It is appreciated that metabolites generated by the metabolism of tryptophan via the kynurenine pathway (KP) play a role in neurobiological diseases and processes (R Schwarcz and TW Stone, 2017). However, there is a need to better understand the cellular expression of key enzymes of the KP, the ability of metabolites to cross the blood-brain barrier, and the biological effects of these metabolites in the brain.
A recent study published by Dr. Korrapati V. Sathyasaikumar et al. in Antioxidants investigated the expression of kynurenine 3-monooxygenase (KMO) in the brain of mice. Previously microglia were considered to be the predominate cell type that expresses KMO. In this study researchers chemically depleted microglia through a PLX5622 infused diet. First, researchers confirmed the loss/reduction of microglia by investigating microglia specific markers and noted 89%-97% decreases across all five markers. Interestingly, KMO expression and activity remained unchanged in the PLX5622 fed mice suggesting that another cell type could contribute to the generation of 3-hydroxykynurenine (3-HK) within the brain. To investigate the expression of KMO further, the researchers isolated astrocytes, neurons, and microglia from murine brain tissue and investigated KMO mRNA and protein expression. Microglia and neurons, but not astrocytes, express KMO at the level of mRNA and protein. This finding is important since the proportion of neurons outweighs that of microglia within the brain. In fact, this study attributed neurons with nearly 30% of the proportion of cells isolated and microglia making up for 15%. Furthermore, they demonstrated that KMO activity was significantly elevated in neurons compared with microglia. Taken together, neurons likely play a bigger role in the generation of 3-HK than once was perceived. Further studies should look into region- and neuron-specific expression of KMO, as well as looking at other cell types such as oligodendrocytes.