We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Autistic-Like Behavior and Impairment of Serotonin Transporter and AMPA Receptor Trafficking in N -Ethylmaleimide Sensitive Factor Gene-Deficient Mice.
- Authors
Xie, Min-Jue; Iwata, Keiko; Ishikawa, Yasuyuki; Nomura, Yuki; Tani, Tomomi; Murata, Koshi; Fukazawa, Yugo; Matsuzaki, Hideo
- Abstract
Autism spectrum disorder (ASD), characterized by profound impairment in social interactions and communication skills, is the most common neurodevelopmental disorder. Many studies on the mechanisms underlying the development of ASD have focused on the serotonergic system; however, these studies have failed to completely elucidate the mechanisms. We previously identified N -ethylmaleimide-sensitive factor (NSF) as a new serotonin transporter (SERT)-binding protein and described its importance in SERT membrane trafficking and uptake in vitro. In the present study, we generated Nsf +/- mice and investigated their behavioral, neurotransmitter, and neurophysiological phenotypes in vivo. Nsf +/- mice exhibited abnormalities in sociability, communication, repetitiveness, and anxiety. Additionally, Nsf loss led to a decrease in membrane SERT expression in the raphe and accumulation of glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors at the synaptic membrane surface in the hippocampal CA1 region. We found that postsynaptic density and long-term depression were impaired in the hippocampal CA1 region of Nsf +/- mice. Taken together, these findings demonstrate that NSF plays a role in synaptic plasticity and glutamatergic and serotonergic systems, suggesting a possible mechanism by which the gene is linked to the pathophysiology of autistic behaviors.
- Subjects
SEROTONIN transporters; AMPA receptors; AUTISM spectrum disorders; SEROTONIN receptors; PROPIONIC acid; MICE
- Publication
Frontiers in Genetics, 2021, Vol 12, p1
- ISSN
1664-8021
- Publication type
Article
- DOI
10.3389/fgene.2021.748627