PXD019485

PXD019485 is an original dataset announced via ProteomeXchange.

Title	Granulocyte-Colony Stimulating Factor reduces cocaine-seeking and downregulates glutamatergic synaptic proteins in medial prefrontal cortex
Description	Abstract Background Psychostimulant use disorder is a major public health issue, and despite the scope of the problem there are currently no FDA approved treatments. There would be tremendous utility in development of a treatment that could help patients both achieve and maintain abstinence. Previous work from our group has identified granulocyte-colony stimulating factor (G-CSF) as a neuroactive cytokine that alters behavioral response to cocaine, increases synaptic dopamine release, and enhances cognitive flexibility. Here, we investigate the role of G-CSF in affecting extinction and reinstatement of cocaine-seeking and perform detailed characterization of its proteomic effects in multiple limbic substructures. Methods Sprague-Dawley rats were injected with PBS or G-CSF during (1) extinction or (2) abstinence from cocaine self-administration, and drug seeking behavior was measured. Quantitative assessment of changes in the proteomic landscape in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) were performed via data-independent acquisition (DIA) mass spectrometry analysis. Results Administration of G-CSF during extinction accelerated the rate of extinction, and administration during abstinence attenuated cue-induced cocaine-seeking. Analysis of global protein expression demonstrated that G-CSF regulated proteins primarily in mPFC that are critical to glutamate signaling and synapse maintenance. Conclusion Taken together, these findings support G-CSF as a viable translational research target with the potential to reduce drug craving or seeking behaviors. Importantly, recombinant G-CSF exists as an FDA-approved medication which may facilitate rapid clinical translation. Additionally, using cutting-edge multi-region discovery proteomics analyses, these studies identify a novel mechanism underlying G-CSF effects on behavioral plasticity.
HostingRepository	PRIDE
AnnounceDate	2021-01-29
AnnouncementXML	Submission_2021-01-29_04:47:13.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tanner Euston
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-06-01 03:10:27	ID requested
1	2021-01-28 11:19:05	announced
2	2021-01-29 04:44:46	announced	2021-01-29: Updated project metadata.
⏵ 3	2021-01-29 04:47:14	announced	2021-01-29: Updated project metadata. 2021-01-29: Updated publication reference for PubMed record(s): 33361463. 2021-01-29: Updated publication reference for DOI(s): 10.1523/JNEUROSCI.1452-20.2020.

10.1523/JNEUROSCI.1452-20.2020;

Hofford RS, Euston TJ, Wilson RS, Meckel KR, Peck EG, Godino A, Landry JA, Calipari ES, Lam TT, Kiraly DD, Granulocyte-Colony Stimulating Factor Reduces Cocaine-Seeking and Downregulates Glutamatergic Synaptic Proteins in Medial Prefrontal Cortex. J Neurosci, 41(7):1553-1565(2021) [pubmed]

submitter keyword: cocaine, reinstatement, glutamate, granulocyte-colony stimulating factor, neuroimmune

Drew D. Kiraly
contact affiliation	Kiraly Lab Dept of Psychiatry Friedman Brain Institue Icahn School of Medicine at Mount Sinai
contact email	drew.kiraly@mssm.edu
lab head
Tanner Euston
contact affiliation	Mount Sinai Hospital
contact email	tanner.euston@kiralylab.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD019485
     1. Label: PRIDE project
     2. Name: Granulocyte-Colony Stimulating Factor reduces cocaine-seeking and downregulates glutamatergic synaptic proteins in medial prefrontal cortex