The Cerebellum

, Volume 8, Issue 3, pp 366–372

Increase in Cerebellar Neurotrophin-3 and Oxidative Stress Markers in Autism

Authors

    • Department of PsychiatryHarvard Medical School
    • Department of PsychiatryBrigham and Women’s Hospital
  • Ming Xu
    • Department of Integrative Physiology, Graduate School of MedicineGunma University
  • Noriyuki Koibuchi
    • Department of Integrative Physiology, Graduate School of MedicineGunma University
Article

DOI: 10.1007/s12311-009-0105-9

Cite this article as:
Sajdel-Sulkowska, E.M., Xu, M. & Koibuchi, N. Cerebellum (2009) 8: 366. doi:10.1007/s12311-009-0105-9

Abstract

Autism is a neurodevelopmental disorder characterized by social and language deficits, ritualistic–repetitive behaviors and disturbance in motor functions. Data of imaging, head circumference studies, and Purkinje cell analysis suggest impaired brain growth and development. Both genetic predisposition and environmental triggers have been implicated in the etiology of autism, but the underlying cause remains unknown. Recently, we have reported an increase in 3-nitrotyrosine (3-NT), a marker of oxidative stress damage to proteins in autistic cerebella. In the present study, we further explored oxidative damage in the autistic cerebellum by measuring 8-hydroxydeoxyguanosine (8-OH-dG), a marker of DNA modification, in a subset of cases analyzed for 3-NT. We also explored the hypothesis that oxidative damage in autism is associated with altered expression of brain neurotrophins critical for normal brain growth and differentiation. The content of 8-OH-dG in cerebellar DNA isolated by the proteinase K method was measured using an enzyme-linked immunosorbent assay (ELISA); neurotrophin-3 (NT-3) levels in cerebellar homogenates were measured using NT-3 ELISA. Cerebellar 8-OH-dG showed trend towards higher levels with the increase of 63.4% observed in autism. Analysis of cerebellar NT-3 showed a significant (p = 0.034) increase (40.3%) in autism. Furthermore, there was a significant positive correlation between cerebellar NT-3 and 3-NT (r = 0.83; p = 0.0408). These data provide the first quantitative measure of brain NT-3 and show its increase in the autistic brain. Altered levels of brain NT-3 are likely to contribute to autistic pathology not only by affecting brain axonal targeting and synapse formation but also by further exacerbating oxidative stress and possibly contributing to Purkinje cell abnormalities.

Keywords

Oxidative stress8-OH-dG3-nitrotyrosine (3-NT)Neurotrophin-3 (NT-3)AutismCerebellum

Copyright information

© Springer Science+Business Media, LLC 2009