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突触相关蛋白GAP-43、PSD95、SYN在癫痫共病抑郁大鼠额前皮质中的表达
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Abstract:
目的：检测癫痫共病抑郁大鼠额前皮质神经生长相关蛋白43 (GAP43)、突触后致密蛋白95 (PSD95)及突触素(SYN)的表达情况，探讨额前皮质突触相关蛋白的表达变化在癫痫共病抑郁发病中的作用。方法：选取成年雌性SD大鼠进行实验，采用氯化锂–匹鲁卡品法建立癫痫模型，使用Racine评分标准判断癫痫发作等级。抑郁模型采用孤养法结合慢性不可预见中等应激刺激(Chronic Unpredictable Mild Stress, CUMS)方案，在癫痫造模14天后进行抑郁筛选，按照体重测量、蔗糖溶液偏好率及旷场实验评估大鼠的抑郁情绪，由此分为癫痫共病抑郁组、癫痫组，设置正常组及抑郁组作为对照。应用免疫组织化学染色法检测各组大鼠额前皮质GAP43、PSD95及SYN蛋白的表达情况。结果：在SYN的表达中，与正常组相比，其他各组的SYN表达均减少(P < 0.05)；而与癫痫组相比，抑郁组及共病组SYN表达减少(P < 0.05)；在PSD95表达中，与正常组相比，抑郁组及共病组表达减少(P < 0.05)；与癫痫组相比，抑郁组及共病组PSD95减少(P < 0.05)。正常组GAP43的表达最多(P < 0.05)；而与抑郁组相比，共病组表达降低(P < 0.05)。结论：癫痫共病抑郁大鼠额叶突触相关蛋白GAP-43、SYN、PSD95免疫阳性细胞表达降低可能与癫痫大鼠抑郁发病有关。
Objective: To detect the expression of neuronal growth-associated protein 43 (GAP43), postsynaptic density protein 95 (PSD95), and synaptophysin (SYN) in the prefrontal cortex of rats with comorbid epilepsy and depression, and to investigate the role of changes in the expression of synaptic-related proteins in the prefrontal cortex in the pathogenesis of comorbid epilepsy and depression. Methods: Adult female SD rats were selected for the experiment. The epilepsy model was established using the lithium-pilocarpine method, and the epileptic seizure grade was assessed using the Racine scoring standard. The depression model was established using the single-housed method combined with a Chronic Unpredictable Mild Stress (CUMS) paradigm. 14 days after epilepsy modeling, depression screening was performed, and the rats were divided into the comorbid epilepsy and depression group, the epilepsy-only group, the normal control group, and the depression-only group according to body weight measurement, sucrose solution preference rate, and open field test evaluation of depressive emotions. Immunohistochemical staining was used to detect the expression of GAP43, PSD95, and SYN proteins in the prefrontal cortex of each group of rats. Results: In terms of SYN expression, compared to the normal group, SYN expression was reduced in the other groups (P < 0.05); and compared to the epilepsy group, SYN expression was reduced in the depression and comorbid groups (P < 0.05). In terms of PSD95 expression, compared to the normal group, expression was reduced in the depression and comorbid groups (P < 0.05); and compared to the epilepsy group, PSD95 was reduced in the depression and comorbid groups (P < 0.05). GAP43 expression was highest in the normal group
| [1] | Chen, L., Xu, Y., Cheng, H., Li, Z., Lai, N., Li, M., et al. (2023) Adult-Born Neurons in Critical Period Maintain Hippocampal Seizures via Local Aberrant Excitatory Circuits. Signal Transduction and Targeted Therapy, 8, Article No. 225. https://doi.org/10.1038/s41392-023-01433-4 |
| [2] | Patel, D.C., Tewari, B.P., Chaunsali, L. and Sontheimer, H. (2019) Neuron-Glia Interactions in the Pathophysiology of Epilepsy. Nature Reviews Neuroscience, 20, 282-297. https://doi.org/10.1038/s41583-019-0126-4 |
| [3] | Jessberger, S. and Parent, J.M. (2015) Epilepsy and Adult Neurogenesis. Cold Spring Harbor Perspectives in Biology, 7, a020677. https://doi.org/10.1101/cshperspect.a020677 |
| [4] | Hanaya, R., Boehm, N. and Nehlig, A. (2007) Dissociation of the Immunoreactivity of Synaptophysin and GAP-43 during the Acute and Latent Phases of the Lithium-Pilocarpine Model in the Immature and Adult Rat. Experimental Neurology, 204, 720-732. https://doi.org/10.1016/j.expneurol.2007.01.002 |
| [5] | Zhang, Y., Cheng, X., Wu, L., Li, J., Liu, C., Wei, M., et al. (2023) Pharmacological Inhibition of S6K1 Rescues Synaptic Deficits and Attenuates Seizures and Depression in Chronic Epileptic Rats. CNS Neuroscience & Therapeutics, 30, e14475. https://doi.org/10.1111/cns.14475 |
| [6] | Keezer, M.R., Sisodiya, S.M. and Sander, J.W. (2016) Comorbidities of Epilepsy: Current Concepts and Future Perspectives. The Lancet Neurology, 15, 106-115. https://doi.org/10.1016/s1474-4422(15)00225-2 |
| [7] | Marques, K.L., Moreira, M.L., Thiele, M.C., Cunha-Rodrigues, M.C. and Barradas, P.C. (2023) Depressive-Like Behavior and Impaired Synaptic Plasticity in the Prefrontal Cortex as Later Consequences of Prenatal Hypoxic-Ischemic Insult in Rats. Behavioural Brain Research, 452, Article ID: 114571. https://doi.org/10.1016/j.bbr.2023.114571 |
| [8] | Lu, C., Gao, R., Zhang, Y., Jiang, N., Chen, Y., Sun, J., et al. (2021) S-Equol, a Metabolite of Dietary Soy Isoflavones, Alleviates Lipopolysaccharide-Induced Depressive-Like Behavior in Mice by Inhibiting Neuroinflammation and Enhancing Synaptic Plasticity. Food & Function, 12, 5770-5778. https://doi.org/10.1039/d1fo00547b |
| [9] | Nazir, F.H., Becker, B., Brinkmalm, A., Höglund, K., Sandelius, Å., Bergström, P., et al. (2018) Expression and Secretion of Synaptic Proteins during Stem Cell Differentiation to Cortical Neurons. Neurochemistry International, 121, 38-49. https://doi.org/10.1016/j.neuint.2018.10.014 |
| [10] | 邱红梅, 郭旺, 杨雪萍, 等. 癫痫伴抑郁模型大鼠海马突触相关蛋白的表达[J]. 中华行为医学与脑科学杂志, 2024, 33(1): 9-14. |
| [11] | 曹真真, 闫桂柳, 朱含笑, 等. 癫痫伴发抑郁大鼠杏仁核突触相关蛋白的表达[J]. 中风与神经疾病杂志, 2021, 38(12): 1088-1091. |
| [12] | Cohen, J.Y., Haesler, S., Vong, L., Lowell, B.B. and Uchida, N. (2012) Neuron-Type-Specific Signals for Reward and Punishment in the Ventral Tegmental Area. Nature, 482, 85-88. https://doi.org/10.1038/nature10754 |
| [13] | Nasrullah, N., Kerr, W.T., Stern, J.M., Wang, Y., Tatekawa, H., Lee, J.K., et al. (2023) Amygdala Subfield and Prefrontal Cortex Abnormalities in Patients with Functional Seizures. Epilepsy & Behavior, 145, Article ID: 109278. https://doi.org/10.1016/j.yebeh.2023.109278 |
| [14] | Truckenbrodt, S., Viplav, A., Jähne, S., Vogts, A., Denker, A., Wildhagen, H., et al. (2018) Newly Produced Synaptic Vesicle Proteins Are Preferentially Used in Synaptic Transmission. The EMBO Journal, 37, e98044. https://doi.org/10.15252/embj.201798044 |
| [15] | Chung, D., Shum, A. and Caraveo, G. (2020) GAP-43 and BASP1 in Axon Regeneration: Implications for the Treatment of Neurodegenerative Diseases. Frontiers in Cell and Developmental Biology, 8, Article 567537. https://doi.org/10.3389/fcell.2020.567537 |
| [16] | Ying, Z., Najm, I., Nemes, A., Pinheiro‐Martins, A.P., Alexopoulos, A., Gonzalez‐Martinez, J., et al. (2014) Growth‐associated Protein 43 and Progressive Epilepsy in Cortical Dysplasia. Annals of Clinical and Translational Neurology, 1, 453-461. https://doi.org/10.1002/acn3.69 |
| [17] | 韩丽君, 王志恒, 尚婷惠子, 等. β-细辛醚对抑郁模型大鼠海马神经突触可塑性功能因子GAP-43的影响[J]. 全科口腔医学电子杂志, 2019, 6(30): 140-141. |
| [18] | Duman, R.S. and Aghajanian, G.K. (2012) Synaptic Dysfunction in Depression: Potential Therapeutic Targets. Science, 338, 68-72. https://doi.org/10.1126/science.1222939 |
| [19] | Royero, P.X., Higa, G.S.V., Kostecki, D.S., dos Santos, B.A., Almeida, C., Andrade, K.A., et al. (2020) Ryanodine Receptors Drive Neuronal Loss and Regulate Synaptic Proteins during Epileptogenesis. Experimental Neurology, 327, Article ID: 113213. https://doi.org/10.1016/j.expneurol.2020.113213 |
| [20] | Ota, K.T., Liu, R., Voleti, B., Maldonado-Aviles, J.G., Duric, V., Iwata, M., et al. (2014) REDD1 Is Essential for Stress-Induced Synaptic Loss and Depressive Behavior. Nature Medicine, 20, 531-535. https://doi.org/10.1038/nm.3513 |
| [21] | Jia, C., Zhang, R., Wei, L., Xie, J., Zhou, S., Yin, W., et al. (2022) Investigation of the Mechanism of Tanshinone IIA to Improve Cognitive Function via Synaptic Plasticity in Epileptic Rats. Pharmaceutical Biology, 61, 100-110. https://doi.org/10.1080/13880209.2022.2157843 |
