Relevant to PEM - excercise and serotonin metabolism

[natasa778]

apologies if this has been discussed before ... there are several threads on inflammation and serotonin metabolism and related issues so wasn't sure where to post.

Adv Exp Med Biol. 2003;527:531-5.
Tryptophan metabolism was accelerated by exercise in rat.

Ito Y, Yonekura R, Maruta K, Koike T, Nakagami Y, Shibata K, Saito K, Nagamura Y.
Department of Physiology, School of Health Sciences, Fujita Health University, Toyoake Aichi, 470-1192, Japan. yasitoh@fujita-hu.ac.jp
Abstract

We have already reported that exercise activates kynurenine pathway. But, the mechanism for this activation by exercise is still unclear. Kynurenine is metabolized to NAD, which is an essential factor for energy metabolism. In this study, exercise on treadmill was loaded to rats until all-out and tryptophan metabolites and tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) activities were determined in the blood, livers, and macrophages, respectively, in the exercise-loaded rats. The mean values of serum tryptophan concentration decreased from 92.6 +/- 6.0 nmol/ml to 52.4 +/- 10.2 nmol/ml (p<0.05) just after treadmill load. The serum kynurenine concentration had increased from 2.06 +/- 0.25 nmol/ml to 3.08 +/- 0.62 nmol/ml (p<0.005). And whole blood NAD concentration increased from 68.8 +/- 14.6 nmol/ml to 77.9 +/- 19.1 nmol/ml (p<0.005). These results showed that exercise activated the kynurenine pathway of tryptophan metabolism and made NAD which will be concerned with energy metabolism in mitochondria. Tryptophan-NAD pathway was initiated by cleavage of indole ring of tryptophan by TDO in the liver and IDO in many organs. We had also found that the exercise increase IDO activity of macrophages, but not TDO activity.

btw indoleamine 2,3-dioxygenase (IDO) is already overexpressed in chronic infectious/inflammatory states (via interferon), so most likely implicated in ME. Wondering what happens in the scenario above in cases where this pathway is already dysfunctional or stressed or somehow blocked?

So instead of more energy (NAD) following excercise because of this blockage/dysfunction in the pathway we get more toxic metabolites of that pathway - kynurenic and quinolinic acids??

High levels of kynurenic acid have been identified in patients suffering from tick-borne encephalitis, schizophrenia and HIV-related illnesses. In all these situations increased levels were associated with confusion and psychotic symptoms.

Quinolinic acid has a potent neurotoxic effect. Studies have demonstrated that quinolinic acid may be involved in many psychiatric disorders, neurodegenerative processes in the brain, as well as other disorders. Within the brain, quinolinic acid is only produced by activated microglia and macrophages

For the brave http://en.wikipedia.org/wiki/File:KP_pathway.jpg

 

[Bob]

I wonder if this in any way might link with the recent 5-HT autoimmunity discussions we've had?
http://forums.phoenixrising.me/inde...robs-bacterial-translocation-in-me-cfs.23198/

 

[xchocoholic]

The mean values of serum tryptophan concentration decreased from 92.6 +/- 6.0 nmol/ml to 52.4 +/- 10.2 nmol/ml (p<0.05) just after treadmill load.

If I read this correctly, we finally know why rats get depressed after running on treadmills.