癫痫伴发抑郁大鼠额前皮质脑源性神经营养因子及其受体的表达研究
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摘要
目的观察癫痫伴发抑郁(epilepsy-associated depression,EAD)大鼠额前皮质脑源性神经营养因子(brain-derived neurotrophic fctor,BDNF)及其高亲和力受体原肌球蛋白受体激酶B(tropomyosin receptor kinase B,Trk B)的表达情况。方法 52只雌性SD大鼠随机分为正常组、抑郁组(采用慢性不可预见中等应激刺激结合孤养法建立大鼠慢性应激抑郁模型)、癫痫组和EAD组,每组13只,后2组利用氯化锂-匹罗卡品建立癫痫模型,于造模后第14天对癫痫模型进行抑郁筛选,每只大鼠以抑郁各指标评分分别入癫痫组和EAD组。于造模成功后第4周分别用免疫荧光染色检测额前皮质BDNF及Trk B免疫阳性细胞表达;用Western blot检测额前皮质BDNF及Trk B蛋白定量表达。结果与癫痫组比较,EAD组额前皮质BDNF和Trk B阳性细胞数减少[(26. 08±1. 18)个/视野vs (32. 86±2. 28)个/视野,P <0. 05;(26. 48±4. 66)个/视野vs (35. 86±4. 37)个/视野,P <0. 05]。与正常组和癫痫组比较,EAD组额前皮质BDNF和Trk B蛋白表达明显减少(0. 522±0. 028 vs 0. 912±0. 035和1. 248±0. 066,P <0. 05;0. 494±0. 015 vs 0. 663±0. 024和1. 035±0. 048,P <0. 05)。结论 EAD大鼠额前皮质BDNF、Trk B蛋白的表达减少可能与EAD发病有关。
Objective To study the expressions of brain-derived neurotrophic factor( BDNF) and its high-affinity tropomyosin receptor kinase B( TrkB) protien in prefrontal cortex of rats with epilepsy-associated depression( EAD). Methods Fifty-two rats were randomly divided into control group,depression group,epilepsy group,and EAD group( 13 in each group). EAD rats were screened on day 14 after an epilepsy model was induced by lithium chloride-pilocarpine. Expressioons of BDNF and TrkB protien in prefrontal cortex of rats were detected by Weatern blot with immunofluorescence staining at week 4 after the epilepsy model was established. Results The number of BNDF and TrkB positive cells was smaller in EAD group than in epilepsy group( 26. 08 ± 1. 18/per visual field vs 32. 86 ± 2. 28/per visual field,P <0. 05; 26. 48 ± 4. 66/per visual field vs 35. 86 ± 4. 37/per visual field,P < 0. 05). The expression levels of BDNF and Trk B protein were significantly lower in EAD group than in control group and epilepsy group( 0. 522 ± 0. 028 vs 0. 912 ± 0. 035 and 1. 248 ± 0. 066,P < 0. 05; 0. 494 ± 0. 015 vs 0. 663 ± 0. 024 and1. 035 ± 0. 048,P < 0. 05). Conclusion Down-regulated expressions of BDNF and Trk B protein in prefrontal cortex of rats are related with the occurrence of EAD.
Objective To study the expressions of brain-derived neurotrophic factor( BDNF) and its high-affinity tropomyosin receptor kinase B( TrkB) protien in prefrontal cortex of rats with epilepsy-associated depression( EAD). Methods Fifty-two rats were randomly divided into control group,depression group,epilepsy group,and EAD group( 13 in each group). EAD rats were screened on day 14 after an epilepsy model was induced by lithium chloride-pilocarpine. Expressioons of BDNF and TrkB protien in prefrontal cortex of rats were detected by Weatern blot with immunofluorescence staining at week 4 after the epilepsy model was established. Results The number of BNDF and TrkB positive cells was smaller in EAD group than in epilepsy group( 26. 08 ± 1. 18/per visual field vs 32. 86 ± 2. 28/per visual field,P <0. 05; 26. 48 ± 4. 66/per visual field vs 35. 86 ± 4. 37/per visual field,P < 0. 05). The expression levels of BDNF and Trk B protein were significantly lower in EAD group than in control group and epilepsy group( 0. 522 ± 0. 028 vs 0. 912 ± 0. 035 and 1. 248 ± 0. 066,P < 0. 05; 0. 494 ± 0. 015 vs 0. 663 ± 0. 024 and1. 035 ± 0. 048,P < 0. 05). Conclusion Down-regulated expressions of BDNF and Trk B protein in prefrontal cortex of rats are related with the occurrence of EAD.
引文
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[3] Li Y,Yan J,Zhu X,et al. Dilated Virchow-Robin spaces in the hippocampus impact behaviors and effects of anti-depressant treatment in model of depressed rats[J]. J Affect Disord,2017,219:17-24. DOI:10. 1016/j. jad. 2017. 04. 035.
[4] Mazarati AM,Pineda E,Shin D,et al. Comorbidity between epilepsy and depression:role of hippocampal interleukin-1beta[J].Neurobiol Dis,2010,37(2):461-467. DOI:10. 1016/j. nbd.2009. 11. 001.
[5]卢颖瑜,秦兴华,黄秉文.成人症状性癫痫患者生活质量及自我效能评价分析[J].中国医学创新,2015,12(32):8-11.DOI:1. 3969/j. issn. 1674-4985. 2015. 32. 003.
[6] Rayner G,Jackson GD,Wilson SJ. Behavioral profiles in frontal lobe epilepsy:autobiographic memory versus mood impairment[J]. Epilepsia,2015,56(2):225-233. DOI:10. 1111/epi.12902.
[7] Briz V,Zhu G,Wang Y,et al. Activity-dependent rapid local Rho A synthesis is required for hippocampal synaptic plasticity[J]. J Neurosci,2015,35(5):2269-2282. DOI:10. 1523/JNEUROSCI. 2302-14. 2015.
[8] Pedrotti Moreira F,Borges CJ,Wiener CD,et al. Serum brain-derived neurotrophic factor levels in subjects with major depressive disorder with previous suicide attempt:a population based study[J]. Psychiatry Res,2018,262:500-504. DOI:l0. 1016/j. psychres. 2017. 09. 033.
[9] Grech AM,Ratnayake U,Hannan AJ,et al. Sex-dependent effects of environmental enrichment on spatial memory and brain-derived neurotrophic factor(BDNF)signaling in a developmental “twohit”mouse model combining BDNF haploinsufficiency and chronic glucocorticoid stimulation[J]. Front Behav Neurosci,2018,12:227. DOI:10. 3389/fnbeh. 2018. 00227.
[10] Zhu C,Xu J,Lin Y,et al. Loss of microglia and impaired brainneurotrophic factor signaling pathway in a comorbid model of chronic pain and depression[J]. Front Psychiatry,2018,9:442.DOI:10. 3389/fpsyt. 2018. 00442.
[11] Phitltps C. Brain-derived neurotrophic factor,depression,andphysical actitity:making the neuroplastic connection[J]. Neural Hast,2017,2017:7260130. DOI:10. 1155/2017/7260130.
[12] Santos AR,Mele M,Vaz SH,et al. Differential role of the proteasome in the early and late phases of BDNF-induced facilitation of LTP[J]. J Neurosci,2015,35(8):3319-3329. DOI:10. 1523/JNEUROSCI. 4521-14. 2015.
[13] Zhang JC,Wu J,Fujita Y,et al. Antidepressant effects of TrkB ligands on depression-like behavior and dendritic changes in mice after inflammation[J]. Int J Neuropsychopharmacol,2014,18(4):1-12. DOI:10. 1093/ijnp/pyu077.
[14] Yin Y,Hou Z,Wang X,et al. The BDNF Val66Met polymorphism,resting-state hippocampal functional connectivity and cognitive deficits in acute late-onset depression[J]. J Affect Disord,2015,183:22-30. DOI:10. 1016/j. jad. 2015. 04. 050.
[15] Nakazawa T,Hashimoto R,Sakoori K,et al. Emerging roles of ARHGAP33 in intracellular trafficking of TrkB and pathophysiology of neuropsychiatric disorders[J]. Nat Commun,2016,7:10594. DOI:10. 1038/ncomms10594.
[16]徐连萍,李承玉,王群.脑源性神经营养因子基因单核苷酸多态性位点G196A、C270T与癫痫的相关性研究[J].癫痫杂志,2018,4(2):98-105. DOI:10. 7507/2096-0247. 20180021.
[17] Chowdhury AA,Gawali NB,Shinde P,et al. Imperetorin ameliorates lipopolysaccharide induced memory deficit by mitagating proinflammatory cytokines,oxidates stress and modulating brain-derived neurotropic factor[J]. Cytokine,2018,110:78-86.DOI:10. 1016/j/cyto. 2018. 04. 018.
[18] Falcicchia C,Paolone G,Emerich DF,et al. Seizure-suppressant and neuroprotective effects of encapsulated BDNF-producing cells in a rat model of temporal lobe epilepsy[J]. Mol Ther Methods Clin Dev,2018,9:211-224. DOI:10. 1016/j. omtm. 2018. 03.001.
[19] Jin M,Sheng W,Han L,et al. Activation of BDNF-TrkB signaling pathway-regulated brain inflammation in pentylenetetrazole-induced seizures in zebrafish[J]. Fish Shellfish Immunol,2018,83:26-36. DOI:10. 1016/j. fsi. 2018. 09. 010.
[20] Torres CM,Siebert M,Bock H,et al. Tyrosine receptor kinase B gene variants(NTRK2 variants)are associated with depressive disorders in temporal lobe epilepsy[J]. Epilepsy Behav,2017,71(Pt A):65-72. DOI:10. 1016/j. yebeh. 2017. 03. 030.