Fullerenols Ameliorate Social Deficiency and Rescue Cognitive Dysfunction of BTBR T+Itpr3tf/J Autistic-Like Mice

Int J Nanomedicine. 2024 Jun 17:19:6035-6055. doi: 10.2147/IJN.S459511. eCollection 2024.

Abstract

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that affects social interaction and communication and can cause stereotypic behavior. Fullerenols, a type of carbon nanomaterial known for its neuroprotective properties, have not yet been studied for their potential in treating ASD. We aimed to investigate its role in improving autistic behaviors in BTBR T+Itpr3tf/J (BTBR) mice and its underlying mechanism, which could provide reliable clues for future ASD treatments.

Methods: Our research involved treating C57BL/6J (C57) and BTBR mice with either 0.9% NaCl or fullerenols (10 mg/kg) daily for one week at seven weeks of age. We then conducted ASD-related behavioral tests in the eighth week and used RNA-seq to screen for vital pathways in the mouse hippocampus. Additionally, we used real-time quantitative PCR (RT-qPCR) to verify related pathway genes and evaluated the number of stem cells in the hippocampal dentate gyrus (DG) by Immunofluorescence staining.

Results: Our findings revealed that fullerenols treatment significantly improved the related ASD-like behaviors of BTBR mice, manifested by enhanced social ability and improved cognitive deficits. Immunofluorescence results showed that fullerenols treatment increased the number of DCX+ and SOX2+/GFAP+ cells in the DG region of BTBR mice, indicating an expanded neural progenitor cell (NPC) pool of BTBR mice. RNA-seq analysis of the mouse hippocampus showed that VEGFA was involved in the rescued hippocampal neurogenesis by fullerenols treatment.

Conclusion: In conclusion, our findings suggest that fullerenols treatment improves ASD-like behavior in BTBR mice by upregulating VEGFA, making nanoparticle- fullerenols a promising drug for ASD treatment.

Keywords: BTBR; autism spectrum disorder; fullerenols; hippocampus; neurogenesis.

MeSH terms

  • Animals
  • Autism Spectrum Disorder* / drug therapy
  • Autistic Disorder / drug therapy
  • Behavior, Animal / drug effects
  • Cognitive Dysfunction* / drug therapy
  • Disease Models, Animal*
  • Doublecortin Protein*
  • Fullerenes* / chemistry
  • Fullerenes* / pharmacology
  • Hippocampus / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • Neurogenesis / drug effects
  • Neuroprotective Agents / pharmacology
  • Social Behavior
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Fullerenes
  • Dcx protein, mouse
  • fullerenol
  • Doublecortin Protein
  • Vascular Endothelial Growth Factor A
  • Neuroprotective Agents

Grants and funding

This study was supported by the National Nature Science Foundation of China (No. 82071544). Innovation Research Group at Institutions of Higher Education in Chongqing (CXQT19010). Student’s Platform for Innovation and Entrepreneurship Training Program (202390035015).