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J Neuroinflammation. 2014 Nov 19;11:189. doi: 10.1186/s12974-014-0189-0.

GABAergic/glutamatergic imbalance relative to excessive neuroinflammation in autism spectrum disorders.

El-Ansary A1,2,3,4, Al-Ayadhi L5,6,7.

Author information

1
Biochemistry Department, Science College, King Saud University, PO box 22452, 11495, Riyadh, Saudi Arabia. elansary@ksu.edu.sa.
2
Autism Research and Treatment Center, Riyadh, Saudi Arabia. elansary@ksu.edu.sa.
3
Shaik Al-Amodi Autism Research Chair, King Saud University, Riyadh, Saudi Arabia. elansary@ksu.edu.sa.
4
Medicinal Chemistry Department, National Research Center, Dokki, Cairo, Egypt. elansary@ksu.edu.sa.
5
Autism Research and Treatment Center, Riyadh, Saudi Arabia. ayadh2@gmail.com.
6
Shaik Al-Amodi Autism Research Chair, King Saud University, Riyadh, Saudi Arabia. ayadh2@gmail.com.
7
Department of Physiology, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia. ayadh2@gmail.com.

Abstract

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.

PMID:
25407263
PMCID:
PMC4243332
DOI:
10.1186/s12974-014-0189-0
[Indexed for MEDLINE]
Free PMC Article

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