18581
Abnormal Expression of a SERT-Binding Protein, NSF, in Autism: Implications for Pathophysiology in Autism
Saturday, May 16, 2015: 11:30 AM-1:30 PM
Imperial Ballroom (Grand America Hotel)
K. Iwata1, H. Matsuzaki2, K. Nakamura3, T. Katayama4 and N. Mori5, (1)Research Center for Child Mental Development, Fukui Univ., Fukui, Japan, (2)Research Center for Child Mental Development, University of Fukui, Fukui, Japan, (3)Department of Neuropsychiatry, Graduate School of Medicine, Hirosaki University, Hirosaki, Japan, (4)Osaka University United Graduate School of Child Development, Suita, Japan, (5)Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan
Background: Change in serotonin transporter (SERT) function has been implicated in autism. SERT function is influenced by the number of transporter molecules present at the cell surface, which is regulated by various cellular mechanisms including interactions with other proteins. Thus, we searched for novel SERT-binding proteins and investigated. As we presented at the IMFAR 2014,
N-ethylmaleimide-sensitive factor (NSF) was identified as a novel SERT-binding protein. NSF co-localized with SERT at the plasma membrane, and NSF knockdown resulted in decreased SERT expression at the cell membranes and its uptake function in HEK293-hSERT cells. In addition, NSF endogenously co-localized with SERT and interacted with SERT in mouse brain.
Objectives: The objectives of this study were to address whether expressions of SERT and NSF were changed in autism and whether these expression correlate with clinical variables and symptom profiles.
Methods: We examined the mRNA expression of SERT (SLC6A4) and NSF in the post-mortem brains from 7 subjects with autism and 11 healthy age- and sex-matched control subjects, and in the lymphocytes from 30 male subjects with autism and 30 male healthy age-matched control subjects by quantitative real-time PCR. Additionally, we evaluated the relationships between these expression levels and clinical variables and symptom profiles.
Results: While SLC6A4 expression was not significantly changed, NSF expression tended to be reduced in post-mortem brains, however this potential trend is not statistically significant, and was significantly reduced and correlated with the severity of the clinical symptom in lymphocytes of subjects with autism.
Conclusions: A possible role for NSF in the pathophysiology of autism, through modulation of SERT trafficking, is suggested.
