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PHM142 Fall 2012 Coordinator: Dr. Jeffrey Henderson Instructor: Dr. David Hampson. Autism and Oxidative Stress. PHM142 Rachel Liu, Saejung Park, Yan Zhan Sarah Zhang. Overview. Autism Oxidative Stress How they connect Environmental and Genetic Factors Markers Testing Symptoms

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Autism and oxidative stress

PHM142 Fall 2012

Coordinator: Dr. Jeffrey Henderson

Instructor: Dr. David Hampson

Autism and Oxidative Stress

PHM142

Rachel Liu, Saejung Park, Yan Zhan Sarah Zhang


Overview
Overview

  • Autism

  • Oxidative Stress

  • How they connect

  • Environmental and Genetic Factors

  • Markers

  • Testing

  • Symptoms

  • Antioxidants and Autism

  • Summary


Autism
Autism

  • Diagnosed early childhood

    • Clinical symptoms do not usually show until 3 years of age

  • Loss in communication and socialization skills

  • Includes repetitive and unusual behaviours

  • Tied strongly to genetic factors


Oxidative stress
Oxidative Stress

  • Reactive Oxidative Species (ROS) needed for normal physiological functions

  • ROS = free radicals and non-radicals

    • Activated oxygen species

  • Increased production of ROS with decreased levels of antioxidants

  • Damaging to cellular tissue and organelles


Autism and oxidative stress1
Autism and Oxidative Stress

1. Autism

2. Physical changes

4. Increase in clinical symptoms

3. Increase Oxidative Stress


Autism and oxidative stress2
Autism and Oxidative Stress

1. Autism

2. Physical changes

4. Increase in clinical symptoms

3. Increase Oxidative Stress


Autism and oxidative stress3
Autism and Oxidative Stress

1. Autism

2. Physical changes

4. Increase in clinical symptoms

3. Increase Oxidative Stress


Autism and oxidative stress4
Autism and Oxidative Stress

1. Autism

2. Physical changes

4. Increase in clinical symptoms

3. Increase Oxidative Stress


Environmental and genetic factors
Environmental and Genetic Factors

  • Environmental

    • Toxins: mercury, lead, viruses, air pollutants

    • Heavy metals: disrupt sulfur metabolic pathways, reduce GSH

  • Genetic:

    • Glutathione-S-transferase M1 (GSTM1): decreased activity causes increase risk of oxidative stress

    • Paraoxonase 1 (PON1): detoxifies organophosphate


Markers of oxidative stress in autism
Markers of Oxidative Stress in Autism

  • Mitochondrial and immune dysfunction

  • Changed activities of antioxidant enzymes

    •  glutathione

    •  in ferritin and ceruloplasmin

    • Changed homocysteine/methio-nine metabolism

  •  3-nitrotyrosine

  •  products of lipid peroxidation

  •  in antioxidant selenium


Testing
Testing

  • Direct measurement of reactive oxidative species

    • Unstable and hard to measure

  • Measurement of antioxidant levels

    • Catalase, SOD, GSH assays etc.

  • Measurement of damaged molecules

    • Indirect but accurate

    • TBARS (thiobarbituic acid reactive substances assay)

      • Test for lipid peroxidation


Symptoms in autism due to oxidative stress
Symptoms in Autism due to Oxidative Stress

  • Mood and sleep disturbance

    • Immune activation and cytokines

  • Gastrointestinal disturbance

    • Increased levels of pro-inflammatory cytokines

  • Behavior abnormalities

    • Reduced GAD, increased glutamate levels


Antioxidants and autism
Antioxidants and Autism

  • Reduce oxidative stress and autistic symptoms

  • Vitamin B12, B6, C, E, Folate

  • NAC (n-acetylcysteine)

    • Maintain GSH level

    • Glutamate regulation


Summary
Summary

  • Testing

    • Direct measurement of reactive oxidative species

    • Measurement of damaged molecules

    • Measurement of antioxidant levels

  • Symptoms

    • Mood and sleep disturbance

    • Gastrointestinal disturbance

    • Behavior abnormalities

  • Antioxidants and Autism

    • Vitamin B12, B6, C, E, Folate

    • NAC (n-acetylcysteine)

    • Regulate GSH level and glutamate

1. Autism

2. Physical changes

  • Autism is a behavioral condition with distinct unusual behaviours such as loss in social skills. Oxidative stress is stress put on the body due to excessive production of oxidative reactive species.

  • The connection: Oxidative stress contributes by exacerbate autistic symptoms by affecting the levels of many biological substances

  • Environmental and genetic factors

    • Environmental: Heavy metals (ex mercury) : disrupt sulfur metabolic pathways, reduce GSH

    • Genetic: Glutathione-S-transferase M1 (GSTM1) and Paraoxonase 1 (PON1)

  • Markers

    • Includes products of lipid peroxidation

    •  homocysteine, 3-nitrotyrosine

    •  glutathione, ferritin and ceruloplasmin, methionine, antioxidant selenium

4. Increase in clinical symptoms

3. Increase Oxidative Stress


References
References

  • Sajdel-Sulkowska, Elizabeth M., Ming Xu, and Noriyuki Koibuchi. "Increase in Cerebellar Neurotrophin-3 and Oxidative Stress Markers in Autism." The Cerebellum 8.3 (2009): 366-72. Web. 19 Nov. 2012.

  • Chauhan, A., and V. Chauhan. "Oxidative Stress in Autism." Pathophysiology 13.3 (2006): 171-81. Web. 19 Nov. 2012.

  • Sajdel-Sulkowska, Elizabeth M., Boguslaw Lipinski, Herb Windom, TapanAudhya, and Woody McGinnis. "Oxidative Stress in Autism: Elevated Cerebellar 3-nitrotyrosine Levels." American Journal of Biochemistry and Biotechnology 4.2 (2008): 73-84. Web.19 Nov. 2012.

  • Volkmar, Fred R., and David Pauls. "Autism." The Lancet 362.9390 (2003): 1133-141. Web. 19 Nov. 2012.

  • Presier, Jean-Charles. "Oxidative Stress." Journal of Parenteral and Enteral Nutrition 36.2 (2012): 147-54. Web. 19 Nov. 2012.

  • Levy, Susan E., David S. Mandell, and Robert T. Schultz. "Autism." The Lancet 374.9701 (2009): 1627-638. Web. 19 Nov. 2012.

  • Kern, Janet, and Anne Jones. "Evidence of Toxicity, Oxidative Stress, and Neuronal Insult in Autism." Journal of Toxicology and Environmental Health Part B: Critical Reviews 9.6 (2006): 485-99. Web. 18 Nov. 2012.

  • Deth, Richard, Christina Muratore, Jorge Benzecry, Verna-Ann Power-Charnitsky, and MostafaWaly. "How Environmental and Genetic Factors Combine to Cause Autism: A Redox/methylation Hypothesis." NeuroToxicology 29.1 (2008): 190-201. Web. 18 Nov. 2012.

  • "#1181- Oxidative Stress in Autism: What Parents Should Know." ASA's 36th National Conference on Autism Spectrum Disorders (July 13-16, 2005). Autism Society of America, n.d. Web. 20 Nov. 2012. <https://asa.confex.com/asa/2005/techprogram/S1181.HTM>.

  • Choudhury, Paromita R. "Glutamate Mediated Signaling in the Pathophysiology of Autism Spectrum Disorders." Pharmacology, Biochemistry and Behavior 100.4 (2012): 841-49. Web. 20 Nov. 2012.

  • Bertoglio, Kiah, S. Jill James, Lesley Deprey, Norman Brule, and Robert L. Hendren. "Pilot Study of the Effect of Methyl B12 Treatment on Behavioral and Biomarker Measures in Children with Autism." The Journal of Alternative and Complementary Medicine 16.5 (2010): 555-60. Web. 20 Nov. 2012.

  • Geier, David A., Janet K. Kern, and Mark A. Geier. "A Prospective Study of Oxidative Stress Biomarkers in Autistic Disorders." Electronic Journal of Applied Psychology: Innovations in Autism 5.1 (2009): 2-10. Web. 21 Nov. 2012.


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