The title of this post likely left you confused, you're probably wondering first of all, how can a worm be on the spectrum and second of all why does it matter? I was wondering these same things in my first meeting with Dr. Streifel when she was explaining her potential research projects I could be a part of. Through my research experience, I learned how much the microscopic worms known as C. elegans can inform us about the human brain's dopamine pathways and how a trace metal in our water may be triggering inattentive ADHD.
Dr. Sydney Brenner proposed C. elegans as an ideal model to learn about a myriad of different human diseases. These hermaphroditic worms that live for less than 3 weeks mirror over "40% of human disease related genes" (Airton et al., 2022). Despite the fact that C. elegans have a mere 302 neurons as compared to the 86 billion neurons present in the human brain, C. elegans have a fully intact dopaminergic system and are fully capable of having ADHD. Despite a few key differences, the worms have most of the same receptors, synaptic components, and neurotransmitters. (Schmeisser and Parker, 2018). A tell tale sign of ADHD is low level dopamine, with a major culprit being dysregulation of the dopamine transporter (DAT). The dopamine transporter is an essential target for medication and a hot topic of research (Madras, 2005). In my research we can visualize the dopamine transporters using worms with a green fluorescence protein.
Now that you are convinced that a 1nm nematode can have ADHD and is also an excellent animal model for experimentation, you are ready to hear the premise of my research. Trace metals such as manganese, iron, calcium, copper, and cobalt are essential for the function of our body, but too much and there can be deadly neurotoxic effects on your brain. The metal we are studying, manganese, can cause a deadly disease known as Manganism which results in Parkinson like symptoms. It has also been known to cause ADHD like symptoms in children exposed to high levels of the metal (Farias, 2010). In 2020 there was an epidemiological study conducted on children across Denmark that found that manganese levels greater than 100ug/L caused a 51% increase in the inattentive subtype of ADHD in females, and a 20% increase in males (Shullehner, 2019). With the "safe" limit of manganese in US drinking water being 300 ug/L, I am eager to determine if low level exposure to manganese causes an increase in the incidence of ADHD in my C. elegans ("Manganese in Drinking Water," 2023).
References
Farias, A. (2010). Manganese in children with attention-deficit/hyperactivity disorder: Relationship with methylphenidate exposure. Journal of child and adolescent psychopharmacology. https://pubmed.ncbi.nlm.nih.gov/20415606/#:~:text=Earlier%20studies%20associated%20elevated%20levels,by%20high%20levels%20of%20Mn.
Madras, B. (2005). The dopamine transporter and attention-deficit/hyperactivity disorder. Biological psychiatry. https://pubmed.ncbi.nlm.nih.gov/15950014
Manganese in drinking water fact sheet & frequently asked questions. Iowa National Department of Resources. (2023). https://www.iowadnr.gov/Portals/idnr/uploads/water/wso/docs/ManganeseFactSheetandFAQ.pdf
Martins, A. C., Gubert, P., Li, J., Ke, T., Nicolai, M. M., Moura, A. V., Bornhorst, J., Bowman, A. B., & Aschner, M. (2022, September 29). caenorhabditis elegans as a model to study manganese-induced neurotoxicity. Biomolecules. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9599542/#B23-biomolecules-12-01396
Schmeisser, K., & Parker, A. J. (2018). Worms on the Spectrum - C. elegans models in autism research. Experimental Neurology, 299, 199–206. https://doi.org/10.1016/j.expneurol.2017.04.007
Schullehner, J., Thygesen, M., Kristiansen, S. M., Hansen, B., Pedersen, C. B., & Dalsgaard, S. (2019). Exposure to manganese in drinking water during childhood and association with attention-deficit hyperactivity disorder: A nationwide cohort study. SSRN Electronic Journal. https://doi.org/10.2139/ssrn.3369767
Your post on is very interesting. The concept of using C. elegans as a model for studying ADHD and the parallels between their dopaminergic system and our own are truly intriguing. It reminds me of recent research on the gut-brain connection and its potential relevance to your work. Studies have shown how the gut microbiome can influence neurotransmitters like dopamine, which play a crucial role in ADHD. Your research could potentially shed light on this fascinating intersection of neurobiology and gut health, offering a more comprehensive understanding of the condition. I'm excited to see where your research leads and how it might contribute to this broader scientific conversation.
ReplyDeleteHow does manganese cause ADHD? Could it possibly affect processes in humans that are not present in C. elegans? That would mean that the c. elegans might not have a response to it. Love your research!
ReplyDelete@lianaR436 Interestingly enough, Dr. Streifel is working on a study on just that! Your gut has an enormous amount of your body's neurons so she is looking at the interaction between manganese and the neurons in the gut in mice. She is looking at how astrocytes (an important neuron support cell) and neurons react to acute manganese exposure. She is analyzing the data now!
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