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Is caffeine toxic to our nervous system?

How does caffeine affect your brain ?

The researcher (Vulin et al., 2022) used novel biomarkers of neural function in neuroblastoma SH-SY5Y cells and markers of general toxicity in human hepatoma HepG2 cells (Donato, Tolosa, & Gómez-Lechón, 2015) to assess the neurotoxicity of environmentally relevant concentrations of caffeine.

What are biomarkers?

Biomarkers are quantitative measurements that offer insight into preclinical and clinical data by providing details about biological processes, a disease state, or the response to treatment (Institute of Medicine Forum on Neuroscience and Nervous System Disorders, 2008).

Experimental analysis

Numerous experiments were conducted to examine the impact of caffeine on the two types of cells. The absence of cytotoxicity and effects on mitochondrial membrane potential demonstrated the low toxicity of caffeine.

Only at very high concentrations did caffeine’s ability to decrease cell viability in SH-SY5Y cells become apparent (Sangaunchom & Dharmasaroja, 2020). Furthermore, caffeine also has a limited ability to cause oxidative stress and genotoxicity (Santos-Silva, Montagner, & Martinez, 2018).

Because it alters some of the essential components of neurotransmitter pathways, caffeine can disrupt synaptic transmission in neurons. Because of the disturbance of MAO enzyme activity and the expression of HTR3A, DRD2, and MAOB, the serotonin and dopamine pathways appear to be the most susceptible to caffeine.

Figure 1: Caffeine’s effects (10 ng/L, 10 μg/L, and 10 mg/L) on the expression of specific genes in SH-SY5Y cells after a 24-hour treatment. RQ-PCR analysis was used to determine gene expression. A Clustered Image Map (CIM) displaying overexpressed (green) and underexpressed (red) genes was created using the mean values of gene expression relative to control (equals 1) from three separate experiments (Vulin et al., 2022).

All things considered, more research should be done on the neurotoxic effects of caffeine at environmentally relevant concentrations. Caffeine may have more molecular targets than is currently believed. This was demonstrated through the use of novel neuronal function biomarkers that were connected to important components of neurotransmitter pathways and molecules involved in neurotransmitter exocytosis. The study’s overall findings indicate that it would be better to treat the growing concern about caffeine’s presence in the environment seriously than to ignore it.

References

Donato, M. T., Tolosa, L., & Gómez-Lechón, M. J. (2015). Culture and functional characterization of human hepatoma HepG2 cells. Methods in Molecular Biology, 1250, 77-93. https://doi.org/10.1007/978-1-4939-2074-7_5. PMID: 26272135.

Institute of Medicine (US) Forum on Neuroscience and Nervous System Disorders. (2008). Neuroscience Biomarkers and Biosignatures: Converging Technologies, Emerging Partnerships, Workshop Summary. National Academies Press (US). https://www.ncbi.nlm.nih.gov/books/NBK53103/

Sangaunchom, P., & Dharmasaroja, P. (2020). Caffeine potentiates ethanol-induced neurotoxicity through mTOR/p70S6K/4E-BP1 inhibition in SH-SY5Y cells. International Journal of Toxicology, 39(2), 131-140. https://doi.org/10.1177/1091581819900150. PMID: 31955628.

Santos-Silva, T. G., Montagner, C. C., & Martinez, C. B. R. (2018). Evaluation of caffeine effects on biochemical and genotoxic biomarkers in the neotropical freshwater teleost Prochilodus lineatus. Environmental Toxicology and Pharmacology, 58, 237-242. https://doi.org/10.1016/j.etap.2018.02.002. PMID: 29438913.

Vichai, V., & Kirtikara, K. (2006). Sulforhodamine B colorimetric assay for cytotoxicity screening. Nature Protocols, 1, 1112–1116. https://doi.org/10.1038/nprot.2006.179 Vulin, I., Tenji, D., Teodorovic, I., Kaisarevic, S. (2022). Assessment of caffeine neurotoxicity using novel biomarkers of neural function in SH-SY5Y cells – Is there a need for environmental concern? Chemico-Biological Interactions, 365, Article 110082. https://doi.org/10.1016/j.cbi.2022.110082.

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