在临床上，肿瘤压迫、外伤、手术损伤和其他类型的损伤均可引起下丘脑损伤，导致各种类型的下丘脑功能障碍。催产素释放受损可导致认知障碍，并影响下丘脑损伤后的预后和长期生活质量。在雄性动物中检测到下丘脑损伤引起的认知功能障碍。测量行为参数以评估下丘脑-垂体柄病变引起的认知功能障碍的特征。收集大脑进行高通量RNA测序和免疫染色，以确定海马区域的病理生理变化，这些变化与相应下丘脑区域损伤后的认知功能高度相关。通过转录组分析，我们证实了下丘脑损伤后催产素神经元的丧失，以及补充催产素后下丘脑诱导的认知功能障碍的逆转。此外，下丘脑损伤后观察到ERK信号通路过度激活和海马区β-淀粉样蛋白沉积，抑制ERK信号通路过度激活后认知功能恢复。我们的研究结果表明，下丘脑损伤后的认知功能障碍可能是由于催产素神经元数量减少导致海马区 ERK 过度磷酸化引起的，进而导致 β-淀粉样蛋白沉积。© 2024。作者。

In clinical settings, tumor compression, trauma, surgical injury, and other types of injury can cause hypothalamic damage, resulting in various types of hypothalamic dysfunction. Impaired release of oxytocin can lead to cognitive impairment and affect prognosis and long-term quality of life after hypothalamic injury. Hypothalamic injury-induced cognitive dysfunction was detected in male animals. Behavioral parameters were measured to assess the characteristics of cognitive dysfunction induced by hypothalamic-pituitary stalk lesions. Brains were collected for high-throughput RNA sequencing and immunostaining to identify pathophysiological changes in hippocampal regions highly associated with cognitive function after injury to corresponding hypothalamic areas. Through transcriptomic analysis, we confirmed the loss of oxytocin neurons after hypothalamic injury and the reversal of hypothalamic-induced cognitive dysfunction after oxytocin supplementation. Furthermore, overactivation of the ERK signaling pathway and β-amyloid deposition in the hippocampal region after hypothalamic injury were observed, and cognitive function was restored after inhibition of ERK signaling pathway overactivation. Our findings suggest that cognitive dysfunction after hypothalamic injury may be caused by ERK hyperphosphorylation in the hippocampal region resulting from a decrease in the number of oxytocin neurons, which in turn causes β-amyloid deposition.© 2024. The Author(s).