REELIN and schizophrenia: a disease at the interface of the genome and the epigenome.

E. Costa, Y. Chen, J. Davis, E. Dong, J. S. Noh, L. Tremolizzo, M. Veldic, D. R. Grayson, A. Guidotti

Research output: Contribution to journalReview article

133 Scopus citations

Abstract

The downregulation of the Reelin gene (RELN) that occurs in schizophrenic brains, which are characterized by pyramidal neurons with shortened dendrites and by reduced expression densities of dendritic spines, may well result from hypermethylation of the RELN promoter. In the adult mammalian brain, gamma-aminoburytic acid-secreting (GABAergic) interneurons release RELN into the extracellular matrix, where it binds with high affinity to the integrin receptors present at dendritic spine postsynaptic densities and likely plays a role, elaborated in this article, in synaptic plasticity. In heterozygous reeler mice, which are haploinsufficient in RELN, inhibitors of histone deacetylase increase DNA demethylase activity and restore RELN expression. Such inhibitors could thus be of therapeutic value in mitigating vulnerability to schizophrenia among high-risk individuals.

Original languageEnglish (US)
Pages (from-to)47-57
Number of pages11
JournalMolecular interventions
Volume2
Issue number1
StatePublished - Feb 2002

ASJC Scopus subject areas

  • Molecular Medicine

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  • Cite this

    Costa, E., Chen, Y., Davis, J., Dong, E., Noh, J. S., Tremolizzo, L., Veldic, M., Grayson, D. R., & Guidotti, A. (2002). REELIN and schizophrenia: a disease at the interface of the genome and the epigenome. Molecular interventions, 2(1), 47-57.