Department of Neurology, Affiliated ZhongDa Hospital, Southeast University, Nanjing, China.
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
ASN Neuro. 2022 Jan-Dec;14:17590914221136662. doi: 10.1177/17590914221136662.
Depression is a common psychiatric comorbidity in patients with epilepsy, especially those with temporal lobe epilepsy (TLE). The aim of this study was to assess changes in high mobility group box protein 1 (HMGB1) expression in epileptic patients with and without comorbid depression. Sixty patients with drug-resistant TLE who underwent anterior temporal lobectomy were enrolled. Anterior hippocampal samples were collected after surgery and analyzed by immunofluorescence ( = 7/group). We also evaluated the expression of HMGB1 in TLE patients with hippocampal sclerosis and measured the level of plasma HMGB1 by enzyme-linked immunosorbent assay. The results showed that 28.3% of the patients (17/60) had comorbid depression. HMGB1 was ubiquitously expressed in all subregions of the anterior hippocampus. The ratio of HMGB1-immunoreactive neurons and astrocytes was significantly increased in both TLE patients with hippocampal sclerosis and TLE patients with comorbid depression compared to patients with TLE only. The ratio of cytoplasmic to nuclear HMGB1-positive neurons in the hippocampus was higher in depressed patients with TLE than in nondepressed patients, which suggested that more HMGB1 translocated from the nucleus to the cytoplasm in the depressed group. There was no significant difference in the plasma level of HMGB1 among patients with TLE alone, TLE with hippocampal sclerosis, and TLE with comorbid depression. The results of the study revealed that the translocation of HMGB1 from the nucleus to the cytoplasm in hippocampal neurons may play a previously unrecognized role in the initiation and amplification of epilepsy and comorbid depression. The direct targeting of neural HMGB1 is a promising approach for anti-inflammatory therapy.
抑郁症是癫痫患者常见的精神共病，尤其是颞叶癫痫（TLE）患者。本研究旨在评估伴有和不伴有共病抑郁症的癫痫患者中高迁移率族蛋白 B1（HMGB1）表达的变化。纳入了 60 例接受前颞叶切除术的耐药性 TLE 患者。术后采集前海马样本，通过免疫荧光法进行分析（ = 7/组）。我们还评估了 TLE 患者伴海马硬化中 HMGB1 的表达，并通过酶联免疫吸附试验测量血浆 HMGB1 水平。结果显示，28.3%（17/60）的患者伴有共病抑郁症。HMGB1在前海马的所有亚区均广泛表达。与仅 TLE 患者相比，TLE 伴海马硬化和 TLE 伴共病抑郁症患者的 HMGB1-免疫反应性神经元和星形胶质细胞的比例均显著增加。TLE 伴抑郁患者海马中细胞质与核 HMGB1 阳性神经元的比值高于非抑郁患者，这表明在抑郁组中 HMGB1 更多地从核转移到细胞质。仅 TLE 患者、TLE 伴海马硬化患者和 TLE 伴共病抑郁症患者之间的血浆 HMGB1 水平无显著差异。研究结果表明，HMGB1 从海马神经元核内转移到细胞质可能在癫痫和共病抑郁症的发生和放大中发挥了以前未被认识的作用。针对神经 HMGB1 的直接靶向治疗可能是一种有前途的抗炎治疗方法。
