Dataset Information

Human Globus Pallidus (GP) from Non-Hispanic Whites and African Americans with and without Alzheimer's disease LC-MS3

ABSTRACT: This study examined global proteomic changes in postmortem globus pallidus (GP) tissue from Non-Hispanic Whites and African American individuals who were cognitively normal or had Alzheimer's disease using LC-MS3 on an Orbitrap Fusion Lumos. Proteins were quantified in the LC-MS3 experiments using Tandem Mass Tags (TMT)10plex.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

DISEASE(S): Alzheimer's Disease

SUBMITTER: Kaitlyn Stepler

LAB HEAD: Renã A.S. Robinson

PROVIDER: PXD014371 | Pride | 2020-10-19

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	GP_Batch1_Frac10_TR1_Redo.msf	Msf
	GP_Batch1_Frac10_TR1_Redo.raw	Raw
	GP_Batch1_Frac10_TR2_Redo.msf	Msf
	GP_Batch1_Frac10_TR2_Redo.raw	Raw
	GP_Batch1_Frac11_TR1.msf	Msf

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Publications

Inclusion of African American/Black adults in a pilot brain proteomics study of Alzheimer's disease.

Stepler Kaitlyn E KE Mahoney Emily R ER Kofler Julia J Hohman Timothy J TJ Lopez Oscar L OL Robinson Renã A S RAS

Neurobiology of disease 20201010

Alzheimer's disease (AD) disproportionately affects certain racial and ethnic subgroups, such as African American/Black and Hispanic adults. Genetic, comorbid, and socioeconomic risk factors contribute to this disparity; however, the molecular contributions have been largely unexplored. Herein, we conducted a pilot proteomics study of postmortem brains from African American/Black and non-Hispanic White adults neuropathologically diagnosed with AD compared to closely-matched cognitively normal in ...[more]

PMID: 33049317

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Project description:Molecular basis of transition to addiction in vulnerable individuals is largely unknown. We hypothesized that human susceptibility genes can be identified on the basis of conserved molecular mechanisms in rodent brains. We used a short-term cocaine-dependent conditioned place preference (CPP) to identify genetic hallmarks of early steps of reward memory in basal ganglia including accumbens nucleus (NAc), globus pallidus (GP) and subthalamic nucleus (STN). Using genome-wide microarray analysis and CPP as a quantitative trait, we found that synaptic plasticity-related genes are deregulated in these three structures. A significant enrichment in bona fide transcripts involved in dendritic spine local translation was evidenced. mGluR5 is transcriptionally deregulated in Acc and GP of cocaine-treated animals. Grin3a that encodes a NMDA receptor subunit involved in Ca++ permeability is deregulated in NAc. Furthermore, Orexin/Hcrt transcript level is decreased in STN, a region known to be involved in discriminating addictive drugs and natural rewards. We also found that mGluR5 and Grin3a expression deregulation is sufficient to induce changes in synaptic plasticity-related genes. Altogether, these results suggest that a combined deregulation of mGluR5 and Grin3A pathway in NAc, mGluR5 in GP and orexin system in STN may generate an incentive memory contrasted between addictive drugs and natural rewards. Such pathways may include clusters of genes that are potential susceptibility genes for transition to addiction. Agilent Whole Mouse Genome oligomicroarrays (GEO accession no. GPL4134, Agilent Technologies, Palo Alto, CA) were used. They contain 60-mer DNA probes synthesized in situ in a 44k format. Four independent (globus pallidus from mouse treated with cocaine and having a low score of conditioned place preference compared to globus pallidus from mouse treated with saline solution) hybridizations were carried out for each group of biological conditions using exchanged dye-labeled RNA targets (i.e., Cy3 and Cy5 dyeswapping experiments).

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