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A quantitative peptidomic analysis of peptides related to the endogenous opioid and tachykinin systems in nucleus accumbens of rats following naloxone-precipitated morphine withdrawal
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Biological Research on Drug Dependence.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Medicinsk masspektrometri)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Medicinsk masspektrometri)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
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2009 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 8, no 2, 1091-1098 p.Article in journal (Refereed) Published
Abstract [en]

We have applied a recently developed label-free mass spectrometry based peptidomic approach to identify and quantify a variety of endogenous peptides from rat nucleus accumbens following withdrawal in naloxone-precipitated, morphine-dependent rats of two separate strains. We focused on maturated, partially processed and truncated peptides derived from the peptide precursors proenkephalin, prodynorphin and preprotachykinin. The expression of several identified peptides was dependent on strain and was affected during morphine withdrawal.

Place, publisher, year, edition, pages
2009. Vol. 8, no 2, 1091-1098 p.
Keyword [en]
Peptidome, rat brain, Morphine, Opioid peptides, Tachykinins, Withdrawal
National Category
Neurosciences
Research subject
Neuroscience
Identifiers
URN: urn:nbn:se:uu:diva-108890DOI: 10.1021/pr800669gISI: 000263193300070PubMedID: 19159213OAI: oai:DiVA.org:uu-108890DiVA: diva2:241303
Available from: 2009-10-02 Created: 2009-10-02 Last updated: 2017-12-13Bibliographically approved
In thesis
1. The Impact of Drugs of Abuse on the Neuroproteome: Application of Immunoblotting and LC-MS-based Proteomics
Open this publication in new window or tab >>The Impact of Drugs of Abuse on the Neuroproteome: Application of Immunoblotting and LC-MS-based Proteomics
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Qualitative and quantitative analysis of proteins can be based either on immunological or on mass spectrometry-utilizing methods. In this thesis, different approaches of protein analysis were applied to elucidate the impact of drugs of abuse on the rat brain.

Androgens have been reported to affect mood, anxiety and memory function. The hippocampus plays an important role in memory formation, and studies have reported androgen-induced alteration in hippocampal dendritic spine density. The process of memory and learning requires synaptic plasticity, which depends on key components of signaling pathways, e.g. the ERK and the NMDA receptor. Often, misuse of anabolic androgenic steroids (AAS) leads to administration of supratherapeutical doses with partly unknown impact on the brain.

Rapid and subchronic effects of high AAS doses on proteins of a synapse-enriched rat hippocampal preparation (synaptoneurosomes) were investigated using the immunoblot technique and mass spectrometry. A single high dose of the AAS nandrolone decanoate was found to increase the in vivo phosphorylation of both NMDA receptor subunits and ERKs 24 h after administration. Subchronic treatment with multiple doses showed no effect. A subsequent study focused on rapid effects of the free nandrolone. The phosphorylation of the NMDA receptor subunit GluN2B and ERK1 was found diminished after 2 h and restored after 6 h. This suggests a biphasic impact of nandrolone on signaling components. Moreover, this study aimed to elucidate whether the effects were mediated via the androgen receptor (AR). The AR antagonist flutamide abolished AAS-induced effects. Determination of the CaMKIIα and ephrinB2 proteins, being a potential link of the analogous phosphorylation of NMDA receptor and ERK, could be excluded. Proteins involved in synaptogenesis were not found to be altered. A mass spectrometry-based study was conducted to screen for phosphoproteins and their potential alteration 2 h after a single dose of nandrolone. This analysis identified several proteins with known and not yet described phosphorylation sites. A differential analysis of the identified phosphoproteins was performed.

In a fourth study, quantitative MS-based peptidomics were applied to investigate endogenous neuropeptides in the mesolimbic system during morphine withdrawal. Moreover, strain-dependence was investigated. In accordance to earlier reports, comparable regulation was observed of proenkephalin-, prodynorphin- and preprotachykinin-derived neuropeptides levels.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 67 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 121
Identifiers
urn:nbn:se:uu:diva-120303 (URN)978-91-554-7749-3 (ISBN)
Public defence
2010-04-28, B41, BMC, Husargatan 3, Uppsala, Sweden, 09:15 (English)
Opponent
Supervisors
Available from: 2010-04-06 Created: 2010-03-11 Last updated: 2011-05-05Bibliographically approved

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Rossbach, UweNilsson, AnnaKultima, KimZhou, QinHallberg, MathiasGordh, TorstenAndren, Per E.Nyberg, Fred

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Rossbach, UweNilsson, AnnaKultima, KimZhou, QinHallberg, MathiasGordh, TorstenAndren, Per E.Nyberg, Fred
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Biological Research on Drug DependenceDepartment of Pharmaceutical BiosciencesDepartment of Medical Sciences
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