Potential of olfactory neuroepithelial cells as a model to study schizophrenia: A focus on GPCRs (Review)

Int J Mol Med. 2024 Jan;53(1):7. doi: 10.3892/ijmm.2023.5331. Epub 2023 Dec 1.

Abstract

Schizophrenia (SZ) is a multifactorial disorder characterized by volume reduction in gray and white matter, oxidative stress, neuroinflammation, altered neurotransmission, as well as molecular deficiencies such as punctual mutation in Disrupted‑in‑Schizophrenia 1 protein. In this regard, it is essential to understand the underlying molecular disturbances to determine the pathophysiological mechanisms of the disease. The signaling pathways activated by G protein‑coupled receptors (GPCRs) are key molecular signaling pathways altered in SZ. Convenient models need to be designed and validated to study these processes and mechanisms at the cellular level. Cultured olfactory stem cells are used to investigate neural molecular and cellular alterations related to the pathophysiology of SZ. Multipotent human olfactory stem cells are undifferentiated and express GPCRs involved in numerous physiological functions such as proliferation, differentiation and bioenergetics. The use of olfactory stem cells obtained from patients with SZ may identify alterations in GPCR signaling that underlie dysfunctional processes in both undifferentiated and specialized neurons or derived neuroglia. The present review aimed to analyze the role of GPCRs and their signaling in the pathophysiology of SZ. Culture of olfactory epithelial cells constitutes a suitable model to study SZ and other psychiatric disorders at the cellular level.

Keywords: G protein‑coupled receptor; dopamine; glutamate; human neural stem cell; olfactory epithelium; schizophrenia; serotonin.

Publication types

  • Review

MeSH terms

  • Humans
  • Neuroepithelial Cells / metabolism
  • Neurons / metabolism
  • Receptors, G-Protein-Coupled
  • Schizophrenia* / genetics
  • Schizophrenia* / metabolism
  • Stem Cells / metabolism

Substances

  • Receptors, G-Protein-Coupled

Grants and funding

The present study was supported by Consejo Nacional de Humanidades Ciencia y Tecnología (grant no. CF/2019/137725) and Programa Presupuestario F003 (grant no. 287115).