Abstract: Objective: To investigate the effect of nicotinamide riboside (NR), a nutritional supplement, on improving depression-like behavior and intestinal mucosal permeability in mice exposed to alcohol. Methods: Thirty male C57BL/6J mice were randomly divided into three groups (with 10 mice in each group). The mice from the control and model groups were given on a daily basis 0.2 mL of normal saline intragastrically, while the mice from the NR intervention group were administered with 400 mg/kg mb of NR intragastrically every day. The mice in the model and NR treatment groups were given freshly prepared 15% alcohol solution from 8:00 a.m. to 4:00 p.m. Monday to Thursday every week, and had free access to tap water from 4:00 p.m. to 8:00 a.m. the next day, whereas the mice in the control group were given tap water all day long. Every Friday and Saturday, the mice from the three groups were cut off from any water source and every Sunday, the mice from three groups were once again given tap water to drink freely. The mice in all these groups were allowed to eat freely throughout the experiment, which lasted for 10 weeks. The depression-like behavior of the mice was evaluated by open field test, sucrose preference test and forced swimming test. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of the CA1 region of the hippocampus of mice. The serum levels of brain-derived neurotrophic factor (BDNF) and lipopolysaccharide (LPS) were measured by enzyme-linked immunosorbent assay. The ultrastructures of intercellular linkages in jejunum and colon tissues were examined using a transmission electron microscope. The permeability of jejunum and colon tissues was observed by tracer test. Western blotting was used to detect the expression of the tight junction proteins, occludin and ZO-1, in jejunum and colon tissues. Results: In the open field test, the total distance and the time spent in the central area of the model group were decreased compared with the control and NR groups. Similarly, the sucrose preference of the mice in the model group was significantly reduced compared with the control and NR groups). The immobility time in the forced swim test was ((168.6 ± 34.4) s) in the model group, which was significantly longer than the control and NR groups (P < 0.05). The results of HE staining showed that NR intervention improved neuronal damage induced by alcohol exposure to some extent. The level of serum BDNF of mice in the model group was (438.9 ± 46.7) pg/mL, which was significantly reduced compared with the control group ((638.1 ± 77.3) pg/mL) (P < 0.05). After NR intervention, the serum BDNF level was (735.7 ± 55.7) pg/mL, which was significantly higher than that of the model group (P < 0.05). The level of serum LPS in model group was (22.5 ± 1.8) ng/mL, which was significantly higher than that in control group ((13.2 ± 3.0) ng/mL) (P < 0.05). After NR intervention, serum LPS level of mice decreased to (17.5 ± 0.3) ng/mL. Compared with the control group, the intercellular junction of jejunum and colon tissues in the model group was changed abnormally, and the permeability was increased. After NR intervention, the intercellular junction and permeability of jejunum and colon tissues were significantly improved and repaired. Western blot results showed that the expression levels of occludin and ZO-l of the model group were significantly lower than those of the control group (P < 0.05). After NR intervention, the expression levels of occludin and ZO-l increased to varying degrees. Conclusion: Nicotinamide ribose can effectively alleviate depression-like behavior in mice exposed to alcohol, and its underlying mechanism may be related to the protective effect of NR on intestinal mucosal permeability.

Key words: nicotinamide riboside, alcohol, mice, depression-like behavior, intestinal mucosal barrier