Mesenchymal Stem Cell Transplantation Promotes Neurogenesis and Ameliorates Autism Related Behaviors in BTBR Mice

Hadar Segal-Gavish, Golan Karvat, Noy Barak, Ran Barzilay, Javier Ganz, Liat Edry, Israel Aharony, Daniel Offen*, Tali Kimchi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Autism spectrum disorders (ASD) are characterized by social communication deficits, cognitive rigidity, and repetitive stereotyped behaviors. Mesenchymal stem cells (MSC) have a paracrine regenerative effect, and were speculated to be a potential therapy for ASD. The BTBR inbred mouse strain is a commonly used model of ASD as it demonstrates robust behavioral deficits consistent with the diagnostic criteria for ASD. BTBR mice also exhibit decreased brain-derived neurotrophic factor (BDNF) signaling and reduced hippocampal neurogenesis. In the current study, we evaluated the behavioral and molecular effects of intracerebroventricular MSC transplantation in BTBR mice. Transplantation of MSC resulted in a reduction of stereotypical behaviors, a decrease in cognitive rigidity and an improvement in social behavior. Tissue analysis revealed elevated BDNF protein levels in the hippocampus accompanied by increased hippocampal neurogenesis in the MSC-transplanted mice compared with sham treated mice. This might indicate a possible mechanism underpinning the behavioral improvement. Our study suggests a novel therapeutic approach which may be translatable to ASD patients in the future.

Original languageEnglish
Pages (from-to)17-32
Number of pages16
JournalAutism Research
Volume9
Issue number1
DOIs
StatePublished - 1 Jan 2016

Keywords

  • Animal model
  • BDNF
  • BTBR
  • MSC
  • Neurogenesis

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