Decision letter for "An open access mouse brain flatmap and upgraded rat and human brain flatmaps based on current reference atlases"


2020 ◽  
Author(s):  
Joel D. Hahn ◽  
Larry W. Swanson ◽  
Ian Bowman ◽  
Nicholas N. Foster ◽  
Brian Zingg ◽  
...  


2020 ◽  
Vol 529 (3) ◽  
pp. 576-594 ◽  
Author(s):  
Joel D. Hahn ◽  
Larry W. Swanson ◽  
Ian Bowman ◽  
Nicholas N. Foster ◽  
Brian Zingg ◽  
...  


2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
C. A. Acevedo-Triana ◽  
L. A. León ◽  
F. P. Cardenas

Brain atlases are tools based on comprehensive studies used to locate biological characteristics (structures, connections, proteins, and gene expression) in different regions of the brain. These atlases have been disseminated to the point where tools have been created to store, manage, and share the information they contain. This study used the data published by the Allen Mouse Brain Atlas (2004) for mice (C57BL/6J) and Allen Human Brain Atlas (2010) for humans (6 donors) to compare the expression of serotonin-related genes. Genes of interest were searched for manually in each case (in situ hybridization for mice and microarrays for humans), normalized expression data (z-scores) were extracted, and the results were graphed. Despite the differences in methodology, quantification, and subjects used in the process, a high degree of similarity was found between expression data. Here we compare expression in a way that allows the use of translational research methods to infer and validate knowledge. This type of study allows part of the relationship between structures and functions to be identified, by examining expression patterns and comparing levels of expression in different states, anatomical correlations, and phenotypes between different species. The study concludes by discussing the importance of knowing, managing, and disseminating comprehensive, open-access studies in neuroscience.



2021 ◽  
Author(s):  
Jennifer S Goldman ◽  
Lionel Kusch ◽  
Bahar Hazal Yalcinkaya ◽  
Damien Depannemaecker ◽  
Trang-Anh Estelle Nghiem ◽  
...  

Hallmarks of neural dynamics during healthy human brain states span spatial scales from neuromodulators acting on microscopic ion channels to macroscopic changes in communication between brain regions. Developing a scale-integrated understanding of neural dynamics has therefore remained challenging. Here, we perform the integration across scales using mean-field modeling of Adaptive Exponential (AdEx) neurons, explicitly incorporating intrinsic properties of excitatory and inhibitory neurons. We report that when AdEx mean-field neural populations are connected via structural tracts defined by the human connectome, macroscopic dynamics resembling human brain activity emerge. Importantly, the model can qualitatively and quantitatively account for properties of empirical spontaneous and stimulus-evoked dynamics in the space, time, phase, and frequency domains. Remarkably, the model also reproduces brain-wide enhanced responsiveness and capacity to encode information particularly during wake-like states, as quantified using the perturbational complexity index. The model was run using The Virtual Brain (TVB) simulator, and is open-access in EBRAINS. This approach not only provides a scale-integrated understanding of brain states and their underlying mechanisms, but also open access tools to investigate brain responsiveness, toward producing a more unified, formal understanding of experimental data from conscious and unconscious states, as well as their associated pathologies.



2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi86-vi86
Author(s):  
Xun Bao ◽  
Jianmei Wu ◽  
Youming Xie ◽  
Seongho Kim ◽  
Sharon Michelhaugh ◽  
...  

Abstract BACKGROUND Mechanistic understanding and quantitative prediction of drug penetration across the human blood-brain barrier (BBB) is critical to rational drug development and treatment for brain cancer especially glioblastoma. However, prediction of drug brain/tumor penetration has been significantly hindered mainly due to the lack of quantitation data on transporter protein expression levels at the human BBB. This study was to determine protein expression levels of major transporters and markers at the BBB of human brain and glioblastoma. METHOD The absolute protein expression levels of major transporters and markers were determined in isolated microvessels of human brain (N=30), glioblastoma (N=47), rat (N=10) and mouse brain (N=10), using liquid chromatography with tandem mass spectrometry (LC-MS/MS) based targeted proteomics. RESULTS In isolated microvessels of 30 human brain specimens, the median protein abundances for ABCB1, ABCG2, GLUT1, GLUT3, LAT1, MCT1, Na/K ATPase, and Claudin-5 were 3.38, 6.21, 54.51, 7.17, 3.42, 5.71, 32.14, and 1.15 fmol/µg protein, respectively. In glioblastoma microvessels, ABCB1, ABCG2, MCT1, GLUT1, Na/K ATPase, and Claudin-5 protein levels were significantly reduced, while LAT1 was increased and GLU1 remained the same. ABCC4, OATP1A2, OATP2B1, and OAT3 were undetectable in isolated microvessels of both human brain and glioblastoma. There was species difference in transporter protein expression levels in isolated microvessels of human, rat and mouse brain. Specifically, rodent BBB expressed significantly higher ABCB1 but similar ABCG2, as compared to human BBB. CONCLUSION The physical and biochemical barriers of the BBB in glioblastomas are largely disrupted, as indicated by the loss or significant reduction in protein expression of the tight junction marker (claudin-5), brain endothelial cell marker (GLUT1), and major efflux transporters (ABCB1 and ABCG2) as compared to normal human BBB. Differential BBB transporter protein expression levels provides mechanistic and quantitative basis for the prediction of heterogeneous drug penetration into human normal brain and glioblastoma.



Author(s):  
Gang Xu ◽  
Philip V. Bayly ◽  
Larry A. Taber

Proper folding of the cerebral cortex is critical to normal human brain function. The mechanisms of cortical folding, however, remain incompletely understood, although they have intrigued neuroscientists for more than a century. Clearly a biomechanical problem, cortical folding has been speculated to result from stresses induced by differential or constrained growth [1]. More recently, investigators have postulated that tension in neural axons of cerebral white matter causes specific folding patterns [2]. However, it is uncertain if sustained tension exists in axons in both the developing and mature brain.



1990 ◽  
Vol 271 (2) ◽  
pp. 559-562 ◽  
Author(s):  
A V Bakker ◽  
S Jung ◽  
R W Spencer ◽  
F J Vinick ◽  
W S Faraci

Prolyl endopeptidase is a serine proteinase that specifically cleaves peptides on the carboxy side of proline residues. Wilk & Orlowski [(1983) J. Neurochem. 41, 69-75] have shown that benzyloxycarbonyl-prolyl-prolinal (Z-prolyl-prolinal) is a potent inhibitor of prolyl endopeptidase. We show that Z-prolyl-prolinal is a slow-binding inhibitor of mouse brain prolyl endopeptidase with Ki 0.35 +/- 0.05 nM. Kinetic analysis indicates that the mechanism is a simple, but slow, reversible equilibrium between free and bound enzyme (E + I in equilibrium EI) with rate constants for association (kon) and dissociation (koff) of 1.6 X 10(5) M-1.s-1 and approx. 4 X 10(-5) s-1 respectively. Slow-binding inhibition is dependent on the presence of the aldehyde group since the alcohol (Z-prolyl-prolinol) is a rapid and 50,000-fold poorer inhibitor (Ki 19 microM). Prolyl endopeptidase from human brain is also inhibited by Z-prolyl-prolinal with kinetics similar to those of the mouse brain enzyme.



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