GABAergic/glutamatergic imbalance relative to excessive neuroinflammation in autism spectrum disorders | Journal of Neuroinflammation | Full Text

Background Autism spectrum disorder (ASD) is characterized by three core behavioral domains: social deficits, impaired communication, and repetitive behaviors. Glutamatergic/GABAergic imbalance has been found in various preclinical models of ASD. Additionally, autoimmunity immune dysfunction, and neuroinflammation are also considered as etiological mechanisms of this disorder. This study aimed to elucidate the relationship between glutamatergic/ GABAergic imbalance and neuroinflammation as two recently-discovered autism-related etiological mechanisms. Methods Twenty autistic patients aged 3 to 15 years and 19 age- and gender-matched healthy controls were included in this study. The plasma levels of glutamate, GABA and glutamate/GABA ratio as markers of excitotoxicity together with TNF-α, IL-6, IFN-γ and IFI16 as markers of neuroinflammation were determined in both groups. Results Autistic patients exhibited glutamate excitotoxicity based on a much higher glutamate concentration in the autistic patients than in the control subjects. Unexpectedly higher GABA and lower glutamate/GABA levels were recorded in autistic patients compared to control subjects. TNF-α and IL-6 were significantly lower, whereas IFN-γ and IFI16 were remarkably higher in the autistic patients than in the control subjects. Conclusion Multiple regression analysis revealed associations between reduced GABA level, neuroinflammation and glutamate excitotoxicity. This study indicates that autism is a developmental synaptic disorder showing imbalance in GABAergic and glutamatergic synapses as a consequence of neuroinflammation.

GABAergic/glutamatergic imbalance relative to excessive neuroinflammation in autism spectrum disorders Research article Open access Published: 19 November 2014 Volume 11 , article number 189 ( 2014 ) Cite this article You have full access to this open access article Download PDF Save article View saved research Journal of Neuroinflammation Aims and scope Submit manuscript GABAergic/glutamatergic imbalance relative to excessive neuroinflammation in autism spectrum disorders Download PDF Abstract Background Autism spectrum disorder (ASD) is characterized by three core behavioral domains: social

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