Validated UPLC-MS/MS method for determination of moclobemide in human brain cell supernatant and its application to bidirectional transport study

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.

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Determination of Chol-1 Antigen in Human Brain and Neuroblastoma Tumor

Gangliosides and Modulation of Neuronal Functions ◽

10.1007/978-3-642-71932-5_41 ◽

1987 ◽

pp. 455-457

Author(s):

Marie-Odile Jauberteau ◽

P. Richardson ◽

M. L. Harpin ◽

N. Baumann

Keyword(s):

Human Brain ◽

Neuroblastoma Tumor

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Topical Review: Cortical Malformation and Pediatric Epilepsy: A Molecular Genetic Approach

Journal of Child Neurology ◽

10.1177/08830738040190030501 ◽

2004 ◽

Vol 19 (3) ◽

pp. 300-303

Author(s):

Ganeshwaran H. Mochida

Keyword(s):

Human Brain ◽

Cell Fate ◽

Molecular Genetic ◽

Pediatric Epilepsy ◽

Causative Gene ◽

Cortical Malformation ◽

Neuronal Progenitor ◽

Cortical Patterning ◽

Low Incidence

Genetic malformations of the cerebral cortex are important causes of neurologic morbidity in children because they are often associated with developmental delay, motor disturbances (cerebral palsy), and epilepsy. Primary autosomal recessive microcephaly is a cortical malformation with a low incidence of epilepsy. One of its causative genes, ASPM, might play an important role in regulating proliferation of neuronal progenitor cells. Mutations in ASPM do not seem to affect later stages of cortical development, such as neuronal migration, and this might be responsible for the low epileptogenicity of this malformation. ASPM might also have played an important role in the evolutionary expansion of the human brain. Bilateral frontoparietal polymicrogyria, on the other hand, is a highly epileptogenic malformation. Its causative gene, GPR56 , is also expressed in the neurogenic regions of the cortex, but its primary function might be in the determination of cell fate and/or cortical patterning. Further studies of these genes will likely lead to a better understanding of human brain development and epilepsy. ( J Child Neurol 2005;20:300—303).

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Novel and sensitive reversed-phase high-pressure liquid chromatography method with electrochemical detection for the simultaneous and fast determination of eight biogenic amines and metabolites in human brain tissue

Journal of Chromatography A ◽

10.1016/j.chroma.2014.05.004 ◽

2014 ◽

Vol 1353 ◽

pp. 28-39 ◽

Cited By ~ 24

Author(s):

Debby Van Dam ◽

Yannick Vermeiren ◽

Tony Aerts ◽

Peter Paul De Deyn

Keyword(s):

High Pressure ◽

Liquid Chromatography ◽

Human Brain ◽

Electrochemical Detection ◽

Reversed Phase ◽

Human Brain Tissue ◽

Chromatography Method ◽

Fast Determination ◽

Liquid Chromatography Method

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Quantification of Neuroreceptors in the Living Human Brain. II. Inhibition Studies of Receptor Density and Affinity

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1986.28 ◽

1986 ◽

Vol 6 (2) ◽

pp. 147-153 ◽

Cited By ~ 108

Author(s):

Dean F. Wong ◽

Albert Gjedde ◽

Henry N. Wagner ◽

Robert F. Dannals ◽

Kenneth H. Douglass ◽

...

Keyword(s):

Human Brain ◽

Blocking Agent ◽

Receptor Density ◽

Positron Emission ◽

Tracer Accumulation ◽

Inhibition Studies ◽

Human Autopsy Material ◽

Human Autopsy

A method for estimating receptor density ( Bmax) in the living human brain by positron emission tomography was exemplified by a ligand, 3- N-[11C]methylspiperone ([11C]NMSP), that binds to D2 dopamine receptors with high affinity. The ligand binds essentially irreversibly (i.e., with very little dissociation) to the receptors during the 2-h scanning period. Transfer constants were estimated at steady state. In a previous article, we presented a method for the determination of k3, the rate of binding of the labeled ligand. In the present work, we varied k3 by reducing the number of available receptors with a previously administered receptor blocking agent, haloperidol. We calculated a receptor density of 9.2 pmol g−1 in the caudate nucleus of four normal volunteers, and an inhibitory constant of haloperidol of 1.4 n M by comparing tracer accumulation in the absence and the presence of the blocking agent. The values agreed with measurements of NMSP receptor density and haloperidol inhibitory potency in vitro in brain homogenates from human autopsy material.

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