scholarly journals Tcf4 encodescortical differentiation during development

2018 ◽  
Author(s):  
Simone Mesman ◽  
Reinier Bakker ◽  
Marten P. Smidt
Keyword(s):  
Genetic Counseling ◽  
Corpus Callosum ◽  
Human Brain ◽  
Rna Sequencing ◽  
Neurodevelopmental Disorders ◽  
Disease Development ◽  
Cortical Layers ◽  
Critical Function ◽  
Cortical Regions ◽  
Genetic Counseling Programs

AbstractTcf4 has been linked to autism, schizophrenia, and Pitt-Hopkins Syndrome (PTHS) in humans, however, the mechanisms behind its role in disease development is still elusive. In the present study, we provide evidence that Tcf4 has a critical function in the differentiation of cortical regions during development.We show that Tcf4 is present throughout the developing brain at the peak of neurogenesis. Deletion of Tcf4 results in mis-specification of the cortical layers, malformation of the corpus callosum and hypoplasia of the hippocampus. RNA-sequencing on E14.5 cortex material shows that Tcf4 functions as a transcriptional activator and loss of Tcf4 results in downregulation of genes linked to the emergence of other neurodevelopmental disorders. Taken together, we show that neurogenesis and differentiation are severely affected in Tcf4 mutants, phenocopying morphological brain defects detected in PTHS patients. The presented data identifies new leads to understand the mechanism of human brain defects and will assist in genetic counseling programs.

scholarly journals Redundancy Circuits of the Commissural Pathways in Human and Rhesus Macaque Brains

2020 ◽  
Author(s):  
Zulfar Ghulam-Jelani ◽  
Jessica Barrios-Martinez ◽  
Aldo Eguiluz-Melendez ◽  
Ricardo Gomez ◽  
Yury Anania ◽  
...  
Keyword(s):  
Corpus Callosum ◽  
Human Brain ◽  
Rhesus Macaque ◽  
Anterior Commissure ◽  
Brain Disorders ◽  
Commissural Pathways ◽  
Commissural Pathway ◽  
Cortical Regions ◽  
Temporal Redundancy ◽  
First Time

AbstractIt has been hypothesized that the human brain has traded redundancy for efficiency, but the structural existence has not been identified to examine this claim. Here, we report three redundancy circuits of the commissural pathways in primate brains, namely the orbitofrontal, temporal, and occipital redundancy circuits of the anterior commissure and corpus callosum. Each redundancy circuit has two distinctly separated routes connecting a common pair of cortical regions. We mapped their trajectories in human and rhesus macaque brains using individual and population-averaged tractography. The dissection results confirmed the existence of these redundancy circuits connecting the orbitofrontal lobe, amygdala, and visual cortex. The volume analysis showed a significant reduction in the orbitofrontal and occipital redundancy circuits of the human brain, whereas the temporal redundancy circuit had a substantial organizational difference between the human and rhesus macaque. Our overall findings suggest that the human brain is more efficient in the commissural pathway, as shown by the significantly reduced volume of the anterior commissure which serves as the backup connections for the corpus callosum. This reduction of the redundancy circuit may explain why humans are more vulnerable to psychiatric brain disorders stemming from the corpus callosum compared to non-human primates.SignificanceWe report and describe the connection routes of three redundancy circuits of the commissural pathways in human and rhesus macaque brains and compare their volumes. Our tractography and dissection studies confirmed that the human brain has smaller redundancy circuits. This is the first time such redundancy circuits of the commissural pathways have been identified, and their differences quantified in human and rhesus macaque to verify the redundancy-efficiency tradeoff hypothesis. The findings provide new insight into the topological organization of the human brain and may help understand the circuit mechanism of brain disorders involving these pathways.

scholarly journals Shape Profile of Corpus Callosum As a Signature to Phenotype Different Dementia

2020 ◽  
Author(s):  
Sandhya Mangalore ◽  
Shiva Shanker Reddy Mukku ◽  
Sriharish Vankayalapati ◽  
Palanimuthu Thangaraju Sivakumar ◽  
Mathew Varghese
Keyword(s):  
Corpus Callosum ◽  
Frontotemporal Dementia ◽  
Corticobasal Degeneration ◽  
Lewy Body Dementia ◽  
Clinical History ◽  
The Body ◽  
Cortical Atrophy ◽  
Alzheimer Dementia ◽  
Geriatric Clinic ◽  
Cortical Regions

Abstract Background Phenotyping dementia is always a complex task for a clinician. There is a need for more practical biomarkers to aid clinicians. Objective The aim of the study is to investigate the shape profile of corpus callosum (CC) in different phenotypes of dementia. Materials and Methods Our study included patients who underwent neuroimaging in our facility as a part of clinical evaluation for dementia referred from Geriatric Clinic (2017–2018). We have analyzed the shape of CC and interpreted the finding using a seven-segment division. Results The sample included MPRAGE images of Alzheimer’ dementia (AD) (n = 24), posterior cortical atrophy- Alzheimer’ dementia (PCA-AD) (n = 7), behavioral variant of frontotemporal dementia (Bv-FTD) (n = 17), semantic variant frontotemporal dementia (Sv-FTD) (n = 11), progressive nonfluent aphasia (PNFA) (n = 4), Parkinson’s disease dementia (PDD) (n = 5), diffuse Lewy body dementia (n = 7), progressive supranuclear palsy (PSP) (n = 3), and corticobasal degeneration (CBD) (n = 3). We found in posterior dementias such as AD and PCA-AD that there was predominant atrophy of splenium of CC. In Bv-FTD, the genu and anterior half of the body of CC was atrophied, whereas in PNFA, PSP, PDD, and CBD there was atrophy of the body of CC giving a dumbbell like profile. Conclusion Our study findings were in agreement with the anatomical cortical regions involved in different phenotypes of dementia. Our preliminary study highlighted potential usefulness of CC in the clinical setting for phenotyping dementia in addition to clinical history and robust biomarkers.

scholarly journals The Right Hemisphere Is Responsible for the Greatest Differences in Human Brain Response to High-Arousing Emotional versus Neutral Stimuli: A MEG Study

2021 ◽  
Vol 11 (8) ◽  
pp. 960
Author(s):  
Mina Kheirkhah ◽  
Philipp Baumbach ◽  
Lutz Leistritz ◽  
Otto W. Witte ◽  
Martin Walter ◽  
...  
Keyword(s):  
Human Brain ◽  
Right Hemisphere ◽  
Emotional Stimuli ◽  
Brain Response ◽  
Whole Brain ◽  
Brain Responses ◽  
Cortical Regions ◽  
The Right ◽  
Healthy Participants

Studies investigating human brain response to emotional stimuli—particularly high-arousing versus neutral stimuli—have obtained inconsistent results. The present study was the first to combine magnetoencephalography (MEG) with the bootstrapping method to examine the whole brain and identify the cortical regions involved in this differential response. Seventeen healthy participants (11 females, aged 19 to 33 years; mean age, 26.9 years) were presented with high-arousing emotional (pleasant and unpleasant) and neutral pictures, and their brain responses were measured using MEG. When random resampling bootstrapping was performed for each participant, the greatest differences between high-arousing emotional and neutral stimuli during M300 (270–320 ms) were found to occur in the right temporo-parietal region. This finding was observed in response to both pleasant and unpleasant stimuli. The results, which may be more robust than previous studies because of bootstrapping and examination of the whole brain, reinforce the essential role of the right hemisphere in emotion processing.

Developmental trajectory of oligodendrocyte progenitor cells in the human brain revealed by single cell RNA sequencing

Glia ◽  
2020 ◽  
Vol 68 (6) ◽  
pp. 1291-1303 ◽  
Author(s):  
Kelly Perlman ◽  
Charles P. Couturier ◽  
Moein Yaqubi ◽  
Arnaud Tanti ◽  
Qiao‐Ling Cui ◽  
...  
Keyword(s):  
Human Brain ◽  
Single Cell ◽  
Progenitor Cells ◽  
Rna Sequencing ◽  
Developmental Trajectory ◽  
Oligodendrocyte Progenitor Cells ◽  
Oligodendrocyte Progenitor ◽  
Single Cell Rna Sequencing

scholarly journals RNA sequencing of transcriptomes in human brain regions: protein-coding and non-coding RNAs, isoforms and alleles

BMC Genomics ◽  
2015 ◽  
Vol 16 (1) ◽  
Author(s):  
Amy Webb ◽  
Audrey C. Papp ◽  
Amanda Curtis ◽  
Leslie C. Newman ◽  
Maciej Pietrzak ◽  
...  
Keyword(s):  
Human Brain ◽  
Rna Sequencing ◽  
Brain Regions ◽  
Protein Coding ◽  
Non Coding Rnas

scholarly journals Non-local means based Rician noise filtering for diffusion tensor and kurtosis imaging in human brain and spinal cord

2020 ◽  
Author(s):  
Zhongping Zhang ◽  
Dhanashree Vernekar ◽  
Wenshu Qian ◽  
Mina Kim
Keyword(s):  
Spinal Cord ◽  
Corpus Callosum ◽  
Human Brain ◽  
Healthy Subjects ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Chi Square ◽  
Lateral Column ◽  
Diffusion Weighted Images ◽  
The Brain

Abstract Background: To investigate the effect of using an Rician nonlocal means (NLM) filter on quantification of diffusion tensor (DT)- and diffusion kurtosis (DK)-derived metrics in various anatomical regions of the human brain and the spinal cord, when combined with a constrained linear least squares (CLLS) approach.Methods: Prospective brain data from 9 healthy subjects and retrospective spinal cord data from 5 healthy subjects from a 3T MRI scanner were included in the study. Prior to tensor estimation, registered diffusion weighted images were denoised by an optimized blockwise NLM filter with CLLS. Mean kurtosis (MK), radial kurtosis (RK), axial kurtosis (AK), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD) and fractional anisotropy (FA), were determined in anatomical structures of the brain and the spinal cord. DTI and DKI metrics, signal-to-noise ratio (SNR) and Chi-square values were quantified in distinct anatomical regions for all subjects, with and without Rician denoising. Results: The averaged SNR significantly increased with Rician denoising by a factor of 2 while the averaged Chi-square values significantly decreased up to 61 % in the brain and up to 43% in the spinal cord after Rician NLM filtering. In the brain, the mean MK varied from 0.70 (putamen) to 1.27 (internal capsule) while AK and RK varied from 0.58 (corpus callosum) to 0.92 (cingulum) and from 0.70 (putamen) to 1.98 (corpus callosum), respectively. In the spinal cord, FA varied from 0.78 in lateral column to 0.81 in dorsal column while MD varied from 0.91 × 10−3 mm2/s (lateral) to 0.93 × 10−3 mm2/s (dorsal). RD varied from 0.34 × 10−3 mm2/s (dorsal) to 0.38 × 10−3 mm2/s (lateral) and AD varied from 1.96 × 10−3 mm2/s (lateral) to 2.11 × 10−3 mm2/s (dorsal).Conclusions: Our results show Rician denoising NLM filter incorporated with CLLS significantly increases SNR and reduces estimation errors of DT- and KT-derived metrics, providing the reliable metrics estimation with adequate SNR levels.

scholarly journals Human brain harbors single nucleotide somatic variations in functionally relevant genes possibly mediated by oxidative stress

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2520 ◽  
Author(s):  
Anchal Sharma ◽  
Asgar Hussain Ansari ◽  
Renu Kumari ◽  
Rajesh Pandey ◽  
Rakhshinda Rehman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Corpus Callosum ◽  
Human Brain ◽  
Frontal Cortex ◽  
Oxidative Stress Marker ◽  
Somatic Variation ◽  
Single Nucleotide ◽  
Normal Human Brain ◽  
Normal Human ◽  
The Brain

Somatic variation in DNA can cause cells to deviate from the preordained genomic path in both disease and healthy conditions. Here, using exome sequencing of paired tissue samples, we show that the normal human brain harbors somatic single base variations measuring up to 0.48% of the total variations. Interestingly, about 64% of these somatic variations in the brain are expected to lead to non-synonymous changes, and as much as 87% of these represent G:C>T:A transversion events. Further, the transversion events in the brain were mostly found in the frontal cortex, whereas the corpus callosum from the same individuals harbors the reference genotype. We found a significantly higher amount of 8-OHdG (oxidative stress marker) in the frontal cortex compared to the corpus callosum of the same subjects (p<0.01), correlating with the higher G:C>T:A transversions in the cortex. We found significant enrichment for axon guidance and related pathways for genes harbouring somatic variations. This could represent either a directed selection of genetic variations in these pathways or increased susceptibility of some loci towards oxidative stress. This study highlights that oxidative stress possibly influence single nucleotide somatic variations in normal human brain.

Localization of migraine susceptibility genes in human brain by single-cell RNA sequencing

Cephalalgia ◽  
2018 ◽  
Vol 38 (13) ◽  
pp. 1976-1983 ◽  
Author(s):  
William Renthal
Keyword(s):  
Human Brain ◽  
Single Cell ◽  
Rna Sequencing ◽  
Expression Profiles ◽  
Cell Types ◽  
Susceptibility Genes ◽  
Brain Cell ◽  
Cell Type ◽  
Single Cell Rna Sequencing ◽  
Brain Cell Types

Background Migraine is a debilitating disorder characterized by severe headaches and associated neurological symptoms. A key challenge to understanding migraine has been the cellular complexity of the human brain and the multiple cell types implicated in its pathophysiology. The present study leverages recent advances in single-cell transcriptomics to localize the specific human brain cell types in which putative migraine susceptibility genes are expressed. Methods The cell-type specific expression of both familial and common migraine-associated genes was determined bioinformatically using data from 2,039 individual human brain cells across two published single-cell RNA sequencing datasets. Enrichment of migraine-associated genes was determined for each brain cell type. Results Analysis of single-brain cell RNA sequencing data from five major subtypes of cells in the human cortex (neurons, oligodendrocytes, astrocytes, microglia, and endothelial cells) indicates that over 40% of known migraine-associated genes are enriched in the expression profiles of a specific brain cell type. Further analysis of neuronal migraine-associated genes demonstrated that approximately 70% were significantly enriched in inhibitory neurons and 30% in excitatory neurons. Conclusions This study takes the next step in understanding the human brain cell types in which putative migraine susceptibility genes are expressed. Both familial and common migraine may arise from dysfunction of discrete cell types within the neurovascular unit, and localization of the affected cell type(s) in an individual patient may provide insight into to their susceptibility to migraine.

Analysis of 3D Corpus Callosum Images in the Brains of Autistic Individuals

2016 ◽  
pp. 159-184
Author(s):  
Ahmed Elnakib ◽  
Manuel F. Casanova ◽  
Ahmed Soliman ◽  
Georgy Gimel'farb ◽  
Ayman El-Baz
Keyword(s):  
Autism Spectrum Disorder ◽  
Corpus Callosum ◽  
Human Brain ◽  
Shape Analysis ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Cerebral Hemispheres ◽  
Higher Cognitive Functions ◽  
The Right ◽  
Abnormal Anatomy

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that is characterized by abnormalities in behavior and higher cognitive functions. The corpus callosum (CC) is the largest fiber bundle that connects the left and the right cerebral hemispheres of the human brain. Several studies have revealed an abnormal anatomy of the CC in the brains of autistic individuals that associates this neurodevelopmental condition with impaired communication between the hemispheres. In this chapter, we develop a framework to analyze the CC of autistic individuals in order to provide a diagnostic tool for autism. The key advantage of this approach is the development of a cylindrical mapping that offers simplified coordinates for comparing the brains of autistic individuals and neurotypicals. Experimental results showed significant differences (at the 95% confidence level) between 17 normal and 17 autistic subjects in four anatomical divisions, i.e. splenium, rostrum, genu, and body of their CCs. Moreover, the initial centerline-based shape analysis of the CC documented a promising supplement to the current techniques for diagnosing autism.

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