Testing a Choline Diet in Neuroligin-Deficient C. elegans to Reduce Repetitive Behavior in Autism

Authors

  • Sasha Balasingam Los Gatos High School
  • Cathy Messenger Los Gatos High School

DOI:

https://doi.org/10.47611/jsrhs.v11i3.2846

Keywords:

Keywords: Autism Spectrum Disorder, C. elegans, neuroligin, repetitive behavior, acetylcholine, choline

Abstract

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by  obsessive adherence to repetitive motion and behavior. Previously my research tested whether neuroligin, a brain molecule and potential determinant of behavioral traits in autism, could be used in neuroligin-deficient C.elegans (strain NLG-1) to model autism. The experiment studied the sensitivity of neuroligin-deficient C. elegan to sensory stimuli, a core symptom of autism, and the results led to the conclusion that NLG-1 C. elegans could be used as a potential model for autism in worms. This project is a continuation study from last year that tested whether choline supplementation reduced repetitive locomotion in neuroligin-deficient C. elegans. Since people with neurological disorders are often deficient in the neurotransmitter acetylcholine, it was hypothesized that increasing the amount of choline, a building block of acetylcholine, would reduce repetitive behaviors. The C. elegans were age-synched to test three different age groups of worms, and over a 1-minute period, and the repetitive movement of the worms exposed to choline was compared to worms without choline using microscope camera software. The results showed the addition of choline in the diet significantly reduced the amount of repetitive locomotion in NLG-1 C. elegans in all 3 age groups. This study suggests that for people with ASD, adding choline to the diet in their daily schedule may help them reduce repetitive behavior. On a larger scale, scientists can use NLG-1 C. elegans to target neurochemical systems to develop early treatments, and ultimately reduce the significant deficits of autism.

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Author Biography

Cathy Messenger, Los Gatos High School

Los Gatos High School Science Department Chair and AP Research Advisor

 

References or Bibliography

Agam, G., Taylor, Z., Vainer, E., & Golan, H. M. (2020). The influence of choline treatment on behavioral and neurochemical autistic-like phenotype in mthfr-deficient mice. Translational Psychiatry, 10(1). https://doi.org/10.1038/s41398-020-01002-1

Ahmed, N. Y., Knowles, R., & Dehorter, N. (2019). New insights into cholinergic neuron diversity. Frontiers in Molecular Neuroscience, 12. https://doi.org/10.3389/fnmol.2019.00204

American Psychiatric Association . Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: 2000.

Amodeo, D. A., Yi, J., Sweeney, J. A., & Ragozzino, M. E. (2014). Oxotremorine treatment reduces repetitive behaviors in BTBR t+ tf/J mice. Frontiers in Synaptic Neuroscience, 6. https://doi.org/10.3389/fnsyn.2014.00017

Autism and Vaccines | Vaccine Safety | CDC. (2021, December 1). Centers for Disease Control and Prevention. Retrieved March 9, 2022, from https://www.cdc.gov/vaccinesafety/concerns/autism.html

Bang, M., Lee, S. H., Cho, S.-H., Yu, S.-A., Kim, K., Lu, H. Y., Chang, G. T., & Min, S. Y. (2017). Herbal medicine treatment for children with autism spectrum disorder: A systematic review. Evidence-Based Complementary and Alternative Medicine, 2017, 1-12. https://doi.org/10.1155/2017/8614680

Bellier, J.-P., & Kimura, H. (2007). Acetylcholine synthesis by choline acetyltransferase of a peripheral type as demonstrated in adult rat dorsal root ganglion. Journal of Neurochemistry, 101(6), 1607-1618. https://doi.org/10.1111/j.1471-4159.2007.04458.x

Bishop, S. L., Richler, J., Cain, A. C., & Lord, C. (2007). Predictors of perceived negative impact in mothers of children with autism spectrum disorder. American Journal on Mental Retardation, 112(6), 450. https://doi.org/10.1352/0895-8017(2007)112[450:POPNII]2.0.CO;2

Butterweck, V., Winterhoff, H., & Herkenham, M. (2001). St John's wort, hypericin, and imipramine: A comparative analysis of mRNA levels in brain areas involved in HPA axis control following short-term and long-term administration in normal and stressed rats. Molecular Psychiatry, 6(5), 547-564. https://doi.org/10.1038/sj.mp.4000937

Damiano, C. R., Mazefsky, C. A., White, S. W., & Dichter, G. S. (2014). Future directions for research in autism spectrum disorders. Journal of Clinical Child & Adolescent Psychology, 43(5), 828-843. https://doi.org/10.1080%2F15374416.2014.945214

Dawson, G., Rogers, S., Munson, J., Smith, M., Winter, J., Greenson, J., Donaldson, A., & Varley, J. (2010). Randomized, controlled trial of an intervention for toddlers with autism: The early start Denver model. Pediatrics, 125(1), e17-e23. https://doi.org/10.1542/peds.2009-0958

Faras, H., Al ateeqi, N., & Tidmarsh, L. (2010). autism spectrum disorders. Annals of Saudi Medicine, 30(4), 295-300. https://doi.org/10.4103/0256-4947.65261

Hunter, P. (2008). The paradox of model organisms. EMBO Reports, 9(8), 717-720. https://doi.org/10.1038%2Fembor.2008.142

Karvat, G., & Kimchi, T. (2013). Acetylcholine elevation relieves cognitive rigidity and social deficiency in a mouse model of autism. Neuropsychopharmacology, 39(4), 831-840. https://doi.org/10.1038/npp.2013.274

Katz, M., Corson, F., Keil, W., Singhal, A., Bae, A., Lu, Y., Liang, Y., & Shaham, S. (2019). Glutamate spillover in C. elegans triggers repetitive behavior through presynaptic activation of mgl-2/mglur5. Nature Communications, 10(1). https://doi.org/10.1038/s41467-019-09581-4

King, B. H., Hollander, E., Sikich, L., Mccracken, J. T., Scahill, L., Bregman, J. D., Donnelly, C. L., Anagnostou, E., Dukes, K., Sullivan, L., Hirtz, D., Wagner, A., & Ritz, L. (2009). Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior. Archives of General Psychiatry, 66(6), 583. https://doi.org/10.1001/archgenpsychiatry.2009.30

Lam, K. S.l., Aman, M. G., & Arnold, L. E. (2006). Neurochemical correlates of autistic disorder: A review of the literature. Research in Developmental Disabilities, 27(3), 254-289. https://doi.org/10.1016/j.ridd.2005.03.003

Levy, S. E., & Hyman, S. L. (2008). Complementary and alternative medicine treatments for children with autism spectrum disorders. Child and Adolescent Psychiatric Clinics of North America, 17(4), 803-820. https://doi.org/10.1016/j.chc.2008.06.004

Lynch, R., Diggins, E. L., Connors, S. L., Zimmerman, A. W., Singh, K., Liu, H., Talalay, P., & Fahey, J. W. (2017). Sulforaphane from broccoli reduces symptoms of autism: A follow-up case series from a randomized double-blind study. Global Advances in Health and Medicine, 6, 2164957X1773582. https://doi.org/10.1177/2164957X17735826

Matthies, D. S., Fleming, P. A., Wilkes, D. M., & Blakely, R. D. (2006). The caenorhabditis elegans choline transporter cho-1 sustains acetylcholine synthesis and motor function in an activity-dependent manner. Journal of Neuroscience, 26(23), 6200-6212. https://doi.org/10.1523/JNEUROSCI.5036-05.2006

Mcdermott, C. R., Farmer, C., Gotham, K. O., & Bal, V. H. (2020). Measurement of subcategories of repetitive behaviors in autistic adolescents and adults. autism in Adulthood, 2(1), 48-60. https://doi.org/10.1089/aut.2019.0056

Nadeau, J., Sulkowski, M. L., Ung, D., Wood, J. J., Lewin, A. B., Murphy, T. K., May, J. E., & Storch, E. A. (2011). Treatment of comorbid anxiety and autism spectrum disorders. Neuropsychiatry, 1(6), 567-578. https://doi.org/10.2217/npy.11.62

Neuroligin dependence of social behavior in Caenorhabditis elegans provides a model to investigate an autism-associated gene. (n.d.). https://doi.org/10.1093/hmg/ddaa232

Orenbuch, A., Fortis, K., Taesuwan, S., Yaffe, R., Caudill, M. A., & Golan, H. M. (2019). Prenatal nutritional intervention reduces autistic-like behavior rates among mthfr-deficient mice. Frontiers in Neuroscience, 13. https://doi.org/10.3389/fnins.2019.00383

Picciotto, M., Higley, M., & Mineur, Y. (2012). Acetylcholine as a neuromodulator: Cholinergic signaling shapes nervous system function and behavior. Neuron, 76(1), 116-129. https://doi.org/10.1016/j.neuron.2012.08.036

Rawsthorne, H., Calahorro, F., Feist, E., Holden-dye, L., O'connor, V., & Dillon, J. (2020). Neuroligin dependence of social behavior in caenorhabditis elegans provides a model to investigate an autism-associated gene. Human Molecular Genetics, 29(21), 3546-3553. https://doi.org/10.1093/hmg/ddaa232

Rojas, D. C. (2014). The role of glutamate and its receptors in autism and the use of glutamate receptor antagonists in treatment. Journal of Neural Transmission, 121(8), 891-905. https://doi.org/10.1007/s00702-014-1216-0

Soorya, L., Kiarashi, J., & Hollander, E. (2008). Psychopharmacologic interventions for repetitive behaviors in autism spectrum disorders. Child and Adolescent Psychiatric Clinics of North America, 17(4), 753-771. https://doi.org/10.1016/j.chc.2008.06.003

Stigler, K. A., & Mcdougle, C. J. (2008). Pharmacotherapy of irritability in pervasive developmental disorders. Child and Adolescent Psychiatric Clinics of North America, 17(4), 739-752. https://doi.org/10.1016/j.chc.2008.06.002

Tata, A., Velluto, L., D'angelo, C., & Reale, M. (2014). Cholinergic system dysfunction and neurodegenerative diseases: Cause or effect? CNS & Neurological Disorders - Drug Targets, 13(7), 1294-1303. https://doi.org/10.2174/1871527313666140917121132

Volkmar, F. R., & Wolf, J. M. (2013). When children with autism become adults. World Psychiatry, 12(1), 79-80. https://doi.org/10.1002/wps.20020

Published

08-31-2022

How to Cite

Balasingam, S., & Messenger, C. (2022). Testing a Choline Diet in Neuroligin-Deficient C. elegans to Reduce Repetitive Behavior in Autism. Journal of Student Research, 11(3). https://doi.org/10.47611/jsrhs.v11i3.2846

Issue

Section

AP Capstone™ Research