Developmental Exposure to Kynurenine Affects Zebrafish and Rat Behavior

Abstract

Proper nutrition and supplementation during pregnancy and breastfeeding are crucial for the development of offspring. Kynurenine (KYN) is the central metabolite of the kynurenine pathway and a direct precursor of other metabolites that possess immunoprotective or neuroactive properties, with the ultimate effect on fetal neurodevelopment. To date, no studies have evaluated the effects of KYN on early embryonic development. Thus, the aim of our study was to determine the effect of incubation of larvae with KYN in different developmental periods on the behavior of 5-day-old zebrafish. Additionally, the effects exerted by KYN administered on embryonic days 1–7 (ED 1–7) on the behavior of adult offspring of rats were elucidated. Our study revealed that the incubation with KYN induced changes in zebrafish behavior, especially when zebrafish embryos or larvae were incubated with KYN from 1 to 72 h post-fertilization (hpf) and from 49 to 72 hpf. KYN administered early during pregnancy induced subtle differences in the neurobehavioral development of adult offspring. Further research is required to understand the mechanism of these changes. The larval zebrafish model can be useful for studying disturbances in early brain development processes and their late behavioral consequences. The zebrafish-medium system may be applicable in monitoring drug metabolism in zebrafish.

A Review on the Role and Function of Cinnabarinic Acid, a “Forgotten” Metabolite of the Kynurenine Pathway

“…Compared especially to KYNA, based on the data of Majewski et al [ 98 ], CA seems to be teratogenic. However, this is a single study that needs replication to make a proper conclusion, considering that, for example, the observations for L-KYN of Majewski et al [ 98 ] are not in agreement with those of Marszalek-Grabska et al [ 99 ].…”

Fetal Sex as Moderating Factor for the Relationship Between Maternal Childhood Trauma and Salivary Kynurenic Acid and Tryptophan in Pregnancy: A Pilot Study

“… 18 In addition, our recent study has shown that administering kynurenine to pregnant female rats at embryonic days 1 to 7 or exposure of zebrafish larvae to kynurenine leads to changes in neurobehavioral development. 19 The effects of kynurenine administration may have long-term consequences, as animals exposed to kynurenine during the embryonic period or lactation showed behavioral abnormalities in adulthood. 19 , 20 …”

“… 19 The effects of kynurenine administration may have long-term consequences, as animals exposed to kynurenine during the embryonic period or lactation showed behavioral abnormalities in adulthood. 19 , 20 …”