Time-dependent changes in gene expression profiles of midbrain dopamine neurons following haloperidol administration

The ability to microdissect individual cells from the nervous system has enormous potential, as it can allow for the study of gene expression in phenotypically identified cells. However, if the resultant gene expression profiles are to be accurately ascribed, it is necessary to determine the extent of contamination by nontarget cells in the microdissected sample. Here, we show that midbrain dopamine neurons can be laser-microdissected to a high degree of enrichment and purity. The average enrichment for tyrosine hydroxylase (TH) gene expression in the microdissected sample relative to midbrain sections was approximately 200-fold. For the dopamine transporter (DAT) and the vesicular monoamine transporter type 2 (Vmat2), average enrichments were approximately 100- and 60-fold, respectively. Glutamic acid decarboxylase (Gad65) expression, a marker for GABAergic neurons, was several hundredfold lower than dopamine neuron-specific genes. Glial cell and glutamatergic neuron gene expression were not detected in microdissected samples. Additionally, SN and VTA dopamine neurons had significantly different expression levels of dopamine neuron-specific genes, which likely reflects functional differences between the two cell groups. This study demonstrates that it is possible to laser-microdissect dopamine neurons to a high degree of cell purity. Therefore gene expression profiles can be precisely attributed to the targeted microdissected cells.

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Time Dependent Gene Expression Changes in the Liver of Mice Treated with Benzene

Biomarker Insights ◽

10.4137/bmi.s590 ◽

2008 ◽

Vol 3 ◽

pp. BMI.S590 ◽

Cited By ~ 3

Author(s):

Han-Jin Park ◽

Jung Hwa Oh ◽

Seokjoo Yoon ◽

S.V.S. Rana

Keyword(s):

Gene Expression ◽

Expression Profiles ◽

Gene Expression Profiles ◽

General Purpose ◽

Time Dependent ◽

Expression Data ◽

Benzene Exposure ◽

Microarray Analyses ◽

First Time ◽

Affymetrix Gene Chip

Benzene is used as a general purpose solvent. Benzene metabolism starts from phenol and ends with p-benzoquinone and o-benzoquinone. Liver injury inducted by benzene still remains a toxicologic problem. Tumor related genes and immune responsive genes have been studied in patients suffering from benzene exposure. However, gene expression profiles and pathways related to its hepatotoxicity are not known. This study reports the results obtained in the liver of BALB/C mice (SLC, Inc., Japan) administered 0.05 ml/100 g body weight of 2% benzene for six days. Serum, ALT, AST and ALP were determined using automated analyzer (Fuji., Japan). Histopathological observations were made to support gene expression data. c-DNA microarray analyses were performed using Affymetrix Gene-chip system. After six days of benzene exposure, twenty five genes were down regulated whereas nineteen genes were up-regulated. These gene expression changes were found to be related to pathways of biotransformation, detoxification, apoptosis, oxidative stress and cell cycle. It has been shown for the first time that genes corresponding to circadian rhythms are affected by benzene. Results suggest that gene expression profile might serve as potential biomarkers of hepatotoxicity during benzene exposure.

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Gene expression profiling of midbrain dopamine neurons upon gestational nicotine exposure

Medical & Biological Engineering & Computing ◽

10.1007/s11517-016-1531-8 ◽

2016 ◽

Vol 55 (3) ◽

pp. 467-482 ◽

Cited By ~ 6

Author(s):

Pınar Kanlikilicer ◽

Die Zhang ◽

Andrei Dragomir ◽

Yasemin M. Akay ◽

Metin Akay

Keyword(s):

Gene Expression ◽

Gene Expression Profiling ◽

Expression Profiling ◽

Dopamine Neurons ◽

Nicotine Exposure ◽

Midbrain Dopamine ◽

Midbrain Dopamine Neurons ◽

Gestational Nicotine

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Photo-caged agonists of the nuclear receptors RARγ and TRβ provide unique time-dependent gene expression profiles for light-activated gene patterning

Bioorganic & Medicinal Chemistry ◽

10.1016/j.bmc.2004.08.022 ◽

2004 ◽

Vol 12 (22) ◽

pp. 5949-5959 ◽

Cited By ~ 15

Author(s):

Kristian H. Link ◽

Federico G. Cruz ◽

Hai-Fen Ye ◽

Kathryn E. O’Reilly ◽

Sarah Dowdell ◽

...

Keyword(s):

Gene Expression ◽

Nuclear Receptors ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Time Dependent ◽

Gene Patterning

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Neuropeptide gene expression in brain is differentially regulated by midbrain dopamine neurons

Experimental Brain Research ◽

10.1007/bf00227990 ◽

1990 ◽

Vol 80 (3) ◽

Cited By ~ 60

Author(s):

N. Lindefors ◽

S. Bren� ◽

M. Herrera-Marschitz ◽

H. Persson

Keyword(s):

Gene Expression ◽

Dopamine Neurons ◽

Midbrain Dopamine ◽

Midbrain Dopamine Neurons

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Classification of Midbrain Dopamine Neurons Using Single-Cell Gene Expression Profiling Approaches

Trends in Neurosciences ◽

10.1016/j.tins.2020.01.004 ◽

2020 ◽

Vol 43 (3) ◽

pp. 155-169 ◽

Cited By ~ 15

Author(s):

Jean-Francois Poulin ◽

Zachary Gaertner ◽

Oscar Andrés Moreno-Ramos ◽

Rajeshwar Awatramani

Keyword(s):

Gene Expression ◽

Single Cell ◽

Gene Expression Profiling ◽

Expression Profiling ◽

Dopamine Neurons ◽

Cell Gene Expression ◽

Midbrain Dopamine ◽

Cell Gene ◽

Midbrain Dopamine Neurons

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Abstract P744: Gene Transcript Clusters Distinguish Time-Dependent Expression Patterns in Monocytes, Neutrophils and Whole Blood After Ischemic Stroke Injury

Stroke ◽

10.1161/str.52.suppl_1.p744 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Paulina Carmona-Mora ◽

Glen C Jickling ◽

Xinhua Zhan ◽

Marisa Hakoupian ◽

Heather Hull ◽

...

Keyword(s):

Gene Expression ◽

Ischemic Stroke ◽

Whole Blood ◽

Temporal Dynamics ◽

Expression Profiles ◽

Expression Patterns ◽

Gene Expression Profiles ◽

Time Dependent ◽

Gene Transcript ◽

Time Points

Introduction: After ischemic stroke (IS), peripheral leukocytes infiltrate the damaged region and modulate the response to injury. We previously showed that peripheral blood cells display different gene expression profiles after IS and these transcriptional programs reflect the changes in immune processes in response to IS. Dissecting the temporal dynamics of gene expression after IS improves our understanding of the changes of molecular and cellular pathways involved in acute brain injury. Methods: We analyzed the transcriptomic profiles of 33 IS patients in isolated monocytes, neutrophils and whole blood. RNA-sequencing was performed on all the stroke samples as well as 12 controls with vascular risk factors (diabetes and/or hypertension and/or hypercholesterolemia). To identify differentially expressed genes, subjects were split into time points (TPs) from stroke onset (TP1= 0-24 h; TP2= 24-48 h; and TP3= > 48 h), and controls were assigned TP0. A linear regression model including time and the interaction of diagnosis x TP with cutoff of p<0.02 and fold-change>|1.2| was used. Time dependent changes were analyzed using artificial neural networks to identify clusters of genes that behave in a similar way across TPs. Results: Unique patterns of temporal expression were distinguished for the three sample types. These include genes not expressed in TP0 that peak only within the first 24 h, others that peak or decrease in TP2 and TP3, and more complex patterns. Genes that peak at TP1 in monocytes and neutrophils are related to cell adhesion and leukocyte differentiation/migration, respectively. Early peaks in whole blood occur in genes related to transcriptional regulation. In monocytes, interleukin pathways are enriched across all TPs, whereas there is a trend of suppression after 24 h in neutrophils. The inflammasome pathway is enriched in the earlier TPs in neutrophils, while not enriched in monocytes until over 48 hours. Conclusion: Our analyses on gene expression dynamics and cluster patterns allow identification of key genes and pathways at different time points following ischemic injury that are valuable as IS biomarkers and may be possible treatment targets.

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