Chronic exposure to stressful conditions may affect spatial learning and memory abilities and the brain structure, and disruptions in oligodendrocyte function may cause cognitive dysfunction. Leucine-rich repeat and immunoglobulin-like domain-containing protein 1 (LINGO-1) is a potent negative regulator of oligodendrocytes and axon myelination. However, the questions we sought to answer in this study are whether hippocampal oligodendrocytes are involved in the pathological process of spatial learning and memory impairments induced by chronic stress (CS) and whether antibodies targeting LINGO-1 improve stress-induced spatial learning and memory impairments by protecting the hippocampal oligodendrocytes in stressed rats. After 4 weeks of CS, rats were randomly divided into either the CS standard group or anti-LINGO-1 group. The anti-LINGO-1 group was treated with an anti-LINGO-1 antibody (8 mg/kg) for 3 weeks; all rats were assessed in the Morris water maze. Immunohistochemical staining and modern stereological methods were used to precisely quantify the total number of 2′,3′-cyclic nucleotide 3′-phosphodiesterase-positive (CNPase⁺) oligodendrocytes in each subregion of the hippocampus. At the behavioural level, after three weeks of treatment, the anti-LINGO-1 group displayed significantly more platform crossings in the Morris water maze test than the CS standard group. The total swimming distance and swimming speed were not significantly different. In the open field test, the percentage of distance travelled in the central region did not differ between the CS standard group and control group or between the anti-LINGO-1 group and the CS standard group. Unbiased stereological analyses revealed significantly greater total numbers of CNPase⁺ cells in the CA3 and dentate gyrus (DG) areas of the hippocampus in the anti-LINGO-1 group than in the CS standard group. A significant difference in the total number of CNPase⁺ cells was not observed in the hippocampal CA1 region between the anti-LINGO-1 and CS standard groups. Based on the results of the present study, the anti-LINGO-1 antibody alleviated spatial memory impairments and protected oligodendrocytes in the hippocampus of chronically stressed rats.

长期处于压力状态可能会影响空间学习和记忆能力以及大脑结构，少突胶质细胞功能的破坏可能会导致认知功能障碍。富含亮氨酸重复和免疫球蛋白样结构域的蛋白 1 (LINGO-1) 是少突胶质细胞和轴突髓鞘形成的有效负调节因子。然而，我们在本研究中试图回答的问题是海马少突胶质细胞是否参与慢性压力 (CS) 引起的空间学习和记忆障碍的病理过程，以及针对 LINGO-1 的抗体是否可以改善压力引起的空间学习和记忆障碍通过保护应激大鼠的海马少突胶质细胞。CS 4周后，将大鼠随机分为CS标准组或抗LINGO-1组。抗LINGO-1组用抗LINGO-1抗体（8mg/kg）治疗3周；所有大鼠均在 Morris 水迷宫中进行评估。使用免疫组织化学染色和现代立体学方法精确量化 2',3'-环核苷酸 3'-磷酸二酯酶阳性 (CNPase⁺ ) 海马每个亚区的少突胶质细胞。在行为层面，治疗三周后，抗LINGO-1组在Morris水迷宫测试中比CS标准组表现出明显更多的平台穿越。总游泳距离和游泳速度没有显着差异。在旷场试验中，CS标准组和对照组之间或抗LINGO-1组和CS标准组之间在中心区域行驶的距离百分比没有差异。无偏见的体视学分析显示，与 CS 标准组相比，抗 LINGO-1 组海马 CA3 和齿状回 (DG) 区域的 CNPase ⁺细胞总数显着更多。CNPase总数的显着差异在抗 LINGO-1 和 CS 标准组之间的海马 CA1 区域中未观察到⁺细胞。根据本研究的结果，抗 LINGO-1 抗体减轻了空间记忆障碍并保护了慢性应激大鼠海马中的少突胶质细胞。