KYNURENINE NEONATAL ADMINISTRATION COMPROMISES MICE NEUROMOTOR DEVELOPMENT

The scientific community has extensively shown the relationship between early insults and the development of neuropsychiatric disorders such as schizophrenia. Among these insults, gestational and neonatal neuroinflammation stand out. Pro-inflammatory cytokines positively regulate enzymes metabolizing tryptophan, disrupting the kynurenine (KYN) pathway. Several animal studies have described that gestational or neonatal exposure to high doses of KYN can cause long-term behavioral impairments. However, there are still no reports on the immediate effects of this exposure in rodents. Therefore, this study aims to evaluate the changes caused by neonatal KYN exposure on the neuromotor development of mice. Male and female Swiss mice (CEUA/UFRJ no. 120/22) received kynurenine (200 mg/kg i.p.) or PBS twice a day between postnatal days (PND) 7 and 16. Animals' weight and developmental milestones (eye opening, ear canal opening, fur development, and righting reflex) were meticulously monitored throughout this period. Additionally, two motor tests were performed: the hind limb suspension test on PND12 and the wire hanging box test on PND17. Finally, the mortality rate was calculated. No significant differences were observed between groups in weight gain, mortality, and neurodevelopmental markers. In the hind limb suspension test, the KYN group showed a significant reduction in time to fall compared to the control, indicating a decrease in muscle force. This change was also observed in the wire hanging box test when the latency to fall of the animals exposed to KYN was shorter than that of control animals. In summary, our data indicates that exposure to KYN may delay the motor development of the animals, as impairments were identified only perinatally and did not persist until adolescence. Moreover, we can conclude that neonatal KYN administration is a relevant model of neurodevelopmental insult. Acknowledgments: CAPES, FAPERJ, CNPq.