uu.seUppsala universitets publikasjoner
Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Nandrolone-induced hippocampal phosphorylation of NMDA receptor subunits and ERKs
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap, Avdelningen för biologisk beroendeforskning.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap, Avdelningen för biologisk beroendeforskning.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap, Avdelningen för biologisk beroendeforskning.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. (Lindholm)
2007 (engelsk)Inngår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 357, nr 4, s. 1028-1033Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The age-related decline in gonadal steroids is associated with changes in mood and memory function. It appears that normal physiological concentrations of the steroids are required for adequate synaptic plasticity. However, the effects of high levels of androgens subsequent to misuse of anabolic androgenic steroids (AAS) are largely unknown. In this study, rats were given i.m. nandrolone as a single dose or daily for 14 days and the effects on synaptic components in hippocampal synaptoneurosomes were measured 24h after the last injection. Western blot analysis revealed that a single injection of AAS increased phosphorylation of the NMDA receptor subunits NR2A and NR2B and ERK1/2, while the levels of phosphorylated CaMKIIalpha were unaltered. No changes were seen in other synaptic proteins tested, i.e., BDNF, Arc, TUC-4, and beta-tubulin III. Daily administration of nandrolone for 2 weeks did not affect the content of any of the proteins tested. From this in vivo study, it is concluded that important synaptic components respond to a single high dose of nandrolone, an effect that may influence synapse function.

sted, utgiver, år, opplag, sider
2007. Vol. 357, nr 4, s. 1028-1033
Emneord [en]
Anabolic androgenic steroids, Nandrolone, Phosphorylation, ERK, NMDA receptor subunits, Hippocampus, Rat, Western blot
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-11166DOI: 10.1016/j.bbrc.2007.04.037ISI: 000246648400033PubMedID: 17451646OAI: oai:DiVA.org:uu-11166DiVA, id: diva2:38934
Tilgjengelig fra: 2008-01-18 Laget: 2008-01-18 Sist oppdatert: 2018-01-12bibliografisk kontrollert
Inngår i avhandling
1. The Impact of Drugs of Abuse on the Neuroproteome: Application of Immunoblotting and LC-MS-based Proteomics
Åpne denne publikasjonen i ny fane eller vindu >>The Impact of Drugs of Abuse on the Neuroproteome: Application of Immunoblotting and LC-MS-based Proteomics
2010 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
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.

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis, 2010. s. 67
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 121
Identifikatorer
urn:nbn:se:uu:diva-120303 (URN)978-91-554-7749-3 (ISBN)
Disputas
2010-04-28, B41, BMC, Husargatan 3, Uppsala, Sweden, 09:15 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2010-04-06 Laget: 2010-03-11 Sist oppdatert: 2011-05-05bibliografisk kontrollert

Open Access i DiVA

Fulltekst mangler i DiVA

Andre lenker

Forlagets fulltekstPubMed

Personposter BETA

Rossbach, Uwe L. W.Le Grevès, Pierre

Søk i DiVA

Av forfatter/redaktør
Rossbach, Uwe L. W.Le Grevès, Pierre
Av organisasjonen
I samme tidsskrift
Biochemical and Biophysical Research Communications - BBRC

Søk utenfor DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric

doi
pubmed
urn-nbn
Totalt: 469 treff
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf