Arc在癫痫和抑郁合并症模型大鼠海马中的表达模式

IF 3.5 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin Pub Date : 2025-02-27 DOI:10.1016/j.brainresbull.2025.111267

Shiqian Yu, Hu Tuo, Baozhen Yao, Haiju Zhang, Fang Liu

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Expression pattern of Arc in the hippocampus of a rat model of epilepsy and depression comorbidity

Background

Two key factors associated with the comorbidity of epilepsy and depression (EAD), activity regulated cytoskeletal protein (Arc) and homer protein homolog 1 (Homer1), were previously identified by our group through bioinformatics methods (Yu et al., 2022). The expression of Arc and Homer1 were verified through animal experiments.

Methods

Six-week-old male specific pathogen-free grade Sprague Dawley rats (weighing 200 ± 20 g) received intraperitoneal injection of lithium chloride (LiCl)-pilocarpine for status epilepticus (SE) induction. SE was terminated after 30 min by intraperitoneal injection of diazepam, and spontaneous SE in rats was monitored by video for 2 weeks. The control group (Con group) was injected with an equal dose of sterile normal saline. Subsequently, EAD rats (EAD group) were selected from rat models of LiCl-pilocarpine-induced chronic epilepsy according to the immobility time of the forced swimming test on day 14 after LiCl-pilocarpine induced epilepsy. The remaining rats were included in the epilepsy group (EP group). Depression-like behaviors were evaluated using sucrose preference, open-field, and forced swimming tests. Body weight, sucrose preference percentage, the total distance of the open-field test, the average speed, the number of upright times, and the immobility time of the forced swimming test were assessed 14 and 28 days after LiCl-pilocarpine induced epilepsy. Rats in the EAD and EP groups were monitored by video for 2 weeks, and the frequency, grade, and duration of chronic spontaneous epileptic seizures were recorded. Epileptic seizures were compared between the EAD and EP groups. The expression of activity-regulated cytoskeletal protein (Arc) and Homer protein homolog 1 (Homer1) in the hippocampus of each group was detected by real-time quantitative PCR and western blot analysis. The fluorescence intensity of Arc in the hippocampus of each group was detected by immunofluorescence (IF) assay.

Results

Compared with the Con and EP groups, rats in the EAD group exhibited a decreased body weight on day 28, a significant decrease in sucrose preference percentage on days 14 and 28, significantly extended immobility time, and significantly reduced total travel, average speed, the number of upright times. No significant differences in the number, grade, and duration of seizures were observed between the EAD and EP groups. Meanwhile, the expression level of Arc in the hippocampus was significantly decreased in the EAD group compared with the Con and EP groups; however, the expression level of Homer1 showed no significant change. IF results showed that Arc was mainly expressed in the cytoplasm, and the fluorescence intensity of Arc in hippocampal CA1, DG, and CA3 was lower in the EAD group than in the Con and EP groups.

Conclusions

The expression of Arc in the hippocampal tissue of EAD rats is significantly decreased, suggesting that Arc is associated with EAD.

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来源期刊

Brain Research Bulletin 医学-神经科学

CiteScore

6.90

自引率

2.60%

发文量

253

审稿时长

67 days

期刊介绍： The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.