Stereological assessment of the dorsal anterior cingulate cortex in schizophrenia: absence of changes in neuronal and glial densities
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M. Höistad, H. Heinsen, B. Wicinski, C. Schmitz and P. R. Hof (2013) Neuropathology and Applied Neurobiology 39, 348–361 Stereological assessment of the dorsal anterior cingulate cortex in schizophrenia: absence of changes in neuronal and glial densities Aims: The prefrontal and anterior cingulate cortices are implicated in schizophrenia, and many studies have assessed volume, cortical thickness, and neuronal densities or numbers in these regions. Available data, however, are rather conflicting and no clear cortical alteration pattern has been established. Changes in oligodendrocytes and white matter have been observed in schizophrenia, introducing a hypothesis about a myelin deficit as a key event in disease development. Methods: We investigated the dorsal anterior cingulate cortex (dACC) in 13 men with schizophrenia and 13 age‐ and gender‐matched controls. We assessed stereologically the dACC volume, neuronal and glial densities, total neurone and glial numbers, and glia/neurone index (GNI) in both layers II–III and V–VI. Results: We observed no differences in neuronal or glial densities. No changes were observed in dACC cortical volume, total neurone numbers, and total glial numbers in schizophrenia. This contrasts with previous findings and suggests that the dACC may not undergo as severe changes in schizophrenia as is generally believed. However, we observed higher glial densities in layers V–VI than in layers II–III in both controls and patients with schizophrenia, pointing to possible layer‐specific effects on oligodendrocyte distribution during development. Conclusions: Using rigorous stereological methods, we demonstrate a seemingly normal cortical organization in an important neocortical area for schizophrenia, emphasizing the importance of such morphometric approaches in quantitative neuropathology. We discuss the significance of subregion‐ and layer‐specific alterations in the development of schizophrenia, and the discrepancies between post mortem histopathological studies and in vivo brain imaging findings in patients.Keywords:
Cingulate cortex
Stereology
Cingulate cortex
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Background The enhanced expression of cytokines in the pathological states suggests that they have important roles in the initiation or maintenance of disease states. Findings: To determine the involvement of cytokines in chronic neuropathic pain, the expression of cytokines in the anterior cingulate cortex neurons in the ligation of the common peroneal nerve mice was investigated. We utilized a cytokine enzyme-linked immunosorbent assay plate array to detect 23 cytokines in total eight mice including a female, and no significant differences were found in those cytokines between the common peroneal nerve model and sham surgery mice. Quantification of TNF-α at protein level revealed the unvaried expression in the anterior cingulate cortex in both neuropathic pain and visceral pain, but enhanced expression in the insular cortex in the visceral pain. Furthermore, we found that the IL-Ira, a kind of IL-1 receptor antagonist, had no effect on the theta burst stimulation-induced long-term potentiation in the anterior cingulate cortex. Conclusions Cytokines are not involved in chronic neuropathic pain induced by nerve injury in the anterior cingulate cortex. Our findings suggested that cytokines may not be a viable drug target to treat chronic neuropathic pain in the anterior cingulate cortex.
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Studies in animals suggest that the limbic prefrontal cortex, including the anterior cingulate cortex, is involved in regulation of the hypothalamic-pituitary-adrenal (HPA) axis, but human data are lacking.This study tested the hypothesis that smaller anterior cingulate cortex volumes are associated with HPA axis dysregulation in healthy older men.Comparison was made of volumes of bilateral anterior cingulate cortex, hippocampus, and superior frontal gyrus (control region) volumes in two groups of 10 healthy men, aged 65-70 yr, who showed nonsuppression or suppression of cortisol levels in response to low dose (250 microg) dexamethasone. Analysis of brain volumes was performed blind to the cortisol levels.This study was performed at a tertiary care clinical research center.Nonsuppressors had significantly smaller left anterior cingulate cortex volumes than suppressors (5757 vs. 7817 mm(3); P = 0.01). Right anterior cingulate cortex, bilateral hippocampus, and bilateral superior frontal gyrus volumes were not significantly different between nonsuppressors and suppressors.Smaller left anterior cingulate cortex volumes may be associated with HPA axis dysregulation in humans. These results substantiate evidence from animal studies indicating an important role for the anterior cingulate cortex in suprahypothalamic feedback regulation of the HPA axis. The results also have implications for disorders in which HPA axis dysregulation and abnormalities of the anterior cingulate cortex are frequently observed, such as depression and Alzheimer's disease.
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Limbic lobe
Limbic system
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Anterior cingulate cortex (ACC), an important part of the limbic system, has extensive connections with other cortical areas and subcortical nuclei and is involved in modulating many functions. In recent years, an increasing body of evidence in eletrophysiology, functional imaging and behavioral study indicates that ACC is closely involved in processing of pain, especially in the affective dimension of pain. This review will focus on the progress in the study of ACC in processing of pain.
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Reward and punishment have opposite affective value but are both processed by the cingulate cortex. However, it is unclear whether the positive and negative affective values of monetary reward and punishment are processed by separate or common subregions of the cingulate cortex. We performed a functional magnetic resonance imaging study using a free-choice task and compared cingulate activations for different levels of monetary gain and loss. Gain-specific activation (increasing activation for increasing gain, but no activation change in relation to loss) occurred mainly in the anterior part of the anterior cingulate and in the posterior cingulate cortex. Conversely, loss-specific activation (increasing activation for increasing loss, but no activation change in relation to gain) occurred between these areas, in the middle and posterior part of the anterior cingulate. Integrated coding of gain and loss (increasing activation throughout the full range, from biggest loss to biggest gain) occurred in the dorsal part of the anterior cingulate, at the border with the medial prefrontal cortex. Finally, unspecific activation increases to both gains and losses (increasing activation to increasing gains and increasing losses, possibly reflecting attention) occurred in dorsal and middle regions of the cingulate cortex. Together, these results suggest separate and common coding of monetary reward and punishment in distinct subregions of the cingulate cortex. Further meta-analysis suggested that the presently found reward- and punishment-specific areas overlapped with those processing positive and negative emotions, respectively.
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The role of the cingulate cortex in regulating male sexual behavior was studied in testosterone propionate-treated castrated male rats.Males with lesions in the anterior part of the cingulate cortex showed lower levels of mount, intromission and ejaculation activities than shamoperated control males and males with lesions in the posterior part of the cingulate cortex or the frontal cortex.In male rats in which lateral connections of the anterior cingulate cortex were bilaterally interrupted by sagittal cuts, the sexual activity was much lower than in the control rats, being comparable to that of the anterior cingulate cortex lesion group, but transection of the anterior connections by a transverse cut made in the anterior part of the anterior cingulate had no effect.These results suggest that the anterior cingulate cortex and its lateral connections are critical in regulating male sexual behavior in male rats.
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