跑步对CUS抑郁模型小鼠内侧前额叶皮质内PV<sup>+</sup>中间神经元的影响

秦露; 唐静; 梁芯; 綦英强; 罗艳敏; 肖倩; 黄杜娟; 周梅; 周宇宁; 唐勇

doi:10.16016/j.2097-0927.202208205

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跑步对CUS抑郁模型小鼠内侧前额叶皮质内PV⁺中间神经元的影响

基础医学 | 更新时间：2026-01-09

- 跑步对CUS抑郁模型小鼠内侧前额叶皮质内PV⁺中间神经元的影响
- Running exercise shows anti-depressive effect in mice through PV⁺ interneurons in medial prefrontal cortex
- 陆军军医大学学报 2023年45卷第3期页码：209-218
- 作者机构：
  
  1.400016 重庆，重庆医科大学基础医学院组织与胚胎学教研室
  2.400016 重庆，重庆医科大学基础医学院病理生理学教研室
  3.400016 重庆，重庆医科大学生命科学研究院
  4.400016 重庆，重庆医科大学基础医学院生理学教研室
  5.400016 重庆，重庆医科大学基础医学院放射医学教研室
- 作者简介：
  
  [ 唐勇，E-mail：ytang062@163.com TANG Yong, E-mail: ytang062@163.com
- 基金信息：
  
  国家自然科学基金面上项目(82171522);国家自然科学基金青年科学基金(82001436)
- DOI：10.16016/j.2097-0927.202208205
  中图分类号： R322.81;R455;R749.4
- 收稿：2022-08-29，
  
  修回：2022-11-04，
  
  纸质出版：2023-02-15
- 稿件说明：
移动端阅览
秦露, 唐静, 梁芯, 等. 跑步对CUS抑郁模型小鼠内侧前额叶皮质内PV⁺中间神经元的影响[J]. 陆军军医大学学报, 2023,45(3):209-218.

Lu QIN, Jing TANG, Xin LIANG, et al. Running exercise shows anti-depressive effect in mice through PV⁺ interneurons in medial prefrontal cortex[J]. Journal of Army Medical University, 2023, 45(3): 209-218.
秦露, 唐静, 梁芯, 等. 跑步对CUS抑郁模型小鼠内侧前额叶皮质内PV⁺中间神经元的影响[J]. 陆军军医大学学报, 2023,45(3):209-218. DOI： 10.16016/j.2097-0927.202208205.

Lu QIN, Jing TANG, Xin LIANG, et al. Running exercise shows anti-depressive effect in mice through PV⁺ interneurons in medial prefrontal cortex[J]. Journal of Army Medical University, 2023, 45(3): 209-218. DOI： 10.16016/j.2097-0927.202208205.

摘要

目的

探讨跑步对慢性不可预知性(chronic unpredictable stress，CUS)抑郁症模型小鼠抑郁样行为的影响和内侧前额叶皮质(medial prefrontal cortex，mPFC)内GABA能中间神经元、PV

中间神经元和GAD67

/PV

细胞比例的影响。

方法

选取4~6周龄的雄性C57BL/6小鼠，CUS建模成功后，利用糖水偏好实验结果将其以分层随机法分为对照组、CUS模型对照组和CUS模型+跑步组。运用糖水偏好实验、强迫游泳实验和悬尾实

验评估各组小鼠的行为学水平。采用qRT-PCR检测小鼠mPFC中GAD1、GAD2、PV和CCK的mRNA表达水平。采用免疫组织化学和现代体视学相结合的方法对小鼠mPFC内GABA能中间神经元和PV

中间神经元数量进行精确三维定量，并分析PV

/GAD67

细胞比例。

结果

与CUS模型对照组小鼠相比，CUS模型+跑步组小鼠和对照组的糖水偏好百分比显著增加(

0.05)，强迫游泳不动时间显著降低(

0.05)，悬尾不动时间显著降低(

0.05)；对照组、CUS模型对照组和CUS模型+跑步组小鼠mPFC内GAD1、GAD2和CCK的mRNA表达水平以及GABA能中间神经元数量差异无统计学意义(

0.05)；CUS模型对照组小鼠mPFC中PV的mRNA表达水平、PV

中间神经元数量和PV

/GAD67

细胞比例均显著低于CUS模型+跑步组和对照组(

0.05)。

结论

跑步可能通过调节PV

中间神经元的数量和基因表达从而发挥抗抑郁效应。

Abstract

Objective

To investigate the effect of running exercise on depression-like behaviors in chronic unpredictable stress (CUS)-induced depression mice and GABAergic interneurons

interneurons and ratio of GAD67

/PV

cells in medial prefrontal cortex (mPFC).

Methods

After mouse model of depression was successfully established through CUS

these male C57BL/6 mice aged 4~6 weeks were randomly divided into control group

CUS control group and CUS+running group according to the results of sucrose preference test. The behaviors of the 3 groups were evaluated with sucrose preference test

forced swimming test and tail suspension test. The mRNA expression levels of GAD1

GAD2

PV and CCK in mPFC of mice were detected using qRT-PCR. The number of GABAergic interneurons and PV

interneurons in mPFC of mice were quantified using immunohistochemical assay and unbiased stereological technique

and the ratio of PV

/GAD67

cells was calculated.

Results

Compared with those in CUS control group

the mice from the CUS+running and control groups showed a significantly higher percentage of sucrose preference (

0.05)

orter forced swimming immobility time (

0.05)

and decreased tail suspension immobility time (

0.05). There were no obvious differences in mRNA expression levels of GAD1

GAD2 and CCK and number of GABAergic interneurons in mPFC in the 3 groups (P

0.05). The mRNA level of PV

number of PV

interneurons and ratio of PV

/GAD67

cells in mPFC were remarkably lower in the CUS group than the CUS +running group and control group (

0.05).

Conclusion

Running exercise may exert anti-depressive effects through regulating the number and gene expression of PV

interneurons.

关键词

Keywords

references

MCCARRON R M, SHAPIRO B, RAWLES J, et al . Depression[J ] . Ann Intern Med, 2021, 174(5): AITC202105180. DOI:10.7326/aitc202105180.

SCHMITTER M, SPIJKER J, SMIT F, et al . Exercise enhances: study protocol of a randomized controlled trial on aerobic exercise as depression treatment augmentation[J ] . BMC Psychiatry, 2020, 20(1): 585. DOI:10.1186/s12888-020-02989-z.

TANG J, LIANG X, DOU X Y, et al . Exercise rather than fluoxetine promotes oligodendrocyte differentiation and myelination in the hippocampus in a male mouse model of depression[J ] . Transl Psychiatry, 2021, 11(1): 622. DOI:10.1038/s41398-021-01747-3.

HOWARD D M, ADAMS M J, CLARKE T K, et al . Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions[J ] . Nat Neurosci, 2019, 22(3): 343-352. DOI:10.1038/s41593-018-0326-7.

MARKRAM H, TOLEDO-RODRIGUEZ M, WANG Y, et al . Interneurons of the neocortical inhibitory system[J ] . Nat Rev Neurosci, 2004, 5(10): 793-807. DOI:10.1038/nrn1519.

BANASR M, LEPACK A, FEE C, et al . Characterization of GABAergic marker expression in the chronic unpredictable stress model of depression[J ] . Chronic Stress, 2017, 1: 247054701772045. DOI:10.1177/2470547017720459.

POCHWAT B, NOWAK G, SZEWCZYK B. Brain glutamic acid decarboxylase-67kDa alterations induced by magnesium treatment in olfactory bulbectomy and chronic mild stress models in rats[J]. Pharmacol Rep, 2016, 68(5): 881-885. DOI:10.1016/j.pharep.2016.04.011.

TAI F, WANG C, DENG X, et al . Treadmill exercise ameliorates chronic REM sleep deprivation-induced anxiety-like behavior and cognitive impairment in C57BL/6J mice[J ] . Brain Res Bull, 2020, 164: 198-207. DOI:10.1016/j.brainresbull.2020.08.025.

COXON J P, CASH R F H, HENDRIKSE J J, et al . GABA concentration in sensorimotor cortex following high-intensity exercise and relationship to lactate levels[J ] . J Physiol, 2018, 596(4): 691-702. DOI:10.1113/JP274660.

WHISSELL P D, CAJANDING J D, FOGEL N, et al . Comparative density of CCK- and PV-GABA cells within the cortex and hippocampus[J ] . Front Neuroanat, 2015, 9: 124. DOI:10.3389/fnana.2015.00124.

DELEUZE C, BHUMBRA G S, PAZIENTI A, et al . Strong preference for autaptic self-connectivity of neocortical PV interneurons facilitates their tuning to γ-oscillations[J ] . PLoS Biol, 2019, 17(9): e3000419. DOI:10.1371/journal.pbio.3000419.

CZÉH B, VARDYA I, VARGA Z, et al . Long-term stress disrupts the structural and functional integrity of GABAergic neuronal networks in the medial prefrontal cortex of rats[J ] . Front Cell Neurosci, 2018, 12: 148. DOI:10.3389/fncel.2018.00148.

NGUYEN J C D, KILLCROSS A S, JENKINS T A. Effect of low-intensity treadmill exercise on behavioural measures and hippocampal parvalbumin immunoreactivity in the rat[J]. Behav Brain Res, 2013, 256: 598-601. DOI:10.1016/j.bbr.2013.09.004.

SELAKOVIC D, JOKSIMOVIC J, ZALETEL I, et al . The opposite effects of nandrolone decanoate and exercise on anxiety levels in rats may involve alterations in hippocampal parvalbumin-positive interneurons[J ] . PLoS One, 2017, 12(12): e0189595. DOI:10.1371/journal.pone.0189595.

TRIPODI M, BHANDARI K, CHOWDHURY A, et al . Parvalbumin interneuron plasticity for consolidation of reinforced learning[J ] . Cold Spring Harb Symp Quant Biol, 2018, 83: 25-35. DOI:10.1101/sqb.2018.83.037630.

LUSSIER S J, STEVENS H E. Delays in GABAergic interneuron development and behavioral inhibition after prenatal stress[J]. Dev Neurobiol, 2016, 76(10): 1078-1091. DOI:10.1002/dneu.22376.

WILLNER P, TOWELL A, SAMPSON D, et al . Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant[J ] . Psychopharmacology, 1987, 93(3): 358-364. DOI:10.1007/BF00187257.

YOHN N L, BLENDY J A. Adolescent chronic unpredictable stress exposure is a sensitive window for long-term changes in adult behavior in mice[J]. Neuropsychopharmacology, 2017, 42(8): 1670-1678. DOI:10.1038/npp.2017.11.

LOGAN R W, EDGAR N, GILLMAN A G, et al . Chronic stress induces brain region-specific alterations of molecular rhythms that correlate with depression-like behavior in mice[J ] . Biol Psychiatry, 2015, 78(4): 249-258. DOI:10.1016/j.biopsych.2015.01.011.

WANG J, TANG J, LIANG X, et al . Hippocampal PGC-1α-mediated positive effects on parvalbumin interneurons are required for the antidepressant effects of running exercise[J ] . Transl Psychiatry, 2021, 11(1): 222. DOI:10.1038/s41398-021-01339-1.

YOOK J S, RAKWAL R, SHIBATO J, et al . Leptin in hippocampus mediates benefits of mild exercise by an antioxidant on neurogenesis and memory[J ] . Proc Natl Acad Sci USA, 2019, 116(22): 10988-10993. DOI:10.1073/pnas.1815197116.

LIU M Y, YIN C Y, ZHU L J, et al . Sucrose preference test for measurement of stress-induced anhedonia in mice[J ] . Nat Protoc, 2018, 13(7): 1686-1698. DOI:10.1038/s41596-018-0011-z.

HARRO J. Animal models of depression: pros and cons[J]. Cell Tissue Res, 2019, 377(1): 5-20. DOI:10.1007/s00441-018-2973-0.

STERU L, CHERMAT R, THIERRY B, et al . The tail suspension test: a new method for screening antidepressants in mice[J ] . Psychopharmacology, 1985, 85(3): 367-370. DOI:10.1007/BF00428203.

ZHU L, FAN J H, CHAO F L, et al . Running exercise protects spinophilin-immunoreactive puncta and neurons in the medial prefrontal cortex of APP/PS 1 transgenic mice[J ] . J Comp Neurol, 2022, 530(6): 858-870. DOI:10.1002/cne.25252..

SONG J, KIM Y K. Animal models for the study of depressive disorder[J]. CNS Neurosci Ther, 2021, 27(6): 633-642. DOI:10.1111/cns.13622.

邓宇辉, 罗艳敏, 梁芯, 等. 海马PGC-1α对小鼠抑郁样行为及海马各亚区星形胶质细胞数量的影响[J]. 陆军军医大学学报, 2022, 44(10): 975-983. DOI:10.16016/j.2097-0927.202110068.

DENG Y H, LUO Y M, LIANG X, et al . Effects of hippocampal PGC-1α on depression-like behaviors and number of astrocytes in hippocampal subregions in mice[J ] . J Army Med Univ, 2022, 44(10): 975-983. DOI:10.16016/j.2097-0927.202110068.

郭一静, 蒋林, 张钐钐, 等. 跑步运动对APP/PS1小鼠内侧前额叶皮质及其小胶质细胞的作用[J]. 陆军军医大学学报, 2022, 44(9): 862-873. DOI:10.16016/j.2097-0927.202110032.

GUO Y J, JIANG L, ZHANG S S, et al . Effects of running on medial prefrontal cortex and microglia in APP/PS 1 mice[J ] . J Army Med Univ, 2022, 44(9): 862-873. DOI:10.16016/j.2097-0927.202110032..

PERIC I, STANISAVLJEVIC A, INTA D, et al . Tianeptine antagonizes the reduction of PV+ and GAD67 cells number in dorsal hippocampus of socially isolated rats[J ] . Prog Neuropsychopharmacol Biol Psychiatry, 2019, 89: 386-399. DOI:10.1016/j.pnpbp.2018.10.013.

TODOROVIC N, MICIC B, SCHWIRTLICH M, et al . Subregion-specific protective effects of fluoxetine and clozapine on parvalbumin expression in medial prefrontal cortex of chronically isolated rats[J ] . Neuroscience, 2019, 396: 24-35. DOI:10.1016/j.neuroscience.2018.11.008.

KANG J, WANG D, DUAN Y C, et al . Aerobic exercise prevents depression via alleviating hippocampus injury in chronic stressed depression rats[J ] . Brain Sci, 2020, 11(1): 9. DOI:10.3390/brainsci11010009..

YI Y D, SONG Y L, LU Y S. Parvalbumin interneuron activation-dependent adulthippocampal neurogenesis is required for treadmill running to reverse schizophrenia-like phenotypes[J]. Front Cell Dev Biol, 2020, 8: 24. DOI:10.3389/fcell.2020.00024.

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跑步对CUS抑郁模型小鼠内侧前额叶皮质内PV+中间神经元的影响

Running exercise shows anti-depressive effect in mice through PV+ interneurons in medial prefrontal cortex

DOI：10.16016/j.2097-0927.202208205

摘要

Abstract

关键词

Keywords

references

跑步对CUS抑郁模型小鼠内侧前额叶皮质内PV⁺中间神经元的影响

Running exercise shows anti-depressive effect in mice through PV⁺ interneurons in medial prefrontal cortex