Abstract:
:Phencyclidine (PCP), a noncompetitive N-methyl-D-aspartate receptor antagonist, induces psychotomimetic effects in humans and animals. Administration of PCP to rodents is used as a preclinical model for schizophrenia; however, the molecular mechanisms underlying the symptoms remain largely unknown. Acute PCP treatment rapidly induces behavioral and cognitive deficits; therefore, post-translational regulation of protein activity is expected to play a role at early time points. We performed mass-spectrometry-driven quantitative analysis of rat frontal cortex 15, 30, or 240 min after the administration of PCP (10 mg/kg). We identified and quantified 23,548 peptides, including 4749 phosphopeptides, corresponding to 2604 proteins. A total of 352 proteins exhibited altered phosphorylation levels, indicating that protein phosphorylation is involved in the acute response to PCP. Computational assessment of the regulated proteins biological function revealed that PCP perturbs key processes in the frontal cortex including calcium homeostasis, organization of cytoskeleton, endo/exocytosis, and energy metabolism. This study on acute PCP treatment provides the largest proteomics and phosphoproteomics data sets to date of a preclinical model of schizophrenia. Our findings contribute to the understanding of alterations in glutamatergic neurotransmission in schizophrenia and provide a foundation for discovery of novel targets for pharmacological intervention.
journal_name
J Proteome Resjournal_title
Journal of proteome researchauthors
Palmowski P,Rogowska-Wrzesinska A,Williamson J,Beck HC,Mikkelsen JD,Hansen HH,Jensen ONdoi
10.1021/pr4010794subject
Has Abstractpub_date
2014-03-07 00:00:00pages
1578-92issue
3eissn
1535-3893issn
1535-3907journal_volume
13pub_type
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journal_title:Journal of proteome research
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journal_title:Journal of proteome research
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journal_title:Journal of proteome research
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doi:10.1021/pr049819s
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journal_title:Journal of proteome research
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journal_title:Journal of proteome research
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journal_title:Journal of proteome research
pub_type: 杂志文章
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journal_title:Journal of proteome research
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