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目的：探究不同时间内慢性不可预见性温和应激（CUMS）诱导的抑郁模型大鼠内侧前额叶皮层（mPFC）中大麻素受体CB1与AMPA受体亚基GluA1的变化。方法：将30只大鼠随机分为3组，3周模型组给予3周CUMS法造模，4周模型组给予4周CUMS造模，对照组不做任何处理。进行糖水偏爱、新颖抑制摄食和强迫游泳实验来检测各组大鼠行为学的变化，通过Western blot技术检测mPFC脑区突触体中CB1和GluA1蛋白表达。结果：与对照组相比，大鼠经历4周CUMS后糖水偏爱率降低、新颖抑制摄食测试中摄食潜伏期延长，强迫游泳测试中不动时间增加，而经历3周CUMS后大鼠行为学较对照组无明显差异，提示4周CUMS后抑郁大鼠造模成功。4周CUMS应激后可降低4周模型组mPFC脑区突触体中CB1及GluA1蛋白表达水平（P<0.05），而3周模型组CB1及GluA1表达水平和对照组无明显差异。结论：4周应激后制备抑郁动物模型大鼠最为稳定，慢性应激导致的抑郁与mPFC脑区中CB1和GluA1表达密切相关。
Abstract：Objective:To explore the changes of cannabinoid receptor(CB1)and AMPA receptor subunit GluA1 in the medial prefrontal cortex(mPFC)of depression model rats induced by chronic unpredictable mild stress(CUMS).Methods:A total of 30 rats were randomly divided into three groups. The three-week model group was given a three-week CUMS model,the four-week model group was given a four-week CUMS model,and the control group was given no treatment. The behaviors of rats were detected in each group,and the expression of CB1 and GluA1 protein in synaptosomes in mPFC brain region was detected by Western blot.Results:Compared with the control group,the surcose preference decreased,the feeding latency increased in the novel inhibition feeding test,and the immobility time increased in the forced swimming test in the four-week model group. However,after three weeks of CUMS,there was no obvious change in the behavior of rats compared with the control group,suggesting that four-week model of CUMS was successful. CUMS can reduce the expression level of CB1 and GluA1 protein in synaptosomes of mPFC brain area in four-week model group(P<0.05),but there was no significant difference between three-week model group and control group.Conclusion:Four-week CUMS was more likely to lead to depressive-like behavior in rats,which may be closely related to the expression of CB1 and GluA1 in mPFC.
1 Nemeroff CB. The state of our understanding of the pathophysiology and optimal treatment of depression:Glass half full or half empty?[J]. Am J Psychiatry,2020,177(8):671-685.
2 Huang Y,Wang Y,Wang H,et al. Prevalence of mental disorders in China:A cross-sectional epidemiological study[J]. Lancet Psychiatry,2019,6(3):211-224.
3 Malhi GS,Mann JJ. Depression[J]. Lancet,2018,392(10161):2299-2312.
4 Yin AQ,Wang F,Zhang X. Integrating endocannabinoid signaling in the regulation of anxiety and depression[J]. Acta Pharmacol Sin,2019,40(3):336-341.
5 Zhang J,Abdullah JM. The role of GluA1 in central nervous system disorders[J]. Rev Neurosci,2013,24(5):499-505.
6 Jiang B,Wang H,Wang JL,et al. Hippocampal salt-inducible kinase 2 plays a role in depression via the CREBregulated transcription coactivator 1-cAMP response element binding-brain-derived neurotrophic factor pathway[J]. Biol Psychiatry,2019,85(8):650-666.
7 张宇昕，盖聪，马浩洁，等.抑郁症大鼠内侧前额叶皮层PNNs表达及GABA能神经元功能改变[J].海南医学院学报，2021,27(4):241-245.
8 Yu Z,Chen N,Hu D,et al. Decreased density of perineuronal net in prelimbic cortex is linked to depressivelike behavior in young-aged rats[J]. Front Mol Neurosci,2020,13(4):1-12.
9 Han Y,Sun CY,Meng SQ,et al. Systemic immunization with altered myelin basic protein peptide produces sustained antidepressant-like effects[J]. Mol Psychiatry,2020,25(6):1260-1274.
10 Antoniuk S,Bijata M,Ponimaskin E,et al. Chronic unpredictable mild stress for modeling depression in rodents:Meta-analysis of model reliability[J]. Neurosci Biobehav Rev,2019,99(1):101-116.
11 Heshmati M,Christoffel DJ,Leclair K,et al. Depression and social defeat stress are associated with inhibitory synaptic changes in the nucleus accumbens[J]. J Neurosci,2020,40(32):6228-6233.
12 Ozcan H,Ayd?n N,Ayd?n MD,et al. Olfactory bulbectomy and raphe nucleus relationship:A new vision for well-known depression model[J]. Nord J Psychiatry,2020,74(3):194-200.
13 Geng J,Liu J,Yuan X,et al. Andrographolide triggers autophagy-mediated inflammation inhibition and attenuates chronic unpredictable mild stress(CUMS)-induced depressive-like behavior in mice[J]. Toxicol Appl Pharmacol,2019,379(1):114688.
14 Zhao YN,Cao YF,Zhang YH,et al. Nelumbo nucifera gaertn stems(Hegeng)improved depression behavior in CUMS mice by regulating NCAM and GAP-43 expression[J]. Evid Based Complement Alternat Med,2020,2020(1):3056954.
15 Wang S,Xu X,Ju X,et al. Melatonin ameliorated CUMS-induced depression-like behavior via restoring endoplasmic reticulum stress in rat hippocampus[J]. Neuroreport,2021,32(1):8-15.
16 Mao L,Lv FF,Yang WF,et al. Effects of Baihui electroacupuncture in a rat model of depression[J]. Ann Transl Med,2020,8(24):1646.
17 Yan W,Liu JF,Han Y,et al. Protein kinase Mzeta in medial prefrontal cortex mediates depressive-like behavior and antidepressant response[J]. Mol Psychiatry,2018,23(9):1878-1891.
18 Ma K,Zhang H,Wang S,et al. The molecular mechanism underlying GABAergic dysfunction in nucleus accumbens of depression-like behaviours in mice[J]. J Cell Mol Med,2019,23(10):7021-7028.
19 Drevets WC,Price JL,Furey ML. Brain structural and functional abnormalities in mood disorders:Implications for neurocircuitry models of depression[J]. Brain Struct Funct,2008,213(1-2):93-118.
20 Gerrits M,Westenbroek C,Fokkema DS,et al. Increased stress vulnerability after a prefrontal cortex lesion in female rats[J]. Brain Res Bull, 2003, 61(6):627-635.
21 Toyoda H. CB1 cannabinoid receptor-mediated plasticity of GABAergic synapses in the mouse insular cortex[J].Sci Rep,2020,10(1):7187.
22 Valverde O,Torrens M. CB1 receptor-deficient mice as a model for depression[J]. Neuroscience,2012,204(1):193-206.
23 Rana T,Behl T,Sehgal A,et al. Integrating endocannabinoid signalling in depression[J]. J Mol Neurosci,2021,71:2022-2034.
24 Ge Y,Wang YT. GluA1-homomeric AMPA receptor in synaptic plasticity and neurological diseases[J]. Neuropharmacology,2021:197(1):108708.
25 Qu W,Yuan B,Liu J,et al. Emerging role of AMPA receptor subunit GluA1 in synaptic plasticity:Implications for Alzheimer's disease[J]. Cell Prolif,2021,54(1):e12959.
26 Ballesta A,Alen F,Orio L,et al. Abrupt cessation of reboxetine along alcohol deprivation results in alcohol intake escalation after reinstatement of drinking[J]. Addict Biol,2021,26(3):e12957.
27 Rubino T,Prini P,Piscitelli F,et al. Adolescent exposure to THC in female rats disrupts developmental changes in the prefrontal cortex[J]. Neurobiol Dis,2015,73:60-69.
28 Good CH,Lupica CR. Afferent-specific AMPA receptor subunit composition and regulation of synaptic plasticity in midbrain dopamine neurons by abused drugs[J]. J Neurosci,2010,30(23):7900-7909.
基本信息:
DOI：10.13210/j.cnki.jhmu.20220325.001
中图分类号:R749.4
引用信息:
[1]张宇昕,孙红梅,盖聪,等.不同时长应激对大鼠抑郁样行为及内侧前额叶皮层CB1及GluA1表达的影响[J].海南医学院学报,2022,28(10):731-736.DOI:10.13210/j.cnki.jhmu.20220325.001.
基金信息:
国家自然科学青年基金项目（81803857）; 北京中医药大学新教师启动基金项目（2018-JYBZZ-XJSJJ002）~~
2022-03-28
2022-03-28
2022-03-28