Relationships between Pregnancy and Vitamin B-6 Nutriture on Brain 3-Hydroxykynurenine Concentrations in Mice

Abstract

The kynurenine (KYN) pathway of tryptophan metabolism produces several neuroactive metabolites, including 3-hydroxykynurenine (3HK). The pathway is subject to regulation by a number of effectors including pregnancy and availability of vitamin B-6. Vitamin B-6 depleted humans and animals excrete abnormally high concentrations of KYN metabolites in urine. In pregnancy, vitamin B-6 deficiency is commonly seen, and tryptophan metabolism is often found to be altered. We measured concentrations of 3HK in brains of DBA/2Ibg and A/Ibg mice as functions of pregnancy and dietary level of vitamin B-6. Pregnant DBA mice are more susceptible to flurothyl-induced seizures than controls, pregnant A mice are not. Significant elevations of 3HK were found in brains of pregnant mice, and the increases were greater in the pregnancy-associated seizure prone DBA, than in the A mice. In the A mice, brain 3HK concentrations were negatively correlated with dietary vitamin B-6 levels, as expected; however, in the DBA mice these correlations were positive, indicating an unusual response to vitamin B-6 restriction. The accumulation of a cytotoxic, excitatory metabolite, 3HK, in brain may contribute to the increased seizure susceptibility of susceptible pregnant mice, perhaps though its effects as an endogenous modulator of excitatory amino acid receptor systems.

Keywords:

• 3-Hydroxykynurenine
• Kynurenine pathway
• Mice
• pregnancy
• seizures
• Vitamin B-6