The relationship between thiamin, folic acid and cognitive function in a rat model of uremia

Abstract

End-stage renal disease is a worldwide health burden, but the pathogenesis of uremia-associated cognitive impairment (CI) is poorly recognized. We hypothesized that uremia brings about deficiency of thiamin and folic acid and causes CI by inducing oxidative stress. Therefore, 24 Sprague-Dawley rats were randomly divided into two groups: a 5/6 nephrectomy group (n = 12) and a sham-operated group (n = 12). The Morris water maze was used to assess the cognitive function eight weeks post-surgery, and serum levels of thiamin, folic acid and homocysteine were detected subsequently. Brain and kidney tissues were collected for pathological examination and 8-Hydroxy-2’-deoxyguanosine (8-OHdG) immunochemistry staining. Results showed that the escape latency on training days 1-2 was longer, and the time in quadrant IV on experimental day 6 was significantly shorter in 5/6 nephrectomy group. Meanwhile, the uremic rats showed decreased thiamin, folic acid and increased homocysteine. We also found the time in quadrant IV was positively correlated with thiamin and folic acid level, while negatively correlated with the blood urea nitrogen and 8-OHdG positive cell proportion. Furthermore, in 5/6 nephrectomy group, the hippocampal neuron count was significantly reduced, and a greater proportion of 8-OHdG positive cells were detected. Pretreating LPS-stimulated rat microglial cells with thiamin or folic acid in vitro alleviated the inflammatory impairment in terms of cell viability and oxidative stress. In summary, we applied a uremic rat model and proved that uremia causes serum thiamin and folic acid deficiency, homocysteine elevation, along with neuron reduction and severe oxidative stress in hippocampus, finally leading to CI.

Keywords:

• End-stage renal disease
• uremic rat model
• cognitive impairment
• vitamin B
• oxidative stress

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was supported by the 2017 Clinical Research Innovation Training Fund of Renji Hospital, School of Medicine, Shanghai Jiao Tong University under Grant PYIII-17-028, the 2019 Special fund for Clinical Medical Research of the Chinese Medical Association under Grant 18020030782; the 2019 Research Seed Fund Training program of Renji Hospital, School of Medicine, Shanghai Jiao Tong University under Grant RJZZ19-004 and the Clinical Research Plan of Shanghai Hospital Development Center under Grant SHDC2020CR4004.