University of Sussex
Browse

File(s) not publicly available

Sp1 and NFkappaB pathways are regulated in brain in response to acute and chronic ethanol

journal contribution
posted on 2023-06-07, 13:37 authored by S L Rulten, Tamzin Ripley, C L Hunt, D N Stephens, L V Mayne
DNA microarray analysis was used to identify candidate ethanol-regulated genes, as a first step towards exploring how transcriptional changes might lead to ethanol-induced changes in behaviour. Mice were treated with a single acute intraperitoneal ethanol dose and DNA microarray analysis performed on midbrain 2 h posttreatment. We predicted that if ethanol-regulated genes contribute towards behaviour, then constitutive variation in brain expression levels may also contribute to strain-specific differences in ethanol-related behaviour of inbred mouse strains. On the basis of this assumption, we interrogated the BXD inbred strain phenotype database and the U74Av2 MAS5 brain expression database using the WebQTL tool (http://www.genenetwork.org/) and correlated ethanol-related behaviours to expression levels. Constitutive expression levels of 70/90 candidate genes, identified from the DNA microarray analysis, varied significantly between inbred strains and correlated significantly with strain-specific differences in ethanol-related behaviours. These genes were then mapped onto biochemical pathways using Stratagene's PathwayAssist software. This analysis identified the transcription factor Sp1 and NFkappaB pathways in the acute response to ethanol. Ethanol regulation of Sp1 transcription was conserved between humans and mouse. As predicted, downstream targets of Sp1 were also ethanol regulated. NFkappaBia, an important regulator of NFkappaB function and Rela, an NFkappaB-binding partner, were both regulated by ethanol. Expression of both Sp1 and NFkappaBialpha were also downregulated following chronic ethanol treatment. As Sp1 and NFkappaB are implicated in plasticity and behaviour, our data suggest a role for these transcription factors in the long-term behavioural adaptations to ethanol.

History

Publication status

  • Published

Journal

Genes, Brain and Behavior

ISSN

1601-1848

Publisher

Blackwell Publishing

Issue

3

Volume

5

Page range

257-273

Department affiliated with

  • Biochemistry Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2006-12-11

Usage metrics

    University of Sussex (Publications)

    Categories

    No categories selected

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC