Is oxidative stress stealing your serotonin?

In recent posts, we’ve discussed oxidative stress and the innate systems the body uses to control free radical levels. When these systems are not functioning properly or free radicals are being produced too quickly for the body to keep up, problems start to arise. For example, an increase in free radical levels can affect immune activity and neurotransmitter levels by influencing neurotransmitter synthesis.

Free radicals can stimulate the adaptive immune response. This shift in immune activity can have a drastic effect on the tryptophan pathway and serotonin synthesis.

Figure 1. Immune upregulation can shunt tryptophan away from the serotonin pathway and into the kynurenine pathway.

Figure 1. Immune upregulation can shunt tryptophan away from the serotonin pathway and into the kynurenine pathway.

During the adaptive immune response, there is an increase in pro-inflammatory cytokines. One of the functions of these immune messengers is to increase activity of the enzyme indoleamine 2,3-deoxygenase (IDO) (Figure 1). The increase in IDO activity shunts tryptophan away from the serotonin pathway and into the kynurenine pathway. One purpose of this shift is to convert kynurenine to kynurenic acid, which is neuroprotective. However, kynurenine can also be converted to quinolinic acid, which is neurodegenerative.

A possible result of shunting tryptophan down the kynurenine pathway is lower serotonin levels. When IDO activity is increased, there’s less tryptophan available for making serotonin. Low serotonin levels have been associated with clinical symptoms such as depression, insomnia, and anxiety.

As these connections show, it is important to consider the interactions between systems when designing interventions. Assessing neurotransmitter levels and immune activity can help identify a patient’s unique imbalances to help create personalized therapies. Be sure to check back next week to learn how oxidative stress affects catecholamine (norepinephrine, dopamine, and epinephrine) synthesis.

References:
Anisman, A. (2009). Cascading effects of stressors and inflammatory immune system activation: implications for major depressive disorder. J Psychiatry Neurosci, 34(1): 4-20.
Korbecki, J, et al. (2013). The effect of reactive oxygen species on the synthesis of prostanoids from arachidonic acid. J Physiol Pharmacol, 64(4): 409-21.
Sutti, S, et al. (2013). Adaptive immune responses triggered by oxidative stress contribute to hepatic inflammation in NASH. Hepatology, Epub ahead of print.
Wichers, M., Maes, M. (2004). The role of indoleamine 2,3-dioxygenase (IDO) in the pathophysiology of interferon-α-induced depression. J Psychiatry Nerosci, 29(1): 11-17.
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3 Responses to Is oxidative stress stealing your serotonin?

  1. Pingback: Tetrahydro…what? It’s essential to understand the whole neurotransmitter pathway | The NEI Connection

  2. Pingback: Tips For Keeping the Winter Blues At Bay | Healthtalkonpoint

  3. Pingback: Oxidative stress? Let’s take a look at DOPAC… | The NEI Connection

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