The expression of retinoic acid receptor alpha is increased in the granule cells of the dentate gyrus in schizophrenia

Psychiatry Res. 2005 Jan 30;133(1):13-21. doi: 10.1016/j.psychres.2004.11.003.

Abstract

Mounting evidence suggests that schizophrenia is a neurodevelopmental disease resulting in dysfunctional connectivity between various brain regions. Retinoid pathway dysregulation has been proposed as a potentially important factor in the etiology of schizophrenia. Retinoid signaling plays a central role in many aspects of development, ranging from neurogenesis to activity-dependent plasticity, and regulates the expression of many candidate genes for schizophrenia. The retinoid pathway acts through two families of nuclear receptors highly expressed in the hippocampus, the retinoic acid (RAR) and retinoid X (RXR) receptors, both existing in three different subtypes (alpha, beta and gamma) and several isoforms. The present study examines the expression of the retinoid receptors in the dentate gyrus of schizophrenia and nonpsychiatric controls. The proportion of granule cells of the dentate gyrus expressing RAR(alpha) is increased by twofold in schizophrenia, while the proportion of cells expressing RAR(gamma)1 and 2, as well as RXR(beta) and gamma, is unchanged. These results demonstrate a dysregulation in the expression of at least one member of the RAR family of retinoid receptors in schizophrenia. Understanding the basis for this and how it affects downstream molecular pathways associated with hippocampal plasticity may provide insight into the dysfunctional connectivity of schizophrenia.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Age Factors
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Autopsy
  • Dentate Gyrus / cytology
  • Dentate Gyrus / metabolism*
  • Female
  • Gene Expression* / genetics
  • Hippocampus / metabolism
  • Hippocampus / physiopathology
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neural Pathways / metabolism
  • Neural Pathways / physiopathology
  • Neuronal Plasticity / genetics
  • Neurons / metabolism*
  • Receptors, Retinoic Acid / genetics*
  • Receptors, Retinoic Acid / metabolism
  • Receptors, Retinoic Acid / physiology
  • Retinoic Acid Receptor alpha
  • Retinoid X Receptors / genetics
  • Retinoid X Receptors / metabolism
  • Retinoid X Receptors / physiology
  • Schizophrenia / genetics
  • Schizophrenia / metabolism*
  • Schizophrenia / physiopathology

Substances

  • RARA protein, human
  • Receptors, Retinoic Acid
  • Retinoic Acid Receptor alpha
  • Retinoid X Receptors