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Impaired lipid metabolism markers to assess the risk of neuroinflammation in autism spectrum disorder

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Abstract

Autism spectrum disorder (ASD) is a multifactorial disorder caused by an interaction between environmental risk factors and a genetic background. It is characterized by impairment in communication, social interaction, repetitive behavior, and sensory processing. The etiology of ASD is still not fully understood, and the role of neuroinflammation in autism behaviors needs to be further investigated. The aim of the present study was to test the possible association between prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1), prostaglandin PGE2 EP2 receptors and nuclear kappa B (NF-κB) and the severity of cognitive disorders, social impairment, and sensory dysfunction. PGE2, COX-2, mPGES-1, PGE2-EP2 receptors and NF-κB as biochemical parameters related to neuroinflammation were determined in the plasma of 47 Saudi male patients with ASD, categorized as mild to moderate and severe as indicated by the Childhood Autism Rating Scale (CARS) or the Social Responsiveness Scale (SRS) or the Short Sensory Profile (SSP) and compared to 46 neurotypical controls. The data indicated that ASD patients have remarkably higher levels of the measured parameters compared to neurotypical controls, except for EP2 receptors that showed an opposite trend. While the measured parameter did not correlate with the severity of social and cognitive dysfunction, PGE2, COX-2, and mPGES-1 were remarkably associated with the dysfunction in sensory processing. NF-κB was significantly increased in relation to age. Based on the discussed data, the positive correlation between PGE2, COX-2, and mPGES-1 confirm the role of PGE2 pathway and neuroinflammation in the etiology of ASD, and the possibility of using PGE2, COX-2 and mPGES-1 as biomarkers of autism severity. NF-κB as inflammatory inducer showed an elevated level in plasma of ASD individuals. Receiver operating characteristic analysis together with predictiveness diagrams proved that the measured parameters could be used as predictive biomarkers of biochemical correlates to ASD.

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Abbreviations

AA :

Arachidonic acid

ASD :

Autism spectrum disorder

CARS :

Childhood autism rating scale

COX-2 :

Cyclooxygenase-2

cPLA2 :

Cytosolic phospholipase A2

GSH :

Glutathione

IFNγ :

Interferon gamma

IL-6 :

Interleukin-6

mPGES-1 :

Microsomal prostaglandin E synthase-1

NF-κB :

Nuclear factor kappa B

NMDA :

N-methyl-D-aspartate

PGE2 :

Prostaglandin E2

PGE2-EP2 :

Prostaglandin E2 EP2 receptors

PUFAs :

Polyunsaturated fatty acids

ROC-curve :

Receiver operating characteristics curve

ROS :

Reactive oxygen species

SRS :

Social responsiveness scale

SSP :

Short sensory profile

TNF-α :

Tumor necrosis factor alpha

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Acknowledgements

This research project was supported by a grant from the Research Center of the Center for Female Scientific and Medical Colleges at King Saud University, Riyadh, Saudi Arabia.

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Authors and Affiliations

  1. Biochemistry Department, Science College, King Saud University, Riyadh, Saudi Arabia

    Hanan Qasem

  2. Autism Research and Treatment Center, Riyadh, Saudi Arabia

    Laila Al-Ayadhi & Afaf El-Ansary

  3. Shaik AL-Amodi Autism Research Chair, King Saud University, Riyadh, Saudi Arabia

    Laila Al-Ayadhi & Afaf El-Ansary

  4. Physiology Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia

    Laila Al-Ayadhi

  5. Council for Nutritional and Environmental Medicine, Mo i Rana, Norway

    Geir Bjørklund

  6. Department of Neurological and Movement Sciences, University of Verona, Verona, Italy

    Salvatore Chirumbolo

  7. Central laboratory, Female Centre for Scientific and Medical Studies, King Saud University, Riyadh, Saudi Arabia

    Afaf El-Ansary

  8. Therapeutic Chemistry Department, National Research Center, Dokki, Guiza, Egypt

    Afaf El-Ansary

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  1. Hanan Qasem
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Qasem, H., Al-Ayadhi, L., Bjørklund, G. et al. Impaired lipid metabolism markers to assess the risk of neuroinflammation in autism spectrum disorder. Metab Brain Dis 33, 1141–1153 (2018). https://doi.org/10.1007/s11011-018-0206-6

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