons showed increased sensitivity to oxidative, but not nonoxidative, insults. Restoration of DJ-1 expression to DJ-1-/- mice or cells via adenoviral vector delivery mitigated all phenotypes. WT mice that received adenoviral delivery of DJ-1 resisted 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine-induced striatal damage, and neurons overexpressing DJ-1 were protected from oxidative stress in vitro. Thus, DJ-1 protects against neuronal oxidative stress, and loss of DJ-1 may lead to Parkinson's disease by conferring hypersensitivity to dopaminergic insults.

Animals↗
PubMed2005

Coping with employment uncertainty: a comparison of employed and unemployed workers.

This study examined coping with stress associated with employment uncertainty for comparable samples of laid-off and employed high-technology workers. It was expected that different coping strategies would be associated with perceived stress for employed vs. unemployed people. Although unemployed participants reported higher levels of stress compared with employed participants, employment uncertainty mediated the association between employment status and perceived stress. Emotion-focused coping strategies were related to higher perceived stress, whereas problem-focused coping strategies were related to lower perceived stress. The use of emotional avoidance as a strategy moderated the effect of employment uncertainty on perceived stress, such that a greater propensity to endorse avoidance coping strategies was associated with higher levels of stress particularly under low uncertainty conditions.

Adaptation, Psychological↗
PubMed2005

The effects of cortisol administration on social status and brain monoaminergic activity in rainbow trout Oncorhynchus mykiss.

The hypothesis that circulating cortisol levels influence the outcome of social interactions in rainbow trout was tested. Juvenile rainbow trout Oncorhynchus mykiss were given a single intraperitoneal (i.p.) implant containing either cortisol (110 mg kg(-1) fish), or cortisol plus the glucocorticoid receptor antagonist RU486 (mifepristone; 1100 mg kg(-1) fish), and sampled after 5 days of social interactions with either a similar sized (<1.5% difference in fork length) or smaller conspecific (>5% difference). Within size-matched pairs of fish, cortisol treatment significantly increased the probability that the treated fish within each pair became subordinate, an effect that was abolished by simultaneous administration of RU486. Cortisol treatment also reduced the usual success of the larger fish within a pair to preferentially become dominant from 86% to 40% of pairs. To investigate one potential mechanism underlying the apparent effect of cortisol in predisposing trout to low social status, fish were treated with cortisol or cortisol+RU486 for 5 days, after which brain monoamines [5-hydroxytryptamine (5-HT); dopamine (DA)] and their major metabolites [5-hydroxyindolacetic acid (5-HIAA); 3,4-dihydroxy-phenylacetic acid (DOPAC)] were measured. Significant increases of serotonergic activity ([5-HIAA]/[5-HT] ratio) were detected in the telencephalon with cortisol treatment, an effect that was eliminated by simultaneous administration of RU486. Also, cortisol treatment significantly decreased dopaminergic activity in the telencephalon. Somewhat surprisingly, the effects of cortisol treatment on monoaminergic activity in the hypothalamus were opposite to those in the telencephalon. Moreover, in no case did administration of RU486 abolish these effects. These results suggest that the effects of cortisol on social status in rainbow trout may be mediated via the modulation of central signaling systems and subsequent changes in behaviour and/or competitive ability, although the exact site of action in the brain remains uncertain.

Analysis of Variance↗
PubMed2005

Parental bonding and depressive affect: the mediating role of coping resources.

Ordinarily, when stressors are encountered, a cascade of cognitive and behavioural responses is evoked that serves to protect the individual from compromised well-being. When coping resources or skills are limited or ineffective, then psychological disturbances, such as depression, may ensue (Paykel, 2001). Although any number of factors could account for variations of stress resilience, this paper argues that early life experiences and relationships, and particularly those with parents or primary caregivers, may contribute to the development of appropriate styles of coping, which, in turn, influence affective responses in the face of stressors encountered in adulthood.

Adaptation, Psychological↗
PubMed2005

Multiple mechanisms of cytokine action in neurodegenerative and psychiatric states: neurochemical and molecular substrates.

Neuroinflammatory processes appear to play a fundamental role in the pathology associated with a number of neurodegenerative and psychiatric conditions. In this respect, the immunocompetent brain microglia and peripheral macrophages release a host of proinflammatory cytokines that not only modulate immunological processes but also influence neuronal functioning and even survival. For instance, alterations of the cytokines, tumor necrosis factor-alpha, as well as several of the interferons and interleukins have been associated with Parkinson's disease (PD) and clinical depression. Importantly, anti-inflammatory treatments that block these cytokines may impart protection against behavioural pathology and neuronal damage in animal models of PD and depression involving exposure to environmental toxins and stressors, respectively. The present review highlights the involvement of inflammatory cells and cytokines in depression and PD and explores some of the potential cellular and molecular mechanisms through which the immunotransmitters affect neuronal functioning. Attention is also devoted to the possibility that cytokines may sensitize neuroinflammatory pathways that, in turn, favour long-term pathology.

Animals↗
PubMed2005

Cytokines as a precipitant of depressive illness: animal and human studies.

Cytokines whose primary function is that of acting as signaling molecules of the immune system, have been implicated in the provocation or exacerbation of mood disorders such as depression. This position has been supported by several lines of evidence; (1) proinflammatory cytokines (interleukin-1beta, interleukin-6, tumor necrosis factor-alpha) and bacterial endotoxins elicit sickness behaviors (e.g., fatigue, soporific effects) and symptoms of anxiety/depression that may be attenuated by chronic antidepressant treatment. Interleukin-2 (IL-2) induces less profound sickness, but elicits anhedonia, a key symptom of depression; (2) neuroendocrine and central neurotransmitter changes, reminiscent of those implicated in depression, may be elicited by some of these cytokines, and these effects are exacerbated by stressors; (3) severe depressive illness is accompanied by elevations of cytokine production or levels, although these effects are not necessarily attenuated with antidepressant medication; and (4) immunotherapy, using IL-2 or IFN-alpha, promote depressive symptoms that are attenuated by antidepressant treatment. It is proposed that chronic cytokine elevations engender neuroendocrine and brain neurotransmitter changes that are interpreted by the brain as being stressors, and contribute to the development of depression. Further, the effects of the cytokine treatments may act synergistically with stressors, and cytokines may provoke a sensitization effect so that the effects of later stressor experiences are exacerbated.

Affect↗
PubMed2004

Regulation of dopaminergic loss by Fas in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease.

Accumulating evidence suggests that apoptotic and inflammatory factors contribute to the demise of dopaminergic neurons. In this respect, Fas, a member of the tumor necrosis factor receptor family with proapoptotic and inflammatory functions, was reported to be elevated within the striatum and substantia nigra pars compacta (SNc) of Parkinson's disease (PD) patients. Accordingly, the present investigation evaluated the function of Fas in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. Injection of MPTP increased nigral Fas expression, and mice lacking Fas displayed attenuated MPTP-induced SNc dopaminergic loss and microglial activation. In addition, Fas induction was blocked by expression of a dominant-negative c-Jun adenovirus that also protected dopamine neurons from MPTP-induced damage. Together, these data suggest the critical nature of the c-Jun-Fas signaling pathway in MPTP-induced neuronal loss. Although critical for degeneration of the soma, Fas deficiency did not significantly prevent the reduction of dopaminergic terminal fibers within the striatum or normalize the activation of striatal microglia and elevation of the postsynaptic activity marker DeltaFosB induced by denervation. Interestingly, Fas-deficient mice displayed a pre-existing reduction in striatal dopamine levels and locomotor behavior when compared with wild-type mice. Despite the reduced terminals, dopamine levels were not further suppressed by MPTP treatment in mutant mice, raising the possibility of a compensatory response in basal ganglia function in Fas-deficient mice.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2004

Dysregulation in the suicide brain: mRNA expression of corticotropin-releasing hormone receptors and GABA(A) receptor subunits in frontal cortical brain region.

Corticotropin-releasing hormone (CRH) and GABA have been implicated in depression, and there is reason to believe that GABA may influence CRH functioning. The levels of CRH, and mRNA for CRH-binding protein, CRH1, and CRH2 receptors, as well as various GABA(A) receptor subunits (alpha1, alpha2, alpha3, alpha4, alpha5, delta, and gamma2), were determined in several frontal cortical brain regions of depressed suicide victims and nondepressed individuals who had not died by suicide. Relative to the comparison group, CRH levels were elevated in frontopolar and dorsomedial prefrontal cortex, but not in the ventrolateral prefrontal cortex of suicide victims. Conversely, using quantitative PCR analyses, it was observed that, in frontopolar cortex, mRNA for CRH1, but not CRH2, receptors were reduced in suicide brains, possibly secondary to the high levels of CRH activity. In addition, mRNA of the alpha1, alpha3, alpha4, and delta receptor subunits was reduced in the frontopolar region of suicide victims. Interestingly, a partial analysis of the GABA(A) receptor functional genome revealed high cross-correlations between subunit expression in cortical regions of nondepressed individuals, suggesting a high degree of coordinated gene regulation. However, in suicide brains, this regulation was perturbed, independent of overall subunit abundance. These findings raise the possibility that the CRH and GABA(A) receptor subunit changes, or the disturbed coordination between these GABA(A) receptor subunits, contribute to depression and/or suicidality or are secondary to the illness/distress associated with it.

Brain↗