Departamento de Fisiología y Farmacología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Av. Universidad, No. 940, Ciudad Universitaria, C.P. 20100, Aguascalientes, Aguascalientes, México.
Departamento de Psicología, Centro de Ciencias Sociales y Humanidades, Universidad Autónoma de Aguascalientes, Av. Universidad, No. 940, Ciudad Universitaria, C.P. 20100, Aguascalientes, Aguascalientes, México.
Metab Brain Dis. 2024 Oct;39(7):1447-1458. doi: 10.1007/s11011-024-01413-9. Epub 2024 Aug 23.
Hepatic encephalopathy (HE) is a neuropsychiatric complication of acute liver failure or chronic liver injury. Liver dysfunction impairs ammonia detoxification, allowing it to cross the blood-brain barrier (BBB) and disrupt brain function. The hippocampus becomes a crucial target during elevated ammonia levels, causing spatial memory impairment and decreased learning ability. Leuprolide acetate (LA), a GnRH agonist, has been implicated in neuroprotection and neuroregeneration in several regions of the central nervous system (CNS) including hippocampus. In this study, we aim to evaluate the effects of LA treatment on hippocampus of rats with HE induced by portocaval anastomosis (PCA) trough cognitive tests, histology analysis and expression of neuronal recovery marker proteins, such as neurofilament (NF200) and neurabin II, and astrocyte marker glial fibrillary acidic protein (GFAP). Rats were divided into three groups: SHAM, portocaval anastomosis with saline solution (PCA + SS) and portocaval anastomosis treated with LA (PCA + LA). To evaluate learning and spatial memory elevated T-maze (ETM) and Y-maze test (YMT) were respectively used. Results indicated that LA-treated rats performed significantly better in ETM and YMT than untreated rats. Histological analysis of hippocampus showed increased neuron density, nuclear area, and layer thickness in dentate gyrus of PCA + LA group compared to PCA + SS. Additionally, neurabin II and NF200 expression were higher in LA-treated rats, while GFAP expression was elevated in the PCA + SS group compared to control and PCA + LA groups. In conclusion, LA enhances hippocampal neuron recovery and reduces astrogliosis, suggesting its potential as a therapeutic intervention for attenuating hippocampal damage during HE.
肝性脑病（HE）是急性肝衰竭或慢性肝损伤的神经精神并发症。肝功能障碍会损害氨的解毒作用，使氨能够穿过血脑屏障（BBB）并破坏大脑功能。在氨水平升高的情况下，海马成为一个关键靶点，导致空间记忆障碍和学习能力下降。亮丙瑞林（LA），一种 GnRH 激动剂，已被牵连到包括海马在内的中枢神经系统（CNS）多个区域的神经保护和神经再生中。在这项研究中，我们旨在通过认知测试、组织学分析和神经元恢复标志物蛋白（如神经丝（NF200）和神经连接蛋白 II）和星形胶质细胞标志物胶质纤维酸性蛋白（GFAP）的表达，评估 LA 治疗对门腔静脉吻合术（PCA）诱导的 HE 大鼠海马的影响。大鼠分为三组：SHAM、PCA 加生理盐水（PCA+SS）和 PCA 加 LA（PCA+LA）。为了评估学习和空间记忆，分别使用高架 T 迷宫（ETM）和 Y 迷宫测试（YMT）。结果表明，与未治疗的大鼠相比，LA 治疗的大鼠在 ETM 和 YMT 中表现出显著更好的性能。海马组织学分析显示，与 PCA+SS 组相比，PCA+LA 组齿状回的神经元密度、核面积和层厚度增加。此外，LA 治疗组的神经连接蛋白 II 和 NF200 表达较高，而 PCA+SS 组的 GFAP 表达较对照组和 PCA+LA 组升高。总之，LA 增强了海马神经元的恢复并减少了星形胶质细胞增生，表明其作为减轻 HE 期间海马损伤的治疗干预的潜力。
