29845
Autistic Phenotype in the N-Ethylmaleimide Sensitive Factor Gene Lacking Mice
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.