Dopamine

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Dopamine is a neurotransmitter with multiple roles in the body.

Dopamine synthesis[edit | edit source]

Dopamine is synthesized through the following pathway:

L-Phenylalanine → L-Tyrosine → L-DOPA → Dopamine

Dopamine, in turn, is a precursor to norepinephrine and epinephrine.[1]

Dopamine is incapable of crossing the blood-brain barrier, so it must be produced in neurons for brain activity or in the adrenal glands and the gut for peripheral activity.

Iron is important in the expression of dopamine receptors in the brain[2] and is also a cofactor in for tyrosine hydroxylase, the enzyme that catalyzes the conversion of tyrosine to L-DOPA.

Nervous system[edit | edit source]

Dopamine plays a role in executive function, motor control, motivation, arousal.

The largest sources of dopamine in the brain are in the substantia nigra (SN) and ventral tegmental area (VTA). The SN and VTA are both components of the basal ganglia. Dopamine neurons spread to the rest of the brain via two* main pathways:[1]

  • Nigrostriatal pathway: connects SN to the striatum
  • Mesocorticolimbic pathway: connects VTA to the striatum, limbic areas, and prefrontal cortex

Some dopamine is also synthesized in the hypothalamus. It takes a third, separate pathway to the pituitary gland, where it inhibits the release of prolactin (a hormone that helps regulate the immune system).

Immune system[edit | edit source]

Dopamine reduces systemic inflammation by blocking inflammasome activation.[3][4]

Dopamine has a role in the activity of lymphocytes. It activates native t cells but inhibits the activity of activated t cells.[5] However, dopamine may also induce the release of interleukin-17 in rheumatoid arthritis.[6]

Inflammation may also have a role in dopamine production. A study of Hepatitis C patients found looked at how interferon alpha treatment (which increases immune system activity) affected dopamine precursors. They found decreased levels of tetrahydrobiopterin (BH4), which is a cofactor in the conversion of L-Phenylalanine to L-Tyrosine and L-Tyrosine to L-DOPA. At the same time, levels of BH2 (tetrahydrobipterin's inactive form) were much higher than normal. The researchers also found reduced conversion of phenylalanine to tyrosine in the cerebrospinal fluid, which are associated with decreased dopamine in the brain.[7]

Fatigue[edit | edit source]

Dopamine Imbalance Hypothesis[edit | edit source]

The dopamine imbalance hypothesis suggests pathological fatigue occurs due to a dopamine imbalance in the central nervous system.[8] More specifically, dopamine may not travel effectively through the mesocorticolimbic pathway, disrupting communication in the brain.

Support for this hypothesis is based on prior research findings regarding fatigue in conditions like multiple sclerosis (MS), traumatic brain injury (TBI), and chronic fatigue syndrome. To summarize, research has linked fatigue to physical damage and low connectivity in regions of the brain with lots of dopamine neurons. Medications that increase dopamine levels have been shown to improve reported fatigue in chronic fatigue syndrome, TBI, and cancer.[8]

Chronic fatigue syndrome[edit | edit source]

Studies have found lower levels of the dopamine precursor tyrosine[9] and reduced activation in the basal ganglia[10][11], the region of the brain with the highest concentration of dopaminergic neurons.

Fibromyalgia[edit | edit source]

Small, preliminary studies have found evidence of abnormal dopamine metabolism in the brains of fibromyalgia patients.[12][13][14][15]

Other conditions[edit | edit source]

Parkinson's disease involves the loss of dopaminergic neurons in the midbrain and subsequently reduced dopamine. Schizophrenia, ADHD and restless leg syndrome are also associated with altered dopamine.

Cerebralspinal iron is decreased in restless legs syndrome despite normal serum levels.[16]

In addition to its neurological effects, reduced dopamine may also have immunological effects in these diseases.

Altered dopamine metabolism may play a role in a number of autoimmune diseases.[17]

Dopaminergic neurons are thought to play a role in epileptic seizures arising from the limbic system.[18]

Altering dopamine levels[edit | edit source]

Mice fed a ketogenic diet had increased activity of dopaminergic neurons.[19]

See also[edit | edit source]

Learn more[edit | edit source]

References[edit | edit source]

  1. ↑ 1.0 1.1 Dobryakova, Ekaterina; Genova, Helen M.; DeLuca, John; Wylie, Glenn R. (March 12, 2015). "The Dopamine Imbalance Hypothesis of Fatigue in Multiple Sclerosis and Other Neurological Disorders". Frontiers in Neurology. 6. doi:10.3389/fneur.2015.00052. ISSN 1664-2295.
  2. ↑ Mb, Youdim; D, Ben-Shachar; R, Ashkenazi; S, Yehuda (1983). "Brain Iron and Dopamine Receptor Function". Advances in biochemical psychopharmacology. PMID 6138953. Retrieved May 28, 2020.
  3. ↑ Yan, Yiqing; Jiang, Wei; Liu, Lei; Wang, Xiaqiong; Ding, Chen; Tian, Zhigang; Zhou, Rongbin (January 2015). "Dopamine Controls Systemic Inflammation through Inhibition of NLRP3 Inflammasome". Cell. 160 (1–2): 62–73. doi:10.1016/j.cell.2014.11.047. ISSN 0092-8674.
  4. ↑ Bordon, Yvonne (February 2015). "Dopamine blocks inflammasome activation". Nature Reviews Immunology. 15 (2): 69–69. doi:10.1038/nri3817. ISSN 1474-1741.
  5. ↑ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856781/
  6. ↑ http://www.nature.com/nrd/journal/v10/n4/full/nrd3422.html
  7. ↑ Felger, JC; Li, L; Marvar, PJ; Woolwine, BJ; Harrison, DG; Raison, CL; Miller, AH (July 2013). "Tyrosine Metabolism During Interferon-Alpha Administration: Association With Fatigue and CSF Dopamine Concentrations". Brain, behavior, and immunity. PMID 23072726. Retrieved May 28, 2020.
  8. ↑ 8.0 8.1 Dobryakova, Ekaterina; Genova, Helen M.; DeLuca, John; Wylie, Glenn R. (2015). "The Dopamine Imbalance Hypothesis of Fatigue in Multiple Sclerosis and Other Neurological Disorders". Frontiers in Neurology. 6. doi:10.3389/fneur.2015.00052. ISSN 1664-2295. PMC 4357260. PMID 25814977.
  9. ↑ Georgiades, Evelina; Behan, Wilhelmina M.H.; Kilduff, Liam P.; Hadjicharalambous, Marios; Mackie, Eileen E.; Wilson, John; Ward, Susan A.; Pitsiladis, Yannis P. (August 1, 2003). "Chronic fatigue syndrome: new evidence for a central fatigue disorder". Clinical Science. 105 (2): 213–218. doi:10.1042/CS20020354. ISSN 0143-5221.
  10. ↑ http://www.fasebj.org/cgi/content/meeting_abstract/26/1_MeetingAbstracts/1035.20
  11. ↑ Miller, Andrew H.; Jones, James F.; Drake, Daniel F.; Tian, Hao; Unger, Elizabeth R.; Pagnoni, Giuseppe (May 23, 2014). "Decreased Basal Ganglia Activation in Subjects with Chronic Fatigue Syndrome: Association with Symptoms of Fatigue". PLOS ONE. 9 (5): e98156. doi:10.1371/journal.pone.0098156. ISSN 1932-6203. PMC 4032274. PMID 24858857.
  12. ↑ Wood, PB; Glabus, MF; R, Simpson; Jc, Patterson (June 2009). "Changes in Gray Matter Density in Fibromyalgia: Correlation With Dopamine Metabolism". The journal of pain : official journal of the American Pain Society. PMID 19398377. Retrieved May 28, 2020.
  13. ↑ Wood, PB; Patterson, JC; Jj, Sunderland; Kh, Tainter; Mf, Glabus; Dl, Lilien (January 2007). "Reduced Presynaptic Dopamine Activity in Fibromyalgia Syndrome Demonstrated With Positron Emission Tomography: A Pilot Study". The journal of pain : official journal of the American Pain Society. PMID 17023218. Retrieved May 28, 2020.
  14. ↑ http://www.ncbi.nlm.nih.gov/pubmed/17610577
  15. ↑ http://www.ncbi.nlm.nih.gov/pubmed/24449585
  16. ↑ Ciattei, Jennifer. "Causes of Restless Legs Syndrome (RLS) | The Johns Hopkins Center for Restless Legs Syndrome". hopkinsmedicine.org. Retrieved May 28, 2020.
  17. ↑ Pacheco, Rodrigo; Contreras, Francisco; Zouali, Moncef (2014). "The Dopaminergic System in Autoimmune Diseases". Frontiers in Immunology. 5. doi:10.3389/fimmu.2014.00117. ISSN 1664-3224.
  18. ↑ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774988/
  19. ↑ http://www.ncbi.nlm.nih.gov/pubmed/24769322

A substance that acts with another substance to bring about certain effects.[1] In biochemistry, a cofactor is a molecule that is necessary for a given biochemical reaction, but is not an enzyme or substrate of the reaction.

cofactor A substance that acts with another substance to bring about certain effects. In biochemistry, a cofactor is a molecule that is necessary for a given biochemical reaction, but is not an enzyme or substrate of the reaction.

enzyme a substance produced by a living organism which acts as a catalyst to bring about a specific biochemical reaction.

central nervous system (CNS) - One of the two parts of the human nervous system, the other part being the peripheral nervous system. The central nervous system consists of the brain and spinal cord, while the peripheral nervous system consists of nerves that travel from the central nervous system into the various organs and tissues of the body.

The clear yellowish fluid that remains from blood plasma after clotting factors have been removed by clot formation. (Blood plasma is simply blood that has had its blood cells removed.)[2]

serum The clear yellowish fluid that remains from blood plasma after clotting factors have been removed by clot formation. (Blood plasma is simply blood that has had its blood cells removed.)

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