陈霄,尹露,安云,等.含音乐的丰富环境对慢性温和不可预知应激大鼠抑郁样行为及其海马神经可塑性的影响[J].中华物理医学与康复杂志,2024,46(12):1065-1071
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含音乐的丰富环境对慢性温和不可预知应激大鼠抑郁样行为及其海马神经可塑性的影响 |
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DOI:10.3760/cma.j.cn421666-20230131-00074 |
中文关键词: 抑郁症 CUMS模型 丰富环境 音乐 神经可塑性 海马 |
英文关键词: Depression Stress Environmental enrichment Music Neural plasticity Hippocampus |
基金项目:SMC中国传统康复医学研究项目(SMC2013);上海市卫生健康系统重点扶持学科-康复医学(2023ZDFC0301) |
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中文摘要: |
目的 观察含音乐的丰富环境对慢性温和不可预知应激(CUMS)模型大鼠抑郁样行为及其神经可塑性相关蛋白的蛋白激酶 A(PKA)、环磷腺苷效应元件结合蛋白(CREB)、磷酸化CREB 蛋白(p-CREB)、脑源性神经营养因子(BDNF)表达的影响。 方法 选取雄性SD大鼠40只,按照随机数字表法将其分为空白组、模型对照组、无音乐丰富环境组和含音乐丰富环境组,每组大鼠10只。模型对照组、无音乐丰富环境组和含音乐丰富环境组进行CUMS造模。造模成功后,空白组和模型对照组均于常规鼠笼中接受常规饲养21 d,无音乐丰富环境组则给予丰富环境干预21 d,含音乐丰富环境组在普通丰富环境中增加音乐治疗。4组大鼠均于干预21 d后分别进行糖水偏爱实验、旷场实验和强迫游泳实验。行为学检测结束后,4组大鼠断头取脑,采用免疫组化法和免疫蛋白印迹法分别检测其海马区PKA、CREB、p-CREB、BDNF蛋白的表达。 结果 干预21 d后,模型对照组大鼠的糖水偏爱率、旷场内活动总距离、中心区活动距离、站立次数和游泳不动时间与空白组比较,差异均有统计学意义(P<0.05);无音乐丰富环境组的糖水偏爱率、旷场内活动总距离、中心区活动距离和游泳不动时间与模型对照组比较,差异均有统计学意义(P<0.05);含音乐丰富环境组的糖水偏爱率、旷场内活动总距离、站立次数和游泳不动时间与模型对照组比较,差异均有统计学意义(P<0.05);无音乐丰富环境组的游泳不动时间为(110.94 s±37.56 s),与含音乐丰富环境组的(66.78 s±46.47 s)比较,差异有统计学意义(P<0.05)。干预21 d后,模型对照组大鼠海马区CREB、p-CREB、BDNF蛋白的阳性面积百分比较空白组均显著下降(P<0.05);无音乐丰富环境组和含音乐丰富环境组的CREB、p-CREB、BDNF蛋白的阳性面积百分比与模型对照组比较,差异均有统计学意义(P<0.05),且以含音乐丰富环境组更为显著,与无音乐丰富环境组比较,差异有统计学意义(P<0.05)。干预21 d后,模型对照组大鼠海马区PKA、CREB、p-CREB、BDNF的蛋白表达水平与空白组比较,差异均有统计学意义(P<0.05);无音乐丰富环境组PKA、CREB、p-CREB的蛋白表达水平较模型对照组均明显升高(P<0.05);含音乐丰富环境组PKA、CREB、p-CREB、BDNF蛋白表达水平较模型对照组和无音乐丰富环境组,均显著升高(P<0.05)。 结论 丰富环境可显著改善大鼠的抑郁样行为,而在丰富环境中增加音乐可提高其抗抑郁的疗效,且丰富环境的抗抑郁机制可能与其可上调PKA、CREB、p-CREB、BDNF蛋白表达水平有关。 |
英文摘要: |
Objective To observe any effect of environmental enrichment on depressive behavior and the expression of the neuroplasticity-related protein kinase A (PKA), cAMP response element binding protein (CREB), phosphorylated CREB (p-CREB), and brain-derived neurotrophic factor (BDNF) in rats subjected to chronic, unpredictable mild stress (CUMS). Methods Forty male Sprague-Dawley rats were divided at random into a blank group, a model control group, a no-music-environmental enrichment (NMEE) group and a music-environmental enrichment (MEE) group, each of 10. CUMS was induced in all except the blank group. After successful modeling, the rats in the blank and model control groups were housed in conventional cages for 21 days, while the MEE group received 21 days of environmental enrichment with music and the NMEE group was similarly housed without the music. After the intervention, all groups underwent a sugar water preference experiment, an open field experiment, and a forced swimming experiment. They were then sacrificed and hippocampal PKA, CREB, p-CREB and BDNF protein expressions were detected using immunohistochemistry and western blotting. Results After the intervention there were significant differences between the model control and blank groups in their sugar water preference, the total distance of their open field activities, the central area distance of their activities, their time spent standing up, and the duration of immobility during swimming. Those indicators were also significantly different between the MEE and model control groups. The average duration of swimming immobility of the NMEE group was significantly longer than the MEE group′s average. The percentage the hippocampus positive for CREB, p-CREB or BDNF protein had decreased significantly in the model control group compared to the blank group, while those percentages in the NMEE and especially the MEE group were significantly different from those of the model control group. PKA, CREB, p-CREB and BDNF protein expression in the model control group was significantly different from that in the blank group, while those levels in the NMEE group were significantly higher than in the model control group on average. The levels in the MEE group were the highest of all. Conclusions Environmental enrichment can significantly improve depressive behavior resulting from CUMS, at least in rats. Adding music to an enriched environment can enhance its anti-depressant efficacy. The anti-depressant mechanism of environmental enrichment may be related to its upregulation of PKA, CREB, p-CREB and BDNF protein expression. |
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