Taurine Improved Autism-Like Behaviours and Defective Neurogenesis of the Hippocampus in BTBR Mice through the PTEN/mTOR/AKT Signalling Pathway

Folia Biol (Praha). 2024;70(1):45-52. doi: 10.14712/fb2024070010045.

Abstract

Effective treatment of patients with autism spectrum disorder (ASD) is still absent so far. Taurine exhibits therapeutic effects towards the autism-like behaviour in ASD model animals. Here, we determined the mechanism of taurine effect on hippocampal neurogenesis in genetically inbred BTBR T+ tf/J (BTBR) mice, a proposed model of ASD. In this ASD mouse model, we explored the effect of oral taurine supplementation on ASD-like behaviours in an open field test, elevated plus maze, marble burying test, self-grooming test, and three-chamber test. The mice were divided into four groups of normal controls (WT) and models (BTBR), who did or did not receive 6-week taurine supplementation in water (WT, WT+ Taurine, BTBR, and BTBR+Taurine). Neurogenesis-related effects were determined by Ki67 immunofluorescence staining. Western blot analysis was performed to detect the expression of phosphatase and tensin homologue deleted from chromosome 10 (PTEN)/mTOR/AKT pathway-associated proteins. Our results showed that taurine improved the autism-like behaviour, increased the proliferation of hippocampal cells, promoted PTEN expression, and reduced phosphorylation of mTOR and AKT in hippocampal tissue of the BTBR mice. In conclusion, taurine reduced the autism-like behaviour in partially inherited autism model mice, which may be associa-ted with improving the defective neural precursor cell proliferation and enhancing the PTEN-associated pathway in hippocampal tissue.

Keywords: ASD; Ki67; PTEN; hippocampal neurogenesis; taurine.

MeSH terms

  • Animals
  • Autism Spectrum Disorder / drug therapy
  • Autism Spectrum Disorder / metabolism
  • Autistic Disorder* / drug therapy
  • Autistic Disorder* / metabolism
  • Behavior, Animal / drug effects
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Hippocampus* / drug effects
  • Hippocampus* / metabolism
  • Mice
  • Neurogenesis* / drug effects
  • PTEN Phosphohydrolase* / drug effects
  • PTEN Phosphohydrolase* / metabolism
  • Proto-Oncogene Proteins c-akt* / drug effects
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Signal Transduction* / drug effects
  • TOR Serine-Threonine Kinases* / drug effects
  • TOR Serine-Threonine Kinases* / metabolism
  • Taurine* / pharmacology

Substances

  • mTOR protein, mouse
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • Pten protein, mouse
  • Taurine
  • TOR Serine-Threonine Kinases