Kynurenines and brain development

The mechanisms by which environmental factors such as stress, infection, or inflammation could affect the early brain development of the embryo are largely unknown. One metabolic pathway that could be important is the kynurenine pathway for the oxidative metabolism of tryptophan, since it is activated by each of these factors and it generates an agonist (quinolinic acid) and an antagonist (kynurenic acid) at glutamate receptors sensitive to N-methyl-d-aspartate. These receptors are known to be important in neurogenesis, neuron precursor migration, neurite formation, axon guidance, and synapse formation. This review summarizes the effects of inhibiting the pathway, during pregnancy in rats, on brain development in the neonates and adult offspring. The widespread changes in protein expression and localization with changes in neuronal excitability and plasticity reinforce the view that kynurenines play a significant role in early brain development and may be the substrates on which subsequent cues act to enhance or restrict behavioral and cognitive function