Glucose transporter 1 deficiency, AMP-activated protein kinase activation and immune dysregulation in autism spectrum disorder: Novel biomarker sources for clinical diagnosis
The neurophysiological basis of autism spectrum disorder (ASD) is still uncertain. Nevertheless, studies support the hypotheses that oxidative stress, neuroinflammation, immune dysregulation, and metabolic stress are contributors. In this study, the serum levels of 3-nitrotyrosine (3-NT), hypoxia-in...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Saudi Journal of Biological Sciences |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1319562X23002942 |
| _version_ | 1797385250001649664 |
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| author | Widad M. Al-Bishri |
| author_facet | Widad M. Al-Bishri |
| author_sort | Widad M. Al-Bishri |
| collection | DOAJ |
| description | The neurophysiological basis of autism spectrum disorder (ASD) is still uncertain. Nevertheless, studies support the hypotheses that oxidative stress, neuroinflammation, immune dysregulation, and metabolic stress are contributors. In this study, the serum levels of 3-nitrotyrosine (3-NT), hypoxia-inducible factor 1 α (HIF-1 α), heat shock protein 70 (HSP-70), interleukin-17A (IL-17A), IL-35, vitamin D3 (VITD), glucose transporter-1 (GUT1), and AMP-activated protein kinase (AMPK) were estimated in Saudi ASD children versus age-matched neurotypical controls, aiming to investigate whether these parameters have potential roles in the pathophysiologic mechanisms of ASD and hoping to find a reliable marker for early ASD diagnosis. This study included 25 ASD children and 25 typically developing children (3–11 years old). The diagnosis of ASD cases was made based on the Autism Diagnostic Observation Schedule (ADOS) and the Statistical Manual of Mental Disorders (DSM-5). ASD subjects were commonly male and revealed an intelligence quotient (IQ) < 70.The results detected that ASD children have remarkable greater serum levels of nitrosative stress (3-NT), hypoxia (HIF-1 α), inflammatory (HSP-70, IL-17A, and AMPK) biomarkers and lower serum levels of anti-inflammatory (IL-35 and VITD) and metabolic stress (GUT-1) biomarkers versus age-matched controls (P ≤ 0.0001). Pearson's correlation study revealed that 3-NT was positively associated with HIF-1 α and HSP-70. HIF-1 α was also positively correlated with HSP-70. AMPK was positively associated with GUT-1, however, IL-17A was negatively correlated with IL-35 and VITD.Limitation:No specific therapeuticdrugs were administered in this study, and further studies are required to confirm the role of the selected biomarkers in ASD managements. Conclusion: Changes in concentrations of different biomarkers indicate that they are involved in oxidative stress, metabolic stress, immune dysregulation and ASD pathogenesis. Hence, these parameters can prove to be promising biomarkers as well as therapeutic targets for the timely diagnosis and treatment of ASD patients. |
| first_indexed | 2024-03-08T21:51:32Z |
| format | Article |
| id | doaj.art-e44a14b111474f919dd3b02fa65ea145 |
| institution | Directory Open Access Journal |
| issn | 1319-562X |
| language | English |
| last_indexed | 2024-03-08T21:51:32Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Saudi Journal of Biological Sciences |
| spelling | doaj.art-e44a14b111474f919dd3b02fa65ea1452023-12-20T07:33:41ZengElsevierSaudi Journal of Biological Sciences1319-562X2023-12-013012103849Glucose transporter 1 deficiency, AMP-activated protein kinase activation and immune dysregulation in autism spectrum disorder: Novel biomarker sources for clinical diagnosisWidad M. Al-Bishri0Department of Biochemistry, College of Science, University of Jeddah, Jeddah 80327, Saudi ArabiaThe neurophysiological basis of autism spectrum disorder (ASD) is still uncertain. Nevertheless, studies support the hypotheses that oxidative stress, neuroinflammation, immune dysregulation, and metabolic stress are contributors. In this study, the serum levels of 3-nitrotyrosine (3-NT), hypoxia-inducible factor 1 α (HIF-1 α), heat shock protein 70 (HSP-70), interleukin-17A (IL-17A), IL-35, vitamin D3 (VITD), glucose transporter-1 (GUT1), and AMP-activated protein kinase (AMPK) were estimated in Saudi ASD children versus age-matched neurotypical controls, aiming to investigate whether these parameters have potential roles in the pathophysiologic mechanisms of ASD and hoping to find a reliable marker for early ASD diagnosis. This study included 25 ASD children and 25 typically developing children (3–11 years old). The diagnosis of ASD cases was made based on the Autism Diagnostic Observation Schedule (ADOS) and the Statistical Manual of Mental Disorders (DSM-5). ASD subjects were commonly male and revealed an intelligence quotient (IQ) < 70.The results detected that ASD children have remarkable greater serum levels of nitrosative stress (3-NT), hypoxia (HIF-1 α), inflammatory (HSP-70, IL-17A, and AMPK) biomarkers and lower serum levels of anti-inflammatory (IL-35 and VITD) and metabolic stress (GUT-1) biomarkers versus age-matched controls (P ≤ 0.0001). Pearson's correlation study revealed that 3-NT was positively associated with HIF-1 α and HSP-70. HIF-1 α was also positively correlated with HSP-70. AMPK was positively associated with GUT-1, however, IL-17A was negatively correlated with IL-35 and VITD.Limitation:No specific therapeuticdrugs were administered in this study, and further studies are required to confirm the role of the selected biomarkers in ASD managements. Conclusion: Changes in concentrations of different biomarkers indicate that they are involved in oxidative stress, metabolic stress, immune dysregulation and ASD pathogenesis. Hence, these parameters can prove to be promising biomarkers as well as therapeutic targets for the timely diagnosis and treatment of ASD patients.http://www.sciencedirect.com/science/article/pii/S1319562X23002942AutismNeuroinflammationHeat shock protein- 70Glucose transporter −1AMP-activated protein kinase |
| spellingShingle | Widad M. Al-Bishri Glucose transporter 1 deficiency, AMP-activated protein kinase activation and immune dysregulation in autism spectrum disorder: Novel biomarker sources for clinical diagnosis Saudi Journal of Biological Sciences Autism Neuroinflammation Heat shock protein- 70 Glucose transporter −1 AMP-activated protein kinase |
| title | Glucose transporter 1 deficiency, AMP-activated protein kinase activation and immune dysregulation in autism spectrum disorder: Novel biomarker sources for clinical diagnosis |
| title_full | Glucose transporter 1 deficiency, AMP-activated protein kinase activation and immune dysregulation in autism spectrum disorder: Novel biomarker sources for clinical diagnosis |
| title_fullStr | Glucose transporter 1 deficiency, AMP-activated protein kinase activation and immune dysregulation in autism spectrum disorder: Novel biomarker sources for clinical diagnosis |
| title_full_unstemmed | Glucose transporter 1 deficiency, AMP-activated protein kinase activation and immune dysregulation in autism spectrum disorder: Novel biomarker sources for clinical diagnosis |
| title_short | Glucose transporter 1 deficiency, AMP-activated protein kinase activation and immune dysregulation in autism spectrum disorder: Novel biomarker sources for clinical diagnosis |
| title_sort | glucose transporter 1 deficiency amp activated protein kinase activation and immune dysregulation in autism spectrum disorder novel biomarker sources for clinical diagnosis |
| topic | Autism Neuroinflammation Heat shock protein- 70 Glucose transporter −1 AMP-activated protein kinase |
| url | http://www.sciencedirect.com/science/article/pii/S1319562X23002942 |
| work_keys_str_mv | AT widadmalbishri glucosetransporter1deficiencyampactivatedproteinkinaseactivationandimmunedysregulationinautismspectrumdisordernovelbiomarkersourcesforclinicaldiagnosis |