title: Mesenchymal Stem Cell Transplantation Promotes Neurogenesis and Ameliorates Autism Related Behaviors in BTBR Mice.
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.
authors.affiliation: Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel- Aviv, Israel.
authors.forename: Hadar
authors.initials: H
authors.lastname: Segal-Gavish
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Golan
authors.initials: G
authors.lastname: Karvat
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Noy
authors.initials: N
authors.lastname: Barak
authors.affiliation: Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel- Aviv, Israel.|Geha Mental Health Center, Petah Tikva, Israel.
authors.forename: Ran
authors.initials: R
authors.lastname: Barzilay
authors.affiliation: Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel- Aviv, Israel.
authors.forename: Javier
authors.initials: J
authors.lastname: Ganz
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Liat
authors.initials: L
authors.lastname: Edry
authors.affiliation: Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel- Aviv, Israel.
authors.forename: Israel
authors.initials: I
authors.lastname: Aharony
authors.affiliation: Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel- Aviv, Israel.
authors.forename: Daniel
authors.initials: D
authors.lastname: Offen
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Tali
authors.initials: T
authors.lastname: Kimchi
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000503:physiopathology* / Q000628:therapy*; D001522:Behavior, Animal; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D008815:Mice, Inbred Strains; D055495:Neurogenesis / Q000502:physiology*; D011506:Proteins / Q000378:metabolism; D012919:Social Behavior; D013239:Stereotyped Behavior / Q000502:physiology*
chemical_list: D011506:Proteins
keywords: BDNF; BTBR; MSC; animal model; neurogenesis