Autistic Phenotype in the N-Ethylmaleimide Sensitive Factor Gene Lacking Mice

Poster Presentation
Friday, May 3, 2019: 11:30 AM-1:30 PM
Room: 710 (Palais des congres de Montreal)
M. J. Xie1,2, K. Iwata1,2, Y. Ishikawa3, Y. Fukazawa1,4 and H. Matsuzaki1,2, (1)Research Center for Child Mental Development, University of Fukui, Fukui, Japan, (2)United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Osaka, Japan, (3)Department of Systems Life Engineering, Maebashi Institute of Technology, Maebashi, Japan, (4)Division of Brain Structures and function, Department of Morphological and Physiological Sciences, Graduate School of Medical Sciences, University of Fukui, Fukui, Japan
Background: Autism, characterized by profound impairment in social interactions and communicative skills, is the most common neurodevelopmental disorder. Many studies on the mechanisms of autism have focused on the serotonergic system but its underlying molecular mechanisms remain controversial. In our previous report, we reidentified N-ethylmaleimide-sensitive factor (NSF) as new serotonin transporter (SERT) binding protein (Iwata et al 2014).

Objectives: In this study, we generated the NSF+/- mice and investigated their phenotypes.

Methods: As previous report has already shown that NSF is necessary for AMPA-type ionotropic glutamate receptors (AMPARs) location in the synapse, we examined SERT and AMPAR location in the synapse of the NSF+/- mice by using freeze-fractured replica-immunolabeling study at first. In next, we assessed behavioral test including the social interaction behaviors by the three-chambered task and the social communication by ultrasonic vocalizations. Finally, we examined whether hippocampal long-term depression (LTD) deficits can be restored in the NSF+/- mice for checking the excitatory/inhibitory (E/I) synaptic balance.

Results: We found the membrane expression of SERT half-reduced in the raphe and the significant decrease in postsynaptic expression of AMPAR in CA1 of the hippocampus of the NSF+/- mice, compared with wild mice. Then, we found that the spending time near the chamber with a newly introduced mouse (stranger), were significantly reduced in the NSF+/- mice, and found that the ultrasonic vocalizations significantly reduced in the NSF+/- mice, compared with wild mice respectively. Field electrophysiology performed on brain slices confirmed that NSF gene lacking significantly reduced dorsal CA1 hippocampal LTD in mice.

Conclusions: The present results suggest that cellular trafficking turbulence of synaptic molecules by lacking NSF gene might be related to the pathophysiology of autistic properties.

See more of: Animal Models
See more of: Animal Models