Translocation of High Mobility Group Box 1 From the Nucleus to the Cytoplasm in Depressed Patients With Epilepsy

• Published in: ASN neuro 2022-01, Vol.14, p.175909142211366-17590914221136662
• Main Authors: Li, Xiao-Li, Wang, Shu, Tang, Chong-Yang, Ma, Hao-Wei, Cheng, Zi-Zhang, Zhao, Meng, Sun, Wei-Jin, Wang, Xiong-Fei, Wang, Meng-Yang, Li, Tian-Fu, Qi, Xue-Ling, Zhou, Jian, Luan, Guo-Ming, Guan, Yu-Guang
• Format: Article
• Language: English
• Subjects: Astrocytes; Comorbidity; Cytoplasm; Drug resistance; Enzyme-linked immunosorbent assay; Epilepsy; High mobility group proteins; Hippocampus; HMGB1 protein; Immunofluorescence; Inflammation; Mental depression; Mobility; Neurons; Original Paper; Sclerosis; Temporal lobe
• ISSN: 1759-0914; 1759-0914
• 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 (n = 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.