Cellular Models in Schizophrenia Research

Int J Mol Sci. 2021 Aug 7;22(16):8518. doi: 10.3390/ijms22168518.

Abstract

Schizophrenia (SZ) is a prevalent functional psychosis characterized by clinical behavioural symptoms and underlying abnormalities in brain function. Genome-wide association studies (GWAS) of schizophrenia have revealed many loci that do not directly identify processes disturbed in the disease. For this reason, the development of cellular models containing SZ-associated variations has become a focus in the post-GWAS research era. The application of revolutionary clustered regularly interspaced palindromic repeats CRISPR/Cas9 gene-editing tools, along with recently developed technologies for cultivating brain organoids in vitro, have opened new perspectives for the construction of these models. In general, cellular models are intended to unravel particular biological phenomena. They can provide the missing link between schizophrenia-related phenotypic features (such as transcriptional dysregulation, oxidative stress and synaptic dysregulation) and data from pathomorphological, electrophysiological and behavioural studies. The objectives of this review are the systematization and classification of cellular models of schizophrenia, based on their complexity and validity for understanding schizophrenia-related phenotypes.

Keywords: CRISPR/Cas9; cell lines; model validity; multicellular models; schizophrenia.

Publication types

  • Review

MeSH terms

  • Biomedical Research
  • CRISPR-Cas Systems*
  • Gene Editing*
  • Gene Expression Regulation*
  • Genome-Wide Association Study
  • Humans
  • Models, Neurological*
  • Schizophrenia* / genetics
  • Schizophrenia* / metabolism