抗Lingo-1抗体对抑郁症伴认知障碍大鼠海马DG区少突胶质细胞作用的研究

Effect of anti-Lingo-1 antibody on oligodendrocytes in the hippocampal dentate gyrus in rats with depression and cognitive impairment

摘要:

目的：探讨抗Lingo-1抗体对抑郁症伴认知障碍大鼠海马齿状回（dentate gyrus，DG）区少突胶质细胞的作用。方法：4~6周清洁级雄性SD大鼠适应性喂养1周后，随机分为对照组（10只）和建模组（60只），建立慢性不可预知性应激（chronic unpredictable stress，CUS）抑郁症模型，为期4周。利用糖水偏好实验筛选出成模大鼠（23只），随机分为CUS组（12只）及Anti-Lingo-1组（11只）。运用Morris水迷宫评估对照组，CUS组和抗Lingo-1组的行为学水平，采用体视学方法计算各组大鼠海马DG区的少突胶质细胞数量。结果：应激4周和抗Lingo-1抗体治疗3周后，Morris水迷宫实验中，与对照组（3.4±0.2）相比，CUS组（2.4±0.2）大鼠Morris水迷宫第6天穿越平台次数明显降低（F=20.049, P=0.004）；与CUS组比较，抗Lingo-1组（4.3±0.3）大鼠穿台次数明显增加（F=20.049, P=0.000）。体视学研究结果表明，与对照组[（4.9±1.1）×104]比较，CUS组[（3.1±1.3）×104]大鼠海马DG区少突胶质细胞数量明显减少（F=8.747, P=0.026）；与CUS组比较，Anti-Lingo-1组[（6.1±1.1）×104]大鼠海马DG区少突胶质细胞数量明显增加（F=8.747, P=0.001）。结论：抗Lingo-1抗体可以改善抑郁症大鼠的认知障碍，抗Lingo-1抗体对抑郁症伴认知障碍大鼠海马DG区少突胶质细胞的作用可能是抗Lingo-1抗体改善抑郁症大鼠认知障碍的重要形态学基础之一。

Abstract:

Objective: To investigate the effect of anti-Lingo-1 antibody on oligodendrocytes in the hippocampal dentate gyrus (DG) in rats with depression and cognitive impairment. Methods: After 1 week of adaptive feeding, 70 clean male Sprague-Dawley rats aged 4-6 weeks were randomly divided into control group with 10 rats and model group with 60 rats. A rat model of depression with chronic unpredictable stress (CUS) was established for 4 weeks. The sucrose preference test was used to screen out 23 model rats, and then these rats were randomly divided into CUS groups with 12 rats and anti-Lingo-1 group with 11 rats. The Morris water maze was used to assess the behavioral level of the control group, the CUS group, and the anti-Lingo-1 group, and the stereological method was used to calculate the number of oligodendrocytes in the hippocampal DG for all groups. Results: After 4 weeks of CUS stimulation, compared with the control group, the CUS group had a significant reduction in the number of platform crossings on day 6 (2.4±0.2 vs 3.4±0.2, F = 20.049, P = 0.004); after 3 weeks of anti-Lingo-1 antibody treatment, the anti-Lingo-1 group had a significant increase in the number of platform crossings compared with the CUS group (4.3±0.3 vs 2.4±0.2, F = 20.049, P = 0.000). The stereological results showed that compared with the control group, the CUS group had a significant reduction in the number of oligodendrocytes in the hippocampal DG [(3.1±1.3)×104 vs (4.9±1.1)×104, F = 8.747, P = 0.026); compared with the CUS group, the anti-Lingo-1 group had a significant increase in the number of oligodendrocytes in the hippocampal DG [(6.1±1.1)×104 vs (3.1±1.3)×104, F = 8.747, P = 0.001). Conclusion: Anti-Lingo-1 antibody can improve cognitive impairment in rats with depression. The effect of anti-Lingo-1 antibody on oligodendrocytes in the hippocampal DG in rats with depression and cognitive impairment might be one of the important structural bases for anti-Lingo-1 antibody in improving cognitive impairment in rats with depression.