Reduced Glial Cell Density and Neuronal Size in the Anterior Cingulate Cortex in Major Depressive Disorder

Cotter, David; Mackay, Daniel; Landau, Sabine; Kerwin, Robert; Everall, Ian

doi:10.1001/archpsyc.58.6.545

Cited by 707 publications

(467 citation statements)

References 66 publications

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“…On the other hand, several postmortem studies on major depression have given opposite findings, namely, prominent decrease in the number and the density of astrocytes in major depression patients compared to age‐matched nonpsychiatric controls. Such a reduction in astrocytic population was observed in the dorsolateral prefrontal (Cotter, Mackay, Landau, Kerwin, & Everall, 2001; Rajkowska et al., 1999), orbitofrontal (Rajkowska et al., 1999), subgenual (Ongur, Drevets, & Price, 1998), and anterior cingulate cortex (Cotter et al., 2001). This discrepancy may stem from a difference in brain regions studied.…”

Section: Discussionmentioning

confidence: 78%

Gunn rats with glial activation in the hippocampus show prolonged immobility time in the forced swimming test and tail suspension test

et al. 2018

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IntroductionRecent studies imply that glial activation plays a role in the pathogenesis of psychiatric disorders, such as schizophrenia and major depression. We previously demonstrated that Gunn rats with hyperbilirubinemia show congenital gliosis and schizophrenia‐like behavior.MethodsAs it has been suggested that major depression involves glial activation associated with neuroinflammation, we examined whether Gunn rats show depression‐like behavior using the forced swimming test (FST) and the tail suspension test (TST). In addition, we quantitatively evaluated both microgliosis and astrogliosis in the hippocampus of Gunn rats using immunohistochemistry analysis of the microglial marker ionized calcium‐binding adaptor molecule (Iba) 1 and the astrocytic marker S100B.ResultsBoth the FST and TST showed that immobility time of Gunn rats was significantly longer than that of normal control Wistar rats, indicating that Gunn rats are somewhat helpless, a sign of depression‐like behavior. In the quantification of immunohistochemical analysis, Iba1immunoreactivity in the dentate gyrus (DG), cornu ammonis (CA) 1, and CA3 and the number of Iba1‐positive cells in the CA1 and CA3 were significantly increased in Gunn rats compared to Wistar rats. S100B immunoreactivity in the DG, CA1, and CA3 and the number of S100B‐positive cells in the DG and CA3 were significantly increased in Gunn rats compared to Wistar rats.ConclusionOur findings suggest that both microglia and astrocyte are activated in Gunn rats and their learned helplessness could be related to glial activation.

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Section: Discussionmentioning

confidence: 78%

Gunn rats with glial activation in the hippocampus show prolonged immobility time in the forced swimming test and tail suspension test

et al. 2018

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“…As stress is associated with the risk of developing depression (Kessler, 1997;Kendler et al, 1999), the morphological findings of preclinical studies, where animals are exposed to chronic stressful experiences, are commonly related to the structural changes reported in the brains of depressed patients. In vivo imaging studies reveal selective volume reduction in the PFC (Drevets, 2000), and post mortem histological data show reductions in neuronal size and glial cell numbers in specific subregions of the frontal cortex in depressed patients (Ö ngür et al, 1998;Rajkowska et al, 1999;Cotter et al, 2001aCotter et al, , 2002Uranova et al, 2004). It is tempting to speculate that our finding on the 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.…”

Section: Stress-induced Structural Changes and Their Potential Implicmentioning

confidence: 76%

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

318

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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“…Post-mortem studies of glial cell pathology in depression have reinforced this concept, although findings remain conflicted in many cases. [43][44][45][46] The observation of a significant misexpression of molecules central to both GABAergic and glutamatergic neurotransmission in the cortical areas of individuals with major depression has been previously documented by several groups. 21,23,47 These studies follow on a body of clinical evidence showing that antidepressant medications may reduce glutamatergic activity while raising cortical GABA levels, which are seen to be reduced in major depression 48,49 and possibly also schizophrenia.…”

Section: Discussionmentioning

confidence: 94%

Altered expression of genes involved in ATP biosynthesis and GABAergic neurotransmission in the ventral prefrontal cortex of suicides with and without major depression

et al. 2007

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The prefrontal cortex is believed to play a major role in depression and suicidal behavior through regulation of cognition, memory, recognition of emotion, and anxiety-like states, with numerous post-mortem studies documenting a prefrontal serotonergic dysregulation considered to be characteristic of depressive psychopathology. This study was carried out to detect changes in gene expression associated with both suicide and major depression using oligonucleotide microarrays (Affymetrix HG-U133 chip set) summarizing expression patterns in primarily ventral regions of the prefrontal cortex (BA44, 45, 46 and 47). A total of 37 male subjects were included in this study, of which 24 were suicides (depressed suicides = 16, nondepressed suicides = 8) and 13 were matched controls. All subjects were clinically characterized by means of psychological autopsies using structured interviews. Unique patterns of differential expression were validated in each of the cortical regions evaluated, with group-specific changes highlighting the involvement of several key neurobiological pathways that have been implicated in both suicide and depression. An overrepresentation of factors involved in cell cycle control and cell division (BA44), transcription (BA44 and 47) and myelination (BA46) was seen in gene ontology analysis of differentially expressed genes, which also highlights changes in the expression of genes involved in ATP biosynthesis and utilization across all areas. Gene misexpression in BA46 was most pronounced between the two suicide groups, with many significant genes involved in GABAergic neurotransmission. The pronounced misexpression of genes central to GABAergic signaling and astrocyte/ oligodendrocyte function provides further support for a central glial pathology in depression and suicidal behavior.

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Reduced Glial Cell Density and Neuronal Size in the Anterior Cingulate Cortex in Major Depressive Disorder

Abstract: These findings suggest that there is reduced frontal cortical glial cell density and neuronal size in major depressive disorder.

Cited by 707 publications

References 66 publications

Gunn rats with glial activation in the hippocampus show prolonged immobility time in the forced swimming test and tail suspension test

Gunn rats with glial activation in the hippocampus show prolonged immobility time in the forced swimming test and tail suspension test

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

Altered expression of genes involved in ATP biosynthesis and GABAergic neurotransmission in the ventral prefrontal cortex of suicides with and without major depression

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