Dendritic Spine Density in Schizophrenia and Depression

Glantz, Leisa A.

doi:10.1001/archpsyc.58.2.203

Cited by 65 publications

(40 citation statements)

References 2 publications

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“…This view is consistent with ongoing debate over the cause of MRI-based grey matter reductions (Weinberger and McClure, 2002;Mathalon et al 2003), and evidence that such reductions may not necessarily result from a unitary process (Fornito et al, 2009). For example, reductions in neuron density have commonly been found in post-mortem studies of medial temporal, medial prefrontal and thalamic regions in schizophrenic patients (Todtenkopf et al, 2005), whereas increased neuronal density, accompanied by reduced synaptic density, has been a replicated finding in lateral prefrontal areas (Glantz and Lewis, 2001). …”

Section: Discussionsupporting

confidence: 71%

Stereological Evaluation of Brain Magnetic Resonance Images of Schizophrenic Patients

Elfaki

Osman

et al. 2013

Image Anal Stereol

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Advances in neuroimaging have enabled studies of specific neuroanatomical abnormalities with relevance to schizophrenia. This study quantified structural alterations on brain magnetic resonance (MR) images of patients with schizophrenia. MR brain imaging was done on 88 control and 57 schizophrenic subjects and Dicom images were analyzed with ImageJ software. The brain volume was estimated with the planimetric stereological technique. The volume fraction of brain structures was also estimated. The results showed that, the mean volume of right, left, and total hemispheres in controls were 551, 550, and 1101 cm 3 , respectively. The mean volumes of right, left, and total hemispheres in schizophrenics were 513, 512, and 1026 cm 3 , respectively. The schizophrenics' brains were smaller than the controls (p < 0.05). The mean volume of total white matter of controls (516 cm 3 ) was bigger than the schizophrenics' volume (451 cm 3 ), (p < 0.05). The volume fraction of total white matter was also lower in schizophrenics (p < 0.05). Volume fraction of the lateral ventricles was higher in schizophrenics (p < 0.05). According to the findings, the volumes of schizophrenics' brain were smaller than the controls and the volume fractional changes in schizophrenics showed sex dependent differences. We conclude that stereological analysis of MR brain images is useful for quantifying schizophrenia related structural changes.

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Section: Discussionsupporting

confidence: 71%

Stereological Evaluation of Brain Magnetic Resonance Images of Schizophrenic Patients

Elfaki

Osman

et al. 2013

Image Anal Stereol

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“…Although we cannot conclude that the loss of spines causes cognitive changes, these findings suggest that protecting prefrontal regions vulnerable to stress may be key to rescuing prefrontal cortical regulation of behavior and cognition. These findings may encourage postmortem spine-counting studies, similar to the rigorous anatomical analyses performed by Glantz and colleagues (36,46), examining spine pathology in the prefrontal cortex of patients with bipolar disorder, PTSD, and lead poisoning.…”

Section: Discussionmentioning

confidence: 66%

Inhibition of protein kinase C signaling protects prefrontal cortex dendritic spines and cognition from the effects of chronic stress

Hains

Maciejewski

et al. 2009

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

200

186

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The prefrontal cortex r regulates behavior, cognition, and emotion by using working memory. Prefrontal functions are impaired by stress exposure. Acute, stress-induced deficits arise from excessive protein kinase C (PKC) signaling, which diminishes prefrontal neuronal firing. Chronic stress additionally produces architectural changes, reducing dendritic complexity and spine density of cortico-cortical pyramidal neurons, thereby disrupting excitatory working memory networks. In vitro studies have found that sustained PKC activity leads to spine loss from hippocampalcultured neurons, suggesting that PKC may contribute to spine loss during chronic stress exposure. The present study tested whether inhibition of PKC with chelerythrine before daily stress would protect prefrontal spines and working memory. We found that inhibition of PKC rescued working memory impairments and reversed distal apical dendritic spine loss in layer II/III pyramidal neurons of rat prelimbic cortex. Greater spine density predicted better cognitive performance, the first direct correlation between pyramidal cell structure and working memory abilities. These findings suggest that PKC inhibitors may be neuroprotective in disorders with dysregulated PKC signaling such as bipolar disorder, schizophrenia, post-traumatic stress disorder, and lead poisoning-conditions characterized by impoverished prefrontal structural and functional integrity. bipolar disorder ͉ post-traumatic stress disorder ͉ working memory ͉ chelerythrine ͉ lead poisoning

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“…Neurotrophins, acting through trk receptors, can regulate such varied processes as glutamate and GABA neuronal survival, neuronal excitability, somal size, axonal arborization, dendritic architecture, synaptic protein levels and spine density. Morphological and molecular abnormalities of neurons in the DLPFC in schizophrenics include: (1) subtle reductions in somal size, 43,44 (2) reductions in spine density, predominantly in layer III, 45,46 (3) increased neuronal density in the superficial layers II and III 47,48 and (4) reductions in some, but not all, mRNAs and proteins associated with presynaptic terminals. 35,[49][50][51] Our evidence of diminished neurotrophic signaling capabilities in patients with schizophrenia is consistent with these pathological changes.…”

Section: Discussionmentioning

confidence: 99%

Reductions in neurotrophin receptor mRNAs in the prefrontal cortex of patients with schizophrenia

et al. 2005

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Patients with schizophrenia have reduced neurotrophin levels in their dorsolateral prefrontal cortex (DLPFC) compared to normal unaffected individuals. The tyrosine kinase-containing receptors, trkB and trkC, mediate the growth-promoting effects of neurotrophins and respond to changes in growth factor availability. We hypothesized that trkB and/or trkC expression would be altered in the DLPFC of patients with schizophrenia. We measured mRNA encoding the tyrosine kinase domain (TK þ )-containing form of trkB and measured pan trkC mRNA in schizophrenics (N ¼ 14) and controls (N ¼ 15) using in situ hybridization. TrkB and trkC mRNAs were detected in large and small neurons in multiple cortical layers of the human DLPFC. We found significantly diminished expression of trkB TK þ mRNA in large neurons in multiple cortical layers of patients as compared to controls, while small neurons also showed reductions in trkB TK þ mRNA that did not reach statistical significance. In normals, strong positive correlations were found between trkB TK þ mRNA levels and brain-derived neurotrophic factor (BDNF) mRNA levels among various neurons, while no correlation between BDNF and trkB TK þ was found in patients with schizophrenia. TrkC mRNA was also reduced in the DLPFC of schizophrenics in large neurons in layers II, III, V and VI and in small neurons in layer IV. Since neurons in the DLPFC integrate and communicate signals to various cortical and subcortical regions, these reductions in growth factor receptors may compromise the function and plasticity of the DLPFC in schizophrenia. Molecular Psychiatry (2005) 10, 637-650.

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Dendritic Spine Density in Schizophrenia and Depression

Cited by 65 publications

References 2 publications

Stereological Evaluation of Brain Magnetic Resonance Images of Schizophrenic Patients

Stereological Evaluation of Brain Magnetic Resonance Images of Schizophrenic Patients

Inhibition of protein kinase C signaling protects prefrontal cortex dendritic spines and cognition from the effects of chronic stress

Reductions in neurotrophin receptor mRNAs in the prefrontal cortex of patients with schizophrenia

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