The impact of folate status to the neuropathy in aged zebrafish

Abstract

Folate as known as vitamin B9 is a water-soluble nutrient which is essential for many physiological functions such as methylation nucleotide synthesis and DNA repair Folate deficiency (FD) had been reported as risk factor for neurological disease such as neuro tube defects and Alzheimer’s disease (AD) The role of FD in AD patients remains unclear In the previous study the deposition of β-amyloid (Aβ) and phosphorylated-tau the pathological hallmarks of AD were observed in the brain of aged FD zebrafish The impaired cognitive ability was also observed in aged FD zebrafish In this study we investigated the impacts of folate status on the neuropathy of aged zebrafish Simultaneously aged zebrafish were tube feeding with either oxidized or reduced forms of folate and evaluated for their cognitive and memory ability Then we measured the folate content in brain and liver also applied immunohistochemistry staining in brain sections and then observed The result showed that the tissue folate content was not significantly changed under the one-hour heat shock treatment but the cognitive and memory ability of FD zebrafish was affected The impairments were partially restored by supplementing with 5-formyltetrahydrofolate (5-CHO-THF) and lower dose (45 ?g) of folic acid (FA) However higher dose (400 ?g) of FA vitamin C and ATP did not exert significant improvement These findings suggested that supplementing with reduced folate and lower dose of FA had protective effect to the cognitive ability of aged zebrafish To enhance the intensity of folate deficiency we extended the heat shock treatment to 14 hours The tissue folate content was significantly decreased in FD and the cognitive ability was also impaired We found that the brain folate content was lower in cognitive ability impaired zebrafish However the result of Aβ deposition by the immunohistochemistry staining showed that there was no significant correlation between Aβ deposition and cognitive ability Hence we thought that the impact of FD on cognitive ability of aged zebrafish might not be due to Aβ deposition In the future the 8-OHdG stain was applied to investigate whether the oxidative stress in brain of zebrafish was affected by FD Moreover to examine the effect of other antioxidants and one-carbon provider on relieving the impairment of cognitive ability

Date of Award	2016 Aug 24
Original language	English
Supervisor	Tzu-Fun Fu (Supervisor)