Epothilone D Modulate Autism-like Behaviors In The BTBR Mouse Model Of Autism

Objective:In this study,we evaluate whether Epothilone D is sufficient to modulate the autism-like behaviors on the BTBR mice,and study the underlying mechanism.Methods:1.Eight-week-old BTBR mice were treated with Epothilone D(3mg/kg)or DMSO once weekly for 8 weeks period.2.The mice were tested for social ability and repeated behavior immediately after the intraperitoneal injection.And when the behavioral tests were finished,the cerebral cortex of the mice was taken for Western blot and immunofluorescence staining.3.Chamber time,time spent sniffing the novel object versus the stranger mouse,and the entries to the side chambers in the social approach test were conducted by twoway ANOVA analysis.Comparing the time of self-grooming,and the data of Western blot and immunofluorescence staining,unpaired t-test were used.Results:1.Microtubule-stabilizing agents Epothilone D reduced the self-grooming times and increased social ability in BTBR mice.2.Microtubule-stabilizing agents Epothilone D improved microtubule's stability.3.Microtubule-stabilizing agents Epothilone D increased the the number of excitatory synapses and MBP expression in the cortex of BTBR mouse.Conclusion:This study showed that microtubule-stabilizing agents Epothilone D could modulate autism-like behaviors,possibly through changing the stability of microtubules and then increased the number of excitatory synapses and myelin proteins.Our findings suggest that Epothilone D may have selective therapeutic efficacy in treating abnormal social behaviors in autism.