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, Marin D Veldic, D. R. Grayson, A. Guidotti

Research output: Contribution to journalArticle

129 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Schizophrenia
Genes
Genome
Dendritic Spines
Brain
Neurologic Mutant Mice
Post-Synaptic Density
Neuronal Plasticity
Histone Deacetylase Inhibitors
Pyramidal Cells
Interneurons
Dendrites
Gene expression
Integrins
Neurons
Extracellular Matrix
Plasticity
Down-Regulation
Gene Expression
Acids

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacy
  • Molecular Medicine

Cite this

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

REELIN and schizophrenia : a disease at the interface of the genome and the epigenome. / Costa, E.; Chen, Y.; Davis, J.; Dong, E.; Noh, J. S.; Tremolizzo, L.; Veldic, Marin D; Grayson, D. R.; Guidotti, A.

In: Molecular Interventions, Vol. 2, No. 1, 02.2002, p. 47-57.

Research output: Contribution to journalArticle

Costa, E, Chen, Y, Davis, J, Dong, E, Noh, JS, Tremolizzo, L, Veldic, MD, Grayson, DR & Guidotti, A 2002, 'REELIN and schizophrenia: a disease at the interface of the genome and the epigenome.', Molecular Interventions, vol. 2, no. 1, pp. 47-57.
Costa E, Chen Y, Davis J, Dong E, Noh JS, Tremolizzo L et al. REELIN and schizophrenia: a disease at the interface of the genome and the epigenome. Molecular Interventions. 2002 Feb;2(1):47-57.
Costa, E. ; Chen, Y. ; Davis, J. ; Dong, E. ; Noh, J. S. ; Tremolizzo, L. ; Veldic, Marin D ; Grayson, D. R. ; Guidotti, A. / REELIN and schizophrenia : a disease at the interface of the genome and the epigenome. In: Molecular Interventions. 2002 ; Vol. 2, No. 1. pp. 47-57.
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