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Publishing Language: Chinese

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

Lu QIN1, Jing TANG1, Xin LIANG2, Yingqiang QI3, Yanmin LUO4, Qian XIAO5, Dujuan HUANG1, Mei ZHOU1, Yuning ZHOU1, Yong TANG1()
Department of Histology and Embryology, Chongqing Medical University, Chongqing, 400016, China
Department of Pathophysiology, Chongqing Medical University, Chongqing, 400016, China
Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, China
Department of Physiology, Chongqing Medical University, Chongqing, 400016, China
Department of Radioactive Medicine, College of Basic Medical Sciences, Chongqing, 400016, China
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Abstract

Objective

To investigate the effect of running exercise on depression-like behaviors in chronic unpredictable stress（CUS）-induced depression mice and GABAergic interneurons, PV+ 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（P<0.05）, shorter forced swimming immobility time（P<0.05）, and decreased tail suspension immobility time（P<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（P<0.05）.

Conclusion

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

Keywords

mouse CUS model of depressionrunning exercisemedial prefrontal cortexstereologyGABAergic interneuronsPV+ interneurons
CLC number: R322.81;R455;R749.4 Document code: A

References

[1]
MCCARRON R M, SHAPIRO B, RAWLES J, et al. Depression[J]. Ann Intern Med, 2021, 174（5）: AITC202105180. DOI: 10.7326/aitc202105180.
Crossref Google Scholar
[2]
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.
Crossref Google Scholar
[3]
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.
Crossref Google Scholar
[4]
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.
Crossref Google Scholar
[5]
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.
Crossref Google Scholar
[6]
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.
Crossref Google Scholar
[7]
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.
Crossref Google Scholar
[8]
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.
Crossref Google Scholar
[9]
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.
Crossref Google Scholar
[10]
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.
Crossref Google Scholar
[11]
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.
Crossref Google Scholar
[12]
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.
Crossref Google Scholar
[13]
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.
Crossref Google Scholar
[14]
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.
Crossref Google Scholar
[15]
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.
Crossref Google Scholar
[16]
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.
Crossref Google Scholar
[17]
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.
Crossref Google Scholar
[18]
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.
Crossref Google Scholar
[19]
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.
Crossref Google Scholar
[20]
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.
Crossref Google Scholar
[21]
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.
Crossref Google Scholar
[22]
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.
Crossref Google Scholar
[23]
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.
Crossref Google Scholar
[24]
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.
Crossref Google Scholar
[25]
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/PS1 transgenic mice[J]. J Comp Neurol, 2022, 530（6）: 858-870. DOI: 10.1002/cne.25252.
Crossref Google Scholar
[26]
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.
Crossref Google Scholar
[27]
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.
Google Scholar
[28]
GUO Y J, JIANG L, ZHANG S S, et al. Effects of running on medial prefrontal cortex and microglia in APP/PS1 mice[J]. J Army Med Univ, 2022, 44（9）: 862-873. DOI: 10.16016/j.2097-0927.202110032.
Google Scholar
[29]
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.
Crossref Google Scholar
[30]
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.
Crossref Google Scholar
[31]
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.
Crossref Google Scholar
[32]
YI Y D, SONG Y L, LU Y S. Parvalbumin interneuron activation-dependent adult hippocampal 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.
Crossref Google Scholar
Journal of Army Medical University
Volume 45 Issue 3,
February 2023
Pages 209-218
DOI: 10.16016/j.2097-0927.202208205
Cite this article:
QIN L, TANG J, LIANG X, et al. Running exercise shows anti-depressive effect in mice through PV+ interneurons in medial prefrontal cortex. Journal of Army Medical University, 2023, 45(3): 209-218. https://doi.org/10.16016/j.2097-0927.202208205
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