Dopamine

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Dopamine is a neurotransmitter with multiple roles in the body.

Dopamine synthesis[edit | edit source]

Dopamine is synthesized in neurons and the adrenal glands.

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

Dopamine is incapable of crossing the blood-brain barrier so it must be produced in the brain for neuronal activity, or peripherally for peripheral activity.

Peripheral dopamine is produced by the adrenal glands and the gut.

BH4 is a cofactor in the conversion of L-Phenylalanine to L-Tyrosine and L-Tyrosine to L-DOPA. The availability of BH4 is dependent on the methylation cycle.

Dopamine is a precursor to norepinephrine and epinephrine.

Iron is important in the expression of dopamine receptors in the brain[1] 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 source of dopamine in the brain is in the substantia nigra and ventral segmental area, both components of the basal ganglia.

Immune system[edit | edit source]

Dopamine reduces systemic inflammation by blocking inflammasome activation.[2][3]

Dopamine has a role in the activity of lymphocytes. It activates native t cells but inhibits the activity of activated t cells.[4] However, dopamine may also induce the release of interleukin-17 in rheumatoid arthritis.[5]

Inflammation may also have a role in dopamine production. A study of Hepatitis C patients found that interferon alpha treatment resulted in significantly increased levels of dihydrobiopterin (BH2) and decreased tetrahydrobiopterin (BH4) as well as reduced conversion of phenylalanine to tyrosine in the cerebrospinal fluid, which are associated with decreased dopamine in the brain.[6]

Fatigue[edit | edit source]

The dopamine imbalance hypothesis of fatigue in neurological disorders states that:

"...fatigue arises [in neurological disease] due to a dopamine imbalance in the central nervous system"[7]

The dopamine hypothesis seeks to explain fatigue in multiple sclerosis, Parkinson's disease, HIV and chronic fatigue syndrome and focuses on the role of central fatigue, which can be physical or mental.[7]

Chronic fatigue syndrome[edit | edit source]

Studies have found lower levels of the dopamine precursor tyrosine[8] and reduced activation in the basal ganglia[9][10], 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.[11][12][13][14]

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.[15]

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.[16]

Dopaminergic neurons are thought to play a role in epileptic seizures arising from the limbic system.[17]

Altering dopamine levels[edit | edit source]

Mice fed a ketogenic diet had increased activity of dopaminergic neurons.[18]

See also[edit | edit source]

Learn more[edit | edit source]

References[edit | edit source]

  1. ↑ 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.
  2. ↑ 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.
  3. ↑ Bordon, Yvonne (February 2015). "Dopamine blocks inflammasome activation". Nature Reviews Immunology. 15 (2): 69–69. doi:10.1038/nri3817. ISSN 1474-1741.
  4. ↑ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856781/
  5. ↑ http://www.nature.com/nrd/journal/v10/n4/full/nrd3422.html
  6. ↑ 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.
  7. ↑ 7.0 7.1 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.
  8. ↑ 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.
  9. ↑ http://www.fasebj.org/cgi/content/meeting_abstract/26/1_MeetingAbstracts/1035.20
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ http://www.ncbi.nlm.nih.gov/pubmed/17610577
  14. ↑ http://www.ncbi.nlm.nih.gov/pubmed/24449585
  15. ↑ Ciattei, Jennifer. "Causes of Restless Legs Syndrome (RLS) | The Johns Hopkins Center for Restless Legs Syndrome". hopkinsmedicine.org. Retrieved May 28, 2020.
  16. ↑ 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.
  17. ↑ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774988/
  18. ↑ http://www.ncbi.nlm.nih.gov/pubmed/24769322
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