噪声暴露下大鼠行为学和海马促肾上腺皮质激素释放因子蛋白表达的改变
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摘要
目的观察噪声暴露下大鼠行为学的改变,探讨噪声对生物体情绪行为和听力的负性影响及其可能的发生机制。方法选取行为学指标和ABR反应阈接近的健康大鼠24只,随机分为3组,每组8只。对照组(A组):正常喂养;噪声组(B组):每天固定时间噪声暴露4 h,持续28 d;氟西汀组(C组):噪声暴露的条件和时间与噪声组相同,每天噪声暴露后即腹腔注射剂量为10 mg/kg的氟西汀,持续28 d,噪声暴露前1 d、第7、14、28 d观察大鼠的旷场行为并检测ABR反应阈,实验前后记录大鼠的糖水偏爱百分比,最后断头取脑,剥离大鼠海马,Western-blot法测定各组大鼠海马CRF表达。结果第7、14、28 d,与对照组比较,其它组大鼠的旷场行为表现显著改变,差异有统计学意义(P<0.01);氟西汀组大鼠与噪声组比较,旷场行为差异均有统计学意义(P<0.01)。噪声暴露28d后,与对照组相较,噪声组和氟西汀组糖水偏爱百分比明显下降,差异有统计学意义(P<0.05);与噪声组比较,氟西汀组大鼠糖水偏爱明显增加,差异有统计学意义(P<0.05)。随着噪声暴露时间的延长,其ABR反应阈升高,差异有明显统计学意义(P<0.01)。氟西汀组海马CRF的表达较正常组增加,但较噪声组表达降低,各组间差异均有统计学意义(P<0.05)。结论长期的噪声暴露可使大鼠产生焦虑抑郁样行为,抗抑郁剂能改善这些行为的改变。海马CRF表达的增加可能参与噪声应激所致的大鼠行为学变化。
Objective To report behavioral features and investigate the role of corticotropin-releasing factor(CRF) in negative sentiment after chronic noise exposure in rats. Methods Twenty four male Wistar rats, selected based on similar behavioral indexes and ABR thresholds, were randomly divided into 3 groups(8 in each group) to be maintained normally(Group A), or exposed to intense noise for 4 hours a day at a fixed time for 28 days without(Group B) or with intraperitoneal injection of fluoxetine(10 mg/kg/day) after noise exposure(Group C). Animal behavior was recorded using an automatic tracking system and ABR thresholds recorded using a TDT system at 1 day before and 7,14 and 28 days after onset of experiment, followed by decapitation for collection of the hippocampus. Expression of CRF in the hippocampus was evaluated by Western blot. Results Behavioral features of rats in Groups B and C were significantly different compared with Group A(control)(P<0.01) and among themselves(P<0.01) at Days 7, 14 and 28.The saccharine preference index in the noise exposed groups was decreased as compared with the control group(P<0.05), although still higher in Group C than in Group B(P<0.05). ABR thresholds increased along with the duration of noise exposure. The level of CRF expression was elevated after noise exposure in Groups B and C(P<0.01), but lower in Group C than in Group B(P<0.01). Conclusion Long term exposure to noise can affect behavioral patterns in rats mimicking neurasthenia and depression, which can be improved by antidepressants. Increased expression of CRF in the hippocampus may play an important role in behavior changes in rats in response to noise induced stress.
Objective To report behavioral features and investigate the role of corticotropin-releasing factor(CRF) in negative sentiment after chronic noise exposure in rats. Methods Twenty four male Wistar rats, selected based on similar behavioral indexes and ABR thresholds, were randomly divided into 3 groups(8 in each group) to be maintained normally(Group A), or exposed to intense noise for 4 hours a day at a fixed time for 28 days without(Group B) or with intraperitoneal injection of fluoxetine(10 mg/kg/day) after noise exposure(Group C). Animal behavior was recorded using an automatic tracking system and ABR thresholds recorded using a TDT system at 1 day before and 7,14 and 28 days after onset of experiment, followed by decapitation for collection of the hippocampus. Expression of CRF in the hippocampus was evaluated by Western blot. Results Behavioral features of rats in Groups B and C were significantly different compared with Group A(control)(P<0.01) and among themselves(P<0.01) at Days 7, 14 and 28.The saccharine preference index in the noise exposed groups was decreased as compared with the control group(P<0.05), although still higher in Group C than in Group B(P<0.05). ABR thresholds increased along with the duration of noise exposure. The level of CRF expression was elevated after noise exposure in Groups B and C(P<0.01), but lower in Group C than in Group B(P<0.01). Conclusion Long term exposure to noise can affect behavioral patterns in rats mimicking neurasthenia and depression, which can be improved by antidepressants. Increased expression of CRF in the hippocampus may play an important role in behavior changes in rats in response to noise induced stress.
引文
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12 Dautzenberg FM,Hauger RL.The CRF peptide family and their receptors:yet more partners discovered[J].Trends in Pharmacological Science,2002,23(2):71-77.
13 Arborelius L,Owens MJ,Plotsky PM,et al.The role of corticotrophin releasing factor in depress and anxiety disorder[J].J Endocrinol,1999,160(2):1-12.
14 Valentino RJ,Lucki I.Corticotropin-releasing ractor in the dorsal raphe nucleus:linking stress coping and addiction.[J].BrainRes.2010,16;1314:29-37
15杨红菊,李云峰,赵楠,等.抗抑郁剂对慢性应激大鼠脑内促肾上腺皮质激素释放因子CRFmRNA表达的影响[J].中国神经免疫学和神经病学杂志,2002,9(4):52-54.Yang HJ,Li YF,Zhao N,et al.The Effect of antidepressants on the corti cotropin-releasing factor mRNA expression in the brain of rats following chronic stress[J].Chinese Journal of Neuroimmunol and Neurol,2002,9(4):52-54
16刘昊,赵艳霞,张蕊,等.应激大鼠下丘脑5-羟色胺1A受体活性与促肾上腺皮质激素释放因子表达的关系[J].解剖学杂志,2011,34:339-341.Liu H,Zhao YX,Zhang R,et al.Relationship between activity of 5一HTlA receptor and expression of corti cotropin-releasing factor in hypothalthalamus in stress rats[J].Chinese Journal of Anatomy,2011,34:339-341.
17贾若,孙凤新,刘博.耳鸣和情绪认知的相关性研究[J].中华耳科学杂志,2016,14(2):158-162.Jia R,Sun FX,Liu B.Effects of cognition and emotion changes on tinnitus[J],Chinese Journal of Otology 2016,14(2):158-162.
18苏丹,张璞,王彦茹,等.耳鸣习服疗法[J].中华耳科学杂志,2017,15(4):498-501.Su D,Zhang P,Wang YR,et al.Tinnitus retraining therapy[J].Chinese Journal of Otology,2017,15(4):498-501.
19宋凡,陈秀兰,王斌,等.急、慢性耳鸣的临床和心理声学特征分析[J].中华耳科学杂志,2017,15(1):71-76.Song F,Chen XL,Wang BC,et al.Clinical and psychoacoustic characteristics in patients with acute and chronic tinnitus[J].Chinese Journal of Otology2017,15(1):71-76.
20解为全,廖华,杨希林,等.水杨酸钠致耳鸣大鼠脑海马区促肾上腺皮质激素释放因子的表达[J].听力学及言语疾病杂志,2013,21(2):167-170.Xie WQ,Liao H,Yang XL,et al.Expression of corticotropin-releasing factor in rat’s hippocampus involves in the pathology of salicylate induced tinnitus[J].Journal of Audiology and Speech Pathology,2013,21(2):167-170.
21陈抗松,廖华,杨希林,等.水杨酸致耳鸣大鼠的行为学及听性脑干反应改变[J].听力学及言语疾病杂志,2013,21(2):163-166.Chen KS,Liao H,Yang XL,et al.Chanegs of the behavior and ABR on the tinnitus rat model induced by salicylate[J].Journal of Audiology and Speech Pathology,2013,21(2):163-166.
22陈抗松,廖华,杨希林,等.慢性不可预见性温和刺激大鼠模型的听性脑干反应的改变[J].中华耳科学杂志,2013,11(2),241-244.Chen KS,Liao H,Yang XL,et al.Changes of the behavior andABRon CUMS rat model[J].Chinese Journal of Otology,2013,11(2):241-244.
2 Wibke S,Annalisa Z,Mirko J,et al.Noise-induced inner hair cell ribbon loss disturbs central arc mobilization:a novel molecular paradigm for understanding tinnitus[J].Mol Neurobiol,2013,47(1):261-279.
3 Yang C,Wang G,Wang H,et al.Cytoskeletal alterations in rat hippocampus following chronic unpredictable mild stress and re-exposure to acute and chronic unpredictable mild stress[J].Behav Brain Res,2009,205(2):518-524.
4 Willner P.Chronic mild stress(CMS)revisited:consistency and behavi-neurobiologicalaural concordance ineffects of CMS[J].Neuropsychobiology,2005,52(2):90-110.
5 Sundaramahalingam Manikandan,Moorthy K Padma,Ramasundaram Srikumar,et al.Effects of chronic noise sress on spatial memory of rats in relation to neuronal dendritic alteration and free radical-imbalance in hippocampus and medial prefrontal cortex[J].Neuroscience Letters,2006,399(1-2):17-22.
6 Samson J,Sheeladevi R,Ravindran R,Senthilvelan M.Stress response in rat brain after different durations of noise exposure.Neurosci Res.2007;57(1):143-147.
7 Stansfeld SA,Berglund B,Clark C,et al.Aircraft and road traffic noise and children’s cognition and health:a cross national study.Lancet.2005;365(9475):1942-1949.
8 Cui B,Wu M,She X.Effects of chronic noise exposure on spatial learning and memory of rats in relation to neurotransmitters and NMDAR2B alterations in the hippocampus[J].J Occup Health,2009,51(2):152-158.
9 Fizza NA,Saida HA,Zehra BA,et al.Sub-chronic exposure to noise affects locomotor activity and produces anxiogenic and depressive like behavior in rats[J].Pharmacological Reports,2012,64(1):64-69.
10 Ye Y,Wang G,Wang H,et al.Brain-derived neurotrophic factor(BDNF)infusionrestored astrocytic plasticity in the hippocampus of a rat model of depression[J].Neurosci Lett.2011,503(1):15-19.
11 Saida HA,Fizza NA,Zehra BA,et al.Decreased hippocampal5-HT and DA levels following sub-chronic exposure to noise stress:impairment in both spatial and recognition memory in male rats[J].Sci Pharm,2012,80(4):1001-1011.
12 Dautzenberg FM,Hauger RL.The CRF peptide family and their receptors:yet more partners discovered[J].Trends in Pharmacological Science,2002,23(2):71-77.
13 Arborelius L,Owens MJ,Plotsky PM,et al.The role of corticotrophin releasing factor in depress and anxiety disorder[J].J Endocrinol,1999,160(2):1-12.
14 Valentino RJ,Lucki I.Corticotropin-releasing ractor in the dorsal raphe nucleus:linking stress coping and addiction.[J].BrainRes.2010,16;1314:29-37
15杨红菊,李云峰,赵楠,等.抗抑郁剂对慢性应激大鼠脑内促肾上腺皮质激素释放因子CRFmRNA表达的影响[J].中国神经免疫学和神经病学杂志,2002,9(4):52-54.Yang HJ,Li YF,Zhao N,et al.The Effect of antidepressants on the corti cotropin-releasing factor mRNA expression in the brain of rats following chronic stress[J].Chinese Journal of Neuroimmunol and Neurol,2002,9(4):52-54
16刘昊,赵艳霞,张蕊,等.应激大鼠下丘脑5-羟色胺1A受体活性与促肾上腺皮质激素释放因子表达的关系[J].解剖学杂志,2011,34:339-341.Liu H,Zhao YX,Zhang R,et al.Relationship between activity of 5一HTlA receptor and expression of corti cotropin-releasing factor in hypothalthalamus in stress rats[J].Chinese Journal of Anatomy,2011,34:339-341.
17贾若,孙凤新,刘博.耳鸣和情绪认知的相关性研究[J].中华耳科学杂志,2016,14(2):158-162.Jia R,Sun FX,Liu B.Effects of cognition and emotion changes on tinnitus[J],Chinese Journal of Otology 2016,14(2):158-162.
18苏丹,张璞,王彦茹,等.耳鸣习服疗法[J].中华耳科学杂志,2017,15(4):498-501.Su D,Zhang P,Wang YR,et al.Tinnitus retraining therapy[J].Chinese Journal of Otology,2017,15(4):498-501.
19宋凡,陈秀兰,王斌,等.急、慢性耳鸣的临床和心理声学特征分析[J].中华耳科学杂志,2017,15(1):71-76.Song F,Chen XL,Wang BC,et al.Clinical and psychoacoustic characteristics in patients with acute and chronic tinnitus[J].Chinese Journal of Otology2017,15(1):71-76.
20解为全,廖华,杨希林,等.水杨酸钠致耳鸣大鼠脑海马区促肾上腺皮质激素释放因子的表达[J].听力学及言语疾病杂志,2013,21(2):167-170.Xie WQ,Liao H,Yang XL,et al.Expression of corticotropin-releasing factor in rat’s hippocampus involves in the pathology of salicylate induced tinnitus[J].Journal of Audiology and Speech Pathology,2013,21(2):167-170.
21陈抗松,廖华,杨希林,等.水杨酸致耳鸣大鼠的行为学及听性脑干反应改变[J].听力学及言语疾病杂志,2013,21(2):163-166.Chen KS,Liao H,Yang XL,et al.Chanegs of the behavior and ABR on the tinnitus rat model induced by salicylate[J].Journal of Audiology and Speech Pathology,2013,21(2):163-166.
22陈抗松,廖华,杨希林,等.慢性不可预见性温和刺激大鼠模型的听性脑干反应的改变[J].中华耳科学杂志,2013,11(2),241-244.Chen KS,Liao H,Yang XL,et al.Changes of the behavior andABRon CUMS rat model[J].Chinese Journal of Otology,2013,11(2):241-244.