Repeated Stress Induces Dendritic Spine Loss in the Rat Medial Prefrontal Cortex

Radley, Jason J.; Rocher, Anne B.; Miller, Melinda M.; Janssen, William G.M.; Liston, Conor; Hof, Patrick R.; McEwen, Bruce S.; Morrison, John H.

doi:10.1093/cercor/bhi104

Cited by 707 publications

(607 citation statements)

References 50 publications

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“…Parallel to the findings in the dentate gyrus, the PFC is now receiving increasing attention in preclinical research, especially because the involvement of this brain region in mood disorders is well documented (Drevets, 2000). Recent animal experiments show that chronic stress results in altered dendritic morphology, and reduced spine density in the mPFC, as has been shown in the hippocampal CA3 region (Cook and Wellman, 2004;Radley et al, 2004Radley et al, , 2006. Treatment with the synthetic glucocorticoid dexamethasone results in neuronal loss and atrophy in the mPFC as well as in the granule cell layer of the dentate gyrus (Cerqueira et al, 2005).…”

Section: Stress-induced Structural Changes and Their Potential Implicmentioning

confidence: 91%

Chronic Social Stress Inhibits Cell Proliferation in the Adult Medial Prefrontal Cortex: Hemispheric Asymmetry and Reversal by Fluoxetine Treatment

Czéh

Müller-Keuker

Ryguła

et al. 2006

Neuropsychopharmacol

316

221

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Profound neuroplastic changes have been demonstrated in various limbic structures after chronic stress exposure and antidepressant treatment in animal models of mood disorders. Here, we examined in rats the effect of chronic social stress and concomitant antidepressant treatment on cell proliferation in the medial prefrontal cortex (mPFC). We also examined possible hemispheric differences. Animals were subjected to 5 weeks of daily social defeat by an aggressive conspecific and received concomitant, daily, oral fluoxetine (10 mg/kg) during the last 4 weeks. Bromodeoxyuridine (BrdU) labeling and quantitative stereological techniques were used to evaluate the treatment effects on proliferation and survival of newborn cells in limbic structures such as the mPFC and the hippocampal dentate gyrus, in comparison with nonlimbic structures such as the primary motor cortex and the subventricular zone. Phenotypic analysis showed that neurogenesis dominated the dentate gyrus, whereas in the mPFC most newborn cells were glia, with smaller numbers of endothelial cells. Chronic stress significantly suppressed cytogenesis in the mPFC and neurogenesis in the dentate gyrus, but had minor effect in nonlimbic structures. Fluoxetine treatment counteracted the inhibitory effect of stress. Hemispheric comparison revealed that the rate of cytogenesis was significantly higher in the left mPFC of control animals, whereas stress inverted this asymmetry, yielding a significantly higher incidence of newborn cells in the right mPFC. Fluoxetine treatment abolished hemispheric asymmetry in both control and stressed animals. These pronounced changes in gliogenesis after chronic stress exposure may relate to the abnormalities of glial cell numbers reported in the frontolimbic areas of depressed patients.

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Section: Stress-induced Structural Changes and Their Potential Implicmentioning

confidence: 91%

Chronic Social Stress Inhibits Cell Proliferation in the Adult Medial Prefrontal Cortex: Hemispheric Asymmetry and Reversal by Fluoxetine Treatment

Czéh

Müller-Keuker

Ryguła

et al. 2006

Neuropsychopharmacol

316

221

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“…Interestingly, although the expression of PSA-NCAM seems to be exclusive of mPFC interneurons (Varea et al, 2005), all the structural changes reported in the mPFC were only described in pyramidal neurons (Radley et al, 2005). However, at least some of these principal neurons are surrounded by PSA-NCAM immunoreactive puncta that may correspond to synapses (Varea et al, 2005).…”

Section: Involvement Of Psa-ncam Expression In Mpfc Neuronal Structurmentioning

confidence: 97%

Chronic Fluoxetine Treatment Increases the Expression of PSA-NCAM in the Medial Prefrontal Cortex

Varea

Blasco-Ibáñez

Gómez-Climent

et al. 2006

Neuropsychopharmacol

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Recent hypotheses suggest that changes in neuronal structure and connectivity may underlie the etiology of depression. The medial prefrontal cortex (mPFC) is affected by depression and shows neuronal remodeling during adulthood. This plasticity may be mediated by the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), which is intensely expressed in the adult mPFC. As the expression of PSA-NCAM is increased by serotonin in other cerebral regions, antidepressants acting on serotonin reuptake may influence PSA-NCAM expression and thus counteract the effects of depression by modulating neuronal structural plasticity. Using immunohistochemistry, we have studied the relationship between serotoninergic fibers and PSA-NCAM expressing neurons in the adult rat mPFC and the expression of serotonin receptors in these cells. The effects of fluoxetine treatment for 14 days on mPFC PSA-NCAM expression have also been analyzed. Although serotoninergic fibers usually do not contact PSA-NCAM immunoreactive neurons, most of these cells express 5-HT3 receptors. In general, chronic fluoxetine treatment induces significant increases in the number of PSA-NCAM immunoreactive neurons and in neuropil immunostaining and coadministration of the 5-HT3 antagonist ondansetron blocks the effects of fluoxetine on PSA-NCAM expression. These results indicate that fluoxetine, acting through 5-HT3 receptors, can modulate PSA-NCAM expression in the mPFC. This modulation may mediate the structural plasticity of this cortical region and opens new perspectives on the study of the molecular bases of depression.

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“…However, when the level of hormones remains elevated for a long period of time, the central nervous system can be cumulatively damaged by the exposure [10,16]. For instance, chronically elevated levels of cortisol can impair the development of the prefrontal cortex (PFC) [14], which has a large density of glucocorticoid receptors [17], causing dendrite retraction and a decline in the number of dendritic spines; both effects leading to an overall decrease in synaptic contacts [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Effect of chronic stress during adolescence in prefrontal cortex structure and function

Folha

Bahia

Aguiar

et al. 2017

Behavioural Brain Research

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h i g h l i g h t s• Chronic stress impairs the development of the adolescent brain.• Chronic stress delays the maturation of extracellular structures called perineuronal nets, which stabilize synaptic contacts on inhibitory neurons, and prefrontal cortex-associated behavior.• These negative effects of chronic stress on the prefrontal cortex can theoretically occur in humans. Critical periods of plasticity (CPPs) are defined by developmental intervals wherein neuronal circuits are most susceptible to environmental influences. The CPP of the prefrontal cortex (PFC), which controls executive functions, extends up to early adulthood and, like other cortical areas, reflects the maturation of perineuronal nets (PNNs) surrounding the cell bodies of specialized inhibitory interneurons. The aim of the present work was to evaluate the effect of chronic stress on both structure and function of the adolescent's rat PFC. We subjected P28 rats to stressful situations for 7, 15 and 35 days and evaluated the spatial distribution of histochemically-labeled PNNs in both the Medial Prefrontal Cortex (MPFC) and the Orbitofrontal Cortex (OFC) and PFC-associated behavior as well. Chronic stress affects PFC development, slowing PNN maturation in both the (MPFC) and (OFC) while negatively affecting functions associated with these areas. We speculate upon the risks of prolonged exposure to stressful environments in human adolescents and the possibility of stunted development of executive functions.

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Repeated Stress Induces Dendritic Spine Loss in the Rat Medial Prefrontal Cortex

Cited by 707 publications

References 50 publications

Chronic Social Stress Inhibits Cell Proliferation in the Adult Medial Prefrontal Cortex: Hemispheric Asymmetry and Reversal by Fluoxetine Treatment

Chronic Social Stress Inhibits Cell Proliferation in the Adult Medial Prefrontal Cortex: Hemispheric Asymmetry and Reversal by Fluoxetine Treatment

Chronic Fluoxetine Treatment Increases the Expression of PSA-NCAM in the Medial Prefrontal Cortex

Effect of chronic stress during adolescence in prefrontal cortex structure and function

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