Reduced cell proliferation in the dentate gyrusis not correlated with the development of learned helplessness

Vollmayr, Barbara; Simonis, C.; Weber, Silja; Gass, Peter; Henn, Fritz A.

doi:10.1016/s0006-3223(03)00527-4

Cited by 208 publications

(149 citation statements)

References 43 publications

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“…In this study, we demonstrate that acute, and chronic, stress suppress hippocampal cell proliferation, consistent with previous reports (12,32,33) and that the antiproliferative effect of stress is blocked by inhibition of IL-1RI. In vitro studies show that suppression of cell proliferation is mediated by direct actions of IL-1␤ on IL-1RI receptors localized on adult hippocampal progenitor cells via a reduction in cell cycling and not increased cell death.…”

Section: Discussionsupporting

confidence: 93%

“…The shock duration, intensity, and ITI were chosen based on previous work (12). For immobilization stress, rats were restrained in a Plexiglas immobilization tube (3.5-inch diameter ϫ 7-inch length) for 45 min, which was based on previous work (32). For acute stress experiments with mice, half of IL-1RI null and WT mice were stressed for 50 min with a combination of restraint stress and rotation stress on an orbital shaker.…”

Section: Methodsmentioning

confidence: 99%

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IL-1β is an essential mediator of the antineurogenic and anhedonic effects of stress

Koo

Duman

2008

Proc. Natl. Acad. Sci. U.S.A.

761

564

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Stress decreases neurogenesis in the adult hippocampus, and blockade of this effect is required for the actions of antidepressants in behavioral models of depression. However, the mechanisms underlying these effects of stress have not been identified. Here, we demonstrate an essential role for the proinflammatory cytokine IL-1␤. Administration of IL-1␤ or acute stress suppressed hippocampal cell proliferation. Blockade of the IL-1␤ receptor, IL-1RI, by using either an inhibitor or IL-1RI null mice blocks the antineurogenic effect of stress and blocks the anhedonic behavior caused by chronic stress exposure. In vivo and in vitro studies demonstrate that hippocampal neural progenitor cells express IL-1RI and that activation of this receptor decreases cell proliferation via the nuclear factor-B signaling pathway. These findings demonstrate that IL-1␤ is a critical mediator of the antineurogenic and depressive-like behavior caused by acute and chronic stress.cytokine ͉ depression ͉ neurogenesis T he profound consequences of stress exposure, defined as disturbances of physiological homeostasis, include a detrimental impact on certain aspects of brain function (1, 2). In particular, uncontrollable stress is a major contributing factor for neuropsychiatric disorders such as major depression and posttraumatic stress disorders (3, 4). Alterations at the cellular level in the hippocampus have been linked to the pathophysiology of stress-related mood disorders (5-7). Many studies demonstrate that stressful experiences suppress hippocampal neurogenesis, which could contribute to the hippocampal atrophy observed in depressed patients (8-10). In contrast, antidepressant treatment increases hippocampal neurogenesis, blocks the antineurogenic effects of stress (11,12), and reduces or even reverses hippocampal atrophy (9, 11). Recent studies demonstrate that new hippocampal neurons are required for the actions of antidepressants in behavioral models of depression and anxiety (13, 14) with some exceptions (15,16).Despite this progress, the mechanisms underlying the antineurogenic and behavioral actions of stress remain ill defined. One possibility is that excessive proinflammatory cytokines, particularly IL-1␤, contribute to the actions of stress. Animal studies demonstrate that exposure to stress increases IL-1␤ in several brain areas, including the hippocampus (17-20), and central administration of IL-1␤ produces several stress-like effects, including activation of the hypothalamic-pituitary-adrenal (HPA) axis (17, 21), inhibition of hippocampal long-term potentiation (22), down-regulation of hippocampal brain-derived neurotrophic factor (23), and impaired hippocampal-dependent contextual fear conditioning (24). In contrast, blockade of the receptor, IL-1RI that mediates the actions of IL-1␤ (25) inhibits these stress-like effects (23, 24) and blocks the antiproliferative effects of INF-␣ in the hippocampus (26).Based on this evidence, the current study was undertaken to test the hypothesis that the antineurogenic and depressiv...

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Section: Discussionsupporting

confidence: 93%

Section: Methodsmentioning

confidence: 99%

IL-1β is an essential mediator of the antineurogenic and anhedonic effects of stress

Koo

Duman

2008

Proc. Natl. Acad. Sci. U.S.A.

761

564

View full text Add to dashboard Cite

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“…This raises the question of the potential involvement of MIF in behaviors that have been reported to be related (even when discrepancies in the literature still exist) to the interaction between these treatments and hippocampal neurogenesis. 27,30,31,44,45 To address this issue, we tested MIF À/À mice for their anxiety-and depression-like behaviors, as well as for their hippocampus-dependent and -independent learning.…”

Section: Discussionmentioning

confidence: 99%

Macrophage migration inhibitory factor is critically involved in basal and fluoxetine-stimulated adult hippocampal cell proliferation and in anxiety, depression, and memory-related behaviors

et al. 2010

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Intensive research is devoted to unravel the neurobiological mechanisms mediating adult hippocampal neurogenesis, its regulation by antidepressants, and its behavioral consequences. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that is expressed in the CNS, where its function is unknown. Here, we show, for the first time, the relevance of MIF expression for adult hippocampal neurogenesis. We identify MIF expression in neurogenic cells (in stem cells, cells undergoing proliferation, and in newly proliferated cells undergoing maturation) in the subgranular zone of the rodent dentate gyrus. A causal function for MIF in cell proliferation was shown using genetic (MIF gene deletion) and pharmacological (treatment with the MIF antagonist Iso-1) approaches. Behaviorally, genetic deletion of MIF resulted in increased anxiety-and depression-like behaviors, as well as of impaired hippocampus-dependent memory. Together, our studies provide evidence supporting a pivotal function for MIF in both basal and antidepressant-stimulated adult hippocampal cell proliferation. Moreover, loss of MIF results in a behavioral phenotype that, to a large extent, corresponds with alterations predicted to arise from reduced hippocampal neurogenesis. These findings underscore MIF as a potentially relevant molecular target for the development of treatments linked to deficits in neurogenesis, as well as to problems related to anxiety, depression, and cognition.

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“…Several studies with contradicting results suggest that these changes occur in the context of broader impairments of cellular plasticity and resilience, rather than in that of a limited neurogenesis model (van der Hart et al 2002;Morcuende et al 2003;Vollmayr et al 2003). …”

Section: Neurotrophic Factorsmentioning

confidence: 99%

Consensus paper of the WFSBP Task Force on Biological Markers: Biological Markers in Depression

Mößner

Mikova

Koutsilieri

et al. 2007

The World Journal of Biological Psychiatry

226

126

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Biological markers for depression are of great interest to aid in elucidating the causes of major depression. We assess currently available biological markers to query their validity for aiding in the diagnosis of major depression. We specifically focus on neurotrophic factors, serotonergic markers, biochemical markers, immunological markers, neuroimaging, neurophysiological findings, and neuropsychological markers. We delineate the most robust biological markers of major depression. These include decreased platelet imipramine binding, decreased 5-HT1A receptor expression, increase of soluble interleukin-2 receptor and interleukin-6 in serum, decreased brain-derived neurotrophic factor in serum, hypocholesterolemia, low blood folate levels, and impaired suppression of the dexamethasone suppression test. To date, however, none of these markers are sufficiently specific to contribute to the diagnosis of major depression. Thus, with regard to new diagnostic manuals such as DSM-V and ICD-11 which are currently assessing whether biological markers may be included in diagnostic criteria, no biological markers for major depression are currently available for inclusion in the diagnostic criteria.

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Reduced cell proliferation in the dentate gyrusis not correlated with the development of learned helplessness

Cited by 208 publications

References 43 publications

IL-1β is an essential mediator of the antineurogenic and anhedonic effects of stress

IL-1β is an essential mediator of the antineurogenic and anhedonic effects of stress

Macrophage migration inhibitory factor is critically involved in basal and fluoxetine-stimulated adult hippocampal cell proliferation and in anxiety, depression, and memory-related behaviors

Consensus paper of the WFSBP Task Force on Biological Markers: Biological Markers in Depression

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