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

CONBOY, L ; VAREA, E ; CASTRO, J. E ; SAKOUHI-OUERTATANI, H ; CALANDRA, T ; LASHUEL, H. A ; SANDI, C

Molecular psychiatry, 2011-05, Vol.16 (5), p.533-547 [Periódico revisado por pares]

Basingstoke: Nature Publishing Group

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Macrophage migration inhibitory factor is critically involved in basal and fluoxetine-stimulated adult hippocampal cell proliferation and in anxiety, depression, and memory-related behaviors
Autor: CONBOY, L ; VAREA, E ; CASTRO, J. E ; SAKOUHI-OUERTATANI, H ; CALANDRA, T ; LASHUEL, H. A ; SANDI, C
Assuntos: Acoustic Stimulation - adverse effects ; Adult and adolescent clinical studies ; Animals ; Antidepressants ; Antidepressive Agents, Second-Generation - pharmacology ; Antidepressive Agents, Second-Generation - therapeutic use ; Anxiety ; Anxiety - drug therapy ; Anxiety - genetics ; Anxiety - pathology ; Behavior ; Biological and medical sciences ; Bromodeoxyuridine - metabolism ; C-Reactive Protein - drug effects ; C-Reactive Protein - metabolism ; Cell growth ; Cell proliferation ; Cell Proliferation - drug effects ; Cognition ; Conditioning (Psychology) - drug effects ; Corticosterone - blood ; Corticosterone - therapeutic use ; Cytokines ; Dentate gyrus ; Depression ; Depression - drug therapy ; Depression - genetics ; Depression - pathology ; Disease Models, Animal ; Fear ; Fluoxetine ; Fluoxetine - pharmacology ; Fluoxetine - therapeutic use ; Gene deletion ; Health aspects ; Hippocampus ; Hippocampus - drug effects ; Hippocampus - pathology ; Inflammation ; Leukocyte migration ; Macrophage migration inhibitory factor ; Macrophage Migration-Inhibitory Factors - deficiency ; Macrophage Migration-Inhibitory Factors - metabolism ; Macrophages ; Maze Learning - drug effects ; Maze Learning - physiology ; Medical sciences ; Memory ; Memory Disorders - drug therapy ; Memory Disorders - genetics ; Memory Disorders - pathology ; Mental depression ; Mental illness ; Mice ; Mice, Knockout ; Microscopy, Confocal - methods ; Mood disorders ; Nerve Tissue Proteins - drug effects ; Nerve Tissue Proteins - metabolism ; Neurogenesis ; Neurogenesis - drug effects ; Neuropharmacology ; Pharmacology. Drug treatments ; Phenotypes ; Physiological aspects ; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer ; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Psychopharmacology ; Rats ; Rats, Wistar ; Receptors, Steroid - metabolism ; Risk factors ; Spatial Behavior - drug effects ; Stem cell transplantation ; Stem cells
É parte de: Molecular psychiatry, 2011-05, Vol.16 (5), p.533-547
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Descrição: 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.
Editor: Basingstoke: Nature Publishing Group
Idioma: Inglês

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

CONBOY, L ; VAREA, E ; CASTRO, J. E ; SAKOUHI-OUERTATANI, H ; CALANDRA, T ; LASHUEL, H. A ; SANDI, C

Basingstoke: Nature Publishing Group

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