Transcriptomic Landscape of von Economo Neurons in Human Anterior Cingulate Cortex Revealed by Microdissected-Cell RNA Sequencing

Abstract Background: Neuropathic pain is a troublesome pathological condition without suitable treatments. Anterior Cingulate Cortex (ACC) is a core brain region to process pain emotion. In this study, we performed RNA sequencing analysis to reveal transcriptomic profiles of the ACC in a rat chronic constriction injury (CCI) model.Results: A total of 1628 differentially expressed genes (DEGs) were identified by comparing the sham-operated rats and rats of 12 hours, 1, 3, 7 and 14 days after surgery, respectively. Most of the DEGs were involved in inflammatory and immune process. Although these inflammatory-related DEGs were generally increased after CCI, they demonstrated different kinetics in time-series expression with the development of neuropathic pain affection. Specifically, the expression of Ccl5 , Cxcl9 and Cxcl13 were kept going up after CCI, indicating a potentially effect of these genes on initiation and maintenance of neuropathic pain affection. The expression of Ccl2 , Ccl3 , Ccl4 , Ccl6 and Ccl7 were initially upregulated at 12 hours after CCI and then they fell back after that. Similarly, the expression of Rac2 , Cd68 , Icam-1 , Ptprc , Itgb2 , Fcgr2b were rised at 12 hours and 1 day, but fell back at 3 days after CCI. However, the expression of all of the above two clusters of genes were increased again at 7 days after CCI, when the neuropathic pain affection was developed. The initial increase of these genes may indicate an early response of ACC to nerve injury, whereas the later increase of these genes may indicate their involvement in the developing of neuropathic pain affection. Gene Ontology analysis, KEGG pathway enrichment and interaction network analysis further showed a high connectivity degree among these chemokine targeting genes. Similar expressional changes of these genes were also found in the rat spinal dorsal taking charge of the processing of nociception.Conclusions: Our results indicate chemokines and their targeting genes in ACC may be differentially involved in the initiation and maintenance of neuropathic pain affection. These genes could be the target not only the nociception but also the pain affection subsequent to nerve injury.

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The von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans

Brain Structure and Function ◽

10.1007/s00429-010-0254-0 ◽

2010 ◽

Vol 214 (5-6) ◽

pp. 495-517 ◽

Cited By ~ 212

Author(s):

John M. Allman ◽

Nicole A. Tetreault ◽

Atiya Y. Hakeem ◽

Kebreten F. Manaye ◽

Katerina Semendeferi ◽

...

Keyword(s):

Anterior Cingulate Cortex ◽

Cingulate Cortex ◽

Great Apes ◽

Anterior Cingulate ◽

Von Economo Neurons

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Circular RNA circCCNT2 is upregulated in the anterior cingulate cortex of individuals with bipolar disorder

Translational Psychiatry ◽

10.1038/s41398-021-01746-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Rixing Lin ◽

Juan Pablo Lopez ◽

Cristiana Cruceanu ◽

Caroline Pierotti ◽

Laura M. Fiori ◽

...

Keyword(s):

Bipolar Disorder ◽

Anterior Cingulate Cortex ◽

Rna Sequencing ◽

Lithium Treatment ◽

Cingulate Cortex ◽

Anterior Cingulate ◽

Circular Rnas ◽

Sequencing Analysis ◽

The Brain

AbstractGene expression dysregulation in the brain has been associated with bipolar disorder, but little is known about the role of non-coding RNAs. Circular RNAs are a novel class of long noncoding RNAs that have recently been shown to be important in brain development and function. However, their potential role in psychiatric disorders, including bipolar disorder, has not been well investigated. In this study, we profiled circular RNAs in the brain tissue of individuals with bipolar disorder. Total RNA sequencing was initially performed in samples from the anterior cingulate cortex of a cohort comprised of individuals with bipolar disorder (N = 13) and neurotypical controls (N = 13) and circular RNAs were identified and analyzed using “circtools”. Significant circular RNAs were validated by RT-qPCR and replicated in the anterior cingulate cortex in an independent cohort (24 bipolar disorder cases and 27 controls). In addition, we conducted in vitro studies using B-lymphoblastoid cells collected from bipolar cases (N = 19) and healthy controls (N = 12) to investigate how circular RNAs respond following lithium treatment. In the discovery RNA sequencing analysis, 26 circular RNAs were significantly differentially expressed between bipolar disorder cases and controls (FDR < 0.1). Of these, circCCNT2 was RT-qPCR validated showing significant upregulation in bipolar disorder (p = 0.03). This upregulation in bipolar disorder was replicated in an independent post-mortem human anterior cingulate cortex cohort and in B-lymphoblastoid cell culture. Furthermore, circCCNT2 expression was reduced in response to lithium treatment in vitro. Together, our study is the first to associate circCCNT2 to bipolar disorder and lithium treatment.

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The behavioral variant of Alzheimer's disease does not show a selective loss of Von Economo and phylogenetically related neurons in the anterior cingulate cortex

10.1101/2021.10.30.21265649 ◽

2021 ◽

Author(s):

Ellen Singleton ◽

Yolande A.L. Pijnenburg ◽

Priya Gami-Patel ◽

Baayla D.C. Boon ◽

Femke Bouwman ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Anterior Cingulate Cortex ◽

Pyramidal Neurons ◽

Neuronal Loss ◽

Cingulate Cortex ◽

Anterior Cingulate ◽

Von Economo Neurons ◽

Neuronal Populations ◽

Selective Loss

Background: The neurobiological origins of the early and predominant behavioral changes seen in the behavioral variant of Alzheimer's disease (bvAD) remain unclear. A selective loss of Von Economo Neurons (VENs) and phylogenetically related neurons have been observed in behavioral variant frontotemporal dementia (bvFTD) and several psychiatric diseases. Here, we assessed whether these specific neuronal populations show a selective loss in bvAD. Methods: VENs and GABA receptor subunit theta (GABRQ)-immunoreactive pyramidal neurons of the anterior cingulate cortex (ACC) were quantified in post-mortem tissue of patients with bvAD (n=9) and compared to typical AD (tAD, n=6), bvFTD due to frontotemporal lobar degeneration based on TDP-43 pathology (FTLD, n=18) and controls (n=13) using ANCOVAs adjusted for age and Bonferroni corrected. In addition, ratios of VENs and GABRQ-immunoreactive (GABRQ-ir) pyramidal neurons over all Layer 5 neurons were compared between groups to correct for overall Layer 5 neuronal loss. Results: The number of VENs or GABRQ-ir neurons did not differ significantly between bvAD (VENs: 26.0±15.3, GABRQ-ir pyramidal: 260.44±87.13) and tAD (VENs: 32.0±18.1, p=1.00, GABRQ-ir pyramidal: 349.83±109.64, p=0.38) and controls (VENs: 33.5±20.3, p=1.00, GABRQ-ir pyramidal: 339.38±95.88, p=0.37). Compared to bvFTD, patients with bvAD showed significantly more GABRQ-ir pyramidal neurons (bvFTD: 140.39±82.58, p=0.01) and no significant differences in number of VENs (bvFTD: 10.9±13.8, p=0.13). Results were similar when assessing the number of VENs and GABRQ-ir relative to all neurons of Layer 5. Discussion: VENs and phylogenetically related neurons did not show a selective loss in the ACC in patients with bvAD. Our results suggest that, unlike in bvFTD, the clinical presentation in bvAD may not be related to the loss of VENs and related neurons in the ACC.

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