Potential of GRID2 receptor gene for preventing TNF-induced neurodegeneration in autism


Kalkan Z., Durasi I. M. , SEZERMAN O. U. , Atasever-Arslan B.

NEUROSCIENCE LETTERS, vol.620, pp.62-69, 2016 (SCI-Expanded) identifier identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 620
  • Publication Date: 2016
  • Doi Number: 10.1016/j.neulet.2016.03.043
  • Journal Name: NEUROSCIENCE LETTERS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.62-69
  • Keywords: SH-SY5Y human neuroblastoma cells, Autism, ASD, TIVF-alpha, GRID2, SPECTRUM DISORDERS, NERVOUS-SYSTEM, GLUTAMATE, ACTIVATION, EXPERIENCE, DIAGNOSIS, CASPASE-3, BRAIN
  • Acibadem Mehmet Ali Aydinlar University Affiliated: Yes

Abstract

Autism is one of the most common subtypes of autism spectrum disorder (ASD). Recent studies suggested a relationship between immune-dependent coding genes and ASD, indicating that long term neuroimmunological anomalies affect brain development and synaptic transmission among neural networks. Furthermore, various studies focused on biomarker potential of TNF-alpha in autism. Ionotropic receptors are also studied as potential marker for autism since altered gene expression levels are observed in autistic patients. GRID2 is a candidate ionotropic receptor which is involved glutamate transfer. In this study, to propose TNF-alpha dependent cellular processes involved in autism aetiology in relation to GRID2 we performed a bioinformatic network analysis and identified potential pathways and genes that are involved in TNF-alpha induced changes at GRID2 receptor levels. As a result, we ascertained the GRID2 receptor gene as a candidate gene and further studied the association between GRID2 expression levels and TNF-induced neurodegeneration. Our bioinformatic analyses and experimental results revealed that TNF-alpha regulates GRID2 gene expression by activating Cdc42 and GOPC genes. Moreover, increased TNF-alpha levels leads to increase of caspase-3 protein levels triggering neuronal apoptosis leading to neuronal deficiency, which is one of the major symptoms of autism. The study is the first to show the role of TNF-alpha in regulation of GRID2 gene expression and its signalling pathway. As a result, GRID2 gene can be a suppressor in TNF-induced neurodegeneration which may help to understand the main factors leading to autism. (C) 2016 Elsevier Ireland Ltd. All rights reserved.