Complete list of enriched GOs.

Bovine spastic paresis (BSP) is a progressive neuromuscular disease of unknown origin that causes persistent stiffness of the hind limbs. The symptoms are similar to those of human motor neuron diseases such as primary (PLS) or amyotrophic lateral sclerosis (ALS). BSP occurs worldwide in cattle production with an estimated prevalence of <1%. For Germany, this means that around 20,000 Holstein cattle are affected. BSP is generally considered a hereditary disease, but there is no prevention through breeding programs. As a result, BSP not only affects animal welfare but also leads to economic losses in milk and beef production. Here, we used transcriptomics to analyse the brainstem, spinal cord and affected gastrocnemius muscle tissue of eight animals affected by BSP and eight control animals from slaughterhouses to gain new insights into the molecular mechanisms underlying BSP. We found that the expression of several genes was significantly different in animals affected by BSP compared to control animals. Specific genes for inhibitory neurons were downregulated in the brainstems of the affected animals, namely CCK (cholecystokinin), NPY (neuropeptide Y), and SST (somatostatin). These inhibitory neurotransmitters influence cerebral movement control, among other processes. Furthermore, OOSP2 (oocyte secreted protein 2) was found to be significantly upregulated in the affected animals in all tissues. This expression could best be explained by the presence of T-follicular-helper cells which, through interleukin 21, can trigger a TH-2-dominated immune response and lead to autoimmune encephalitis. Further cases were sampled for confirmation and we detected cell infiltrates of activated microglia and T-cells in the brainstem using immunohistochemistry. Microglial foci were significantly more abundant in animals affected by BSP than control animals. We conclude that BSP is caused by an autoimmune reaction directed against inhibitory interneurons in the brainstem and is due to a combination of genetics and environmental influences. This may result in lost controlling influence on the upper motor neurons via extrapyramidal pathways and therefore triggers the specific symptoms of motor neuron disease.

牛痉挛性轻瘫（Bovine spastic paresis, BSP）是一种病因不明的进行性神经肌肉疾病，会引发后肢持续性僵硬。其症状与人类运动神经元疾病，如原发性侧索硬化（Primary Lateral Sclerosis, PLS）或肌萎缩侧索硬化（Amyotrophic Lateral Sclerosis, ALS）相似。BSP在全球肉牛养殖中均有分布，估计患病率低于1%。以德国为例，约有2万头荷斯坦奶牛（Holstein cattle）受该病影响。BSP通常被认为是遗传性疾病，但目前尚无通过育种计划实现的预防手段。因此，该病不仅损害动物福利，还会给乳品和肉牛生产带来经济损失。本研究采用转录组学（transcriptomics）技术，对8头BSP患病牛与8头来自屠宰场的对照牛的脑干、脊髓以及受影响的腓肠肌组织进行分析，以期揭示BSP潜在的分子机制。研究发现，与对照组相比，患病动物体内多个基因的表达存在显著差异。在患病动物的脑干中，抑制性神经元的特异性基因表达下调，包括胆囊收缩素（cholecystokinin, CCK）、神经肽Y（neuropeptide Y, NPY）以及生长抑素（somatostatin, SST）。这些抑制性神经递质除参与其他生理过程外，还参与大脑的运动调控。此外，研究人员在患病动物的所有检测组织中均发现卵母细胞分泌蛋白2（oocyte secreted protein 2, OOSP2）的表达显著上调。该基因的高表达可通过滤泡辅助性T细胞（T-follicular-helper cells）得到最佳解释：这类细胞可通过白细胞介素21（interleukin 21）触发以TH-2型为主的免疫应答，进而诱发自身免疫性脑炎。研究团队进一步采集更多病例进行验证，并通过免疫组织化学（immunohistochemistry）技术在脑干中检测到活化小胶质细胞（activated microglia）与T细胞的细胞浸润。与对照组相比，BSP患病动物的小胶质细胞灶数量显著更多。本研究得出结论：BSP是由针对脑干抑制性中间神经元的自身免疫反应引发，其发病是遗传与环境因素共同作用的结果。该过程可能通过锥体外系通路削弱对上位运动神经元的调控作用，进而诱发运动神经元疾病的特征性症状。