PRELIMINARY EVALUATION OF KYNA ON ATTENUATING NEUROCOGNITIVE IMPAIRMENTS IN HIV-1 GP120 TRANSGENIC MICE

Abstract

Intro: HIV-associated neurocognitive disorders (HAND) are common complications in central nervous system (CNS), mainly cause HIV dementia and lead to serious social economic load. In our preliminary works, HIV-1 gp120 transgenic mice (Tg mice) were successfully established for simulating the HAND. In addition, we found that α7nAChR plays the key regulatory role in the pathogenesis of HAND, while tryptophan-derived kynurenic acid (KYNA) has been reported for its antagonism on α7nAChR. In this study, we aim to determine the protective effect of KYNA on neurocognitive impairments in Tg mice. Methods: Tg mice were involved and divided into control and tryptophan groups (n=6). Mice in tryptophan group were fed with 0.1% tryptophan for 7 days, ELISA was applied to quantitatively detect the KYNA levels in cerebrospinal fluid samples. Twenty Tg mice were involved for neurocognitive evaluation. Control group (n=10) was fed with normal saline while tryptophan group was fed with 0.1% tryptophan for one month. After training, two groups of mice were taken out for evaluation with Morris Water Maze. Findings: In tryptophan group, KYNA level in brain is higher than that in control group (P<0.05). After training of Morris water maze, we observed that Tg mice spent more time and longer distances to find the platform than WT mice (P<0.05). On another hand, Tg mice in tryptophan group spent less time finding platforms than Tg mice in control group (P<0.05). These results suggested that treatment with tryptophan attenuated neurocognitive impairments in Tg mice. Conclusion: Tryptophan-feeding increases KYNA levels both in cerebrospinal fluid and brain tissues of mice and attenuates neurocognitive impairments on HIV-1 gp120 transgenic mice.