Abnormal hippocampal neurogenesis and impaired social recognition memory in two neurodevelopmental models of schizophrenia

FASEB J. 2024 Nov 15;38(21):e70138. doi: 10.1096/fj.202401258RR.

Abstract

Schizophrenia is a mental disorder characterized by cognitive impairments, specifically deficits in social recognition memory (SRM). Abnormal hippocampal neurogenesis has been implicated in these deficits. Due to the pathogenetic heterogeneity of schizophrenia, studying the hippocampal neurogenesis and SRM in two models with prenatal and postnatal defects could enhance our understanding of the developmental aspects of the biological susceptibility to schizophrenia. Here, we examined SRM and hippocampal neurogenesis in two developmental models of schizophrenia: gestational exposure to methylazoxymethanol acetate (MAM) and postweaning social isolation (SI). Our findings revealed that gestational MAM exposure induced a decay of social memory while postweaning SI led to impaired social memory formation and decay. In both models, we observed a correlation between impaired SRM and reduced number, and abnormal differentiation and less complex morphology of hippocampal neurons. These results indicate that aberrant hippocampal neurogenesis may contribute to the deficits of SRM in both models, and these abnormalities may be a shared underlying pathogenic factor in developmental models of schizophrenia, regardless of prenatal and postnatal pathogenesis.

Keywords: heterogeneity; neurodevelopment; neurogenesis; schizophrenia; social recognition memory.

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Female
  • Hippocampus* / pathology
  • Male
  • Memory / physiology
  • Methylazoxymethanol Acetate* / analogs & derivatives
  • Methylazoxymethanol Acetate* / toxicity
  • Neurogenesis*
  • Neurons / metabolism
  • Neurons / pathology
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Rats
  • Recognition, Psychology / physiology
  • Schizophrenia* / pathology
  • Schizophrenia* / physiopathology
  • Social Isolation

Substances

  • Methylazoxymethanol Acetate