Running exercise shows anti-depressive effect in mice through PV+ interneurons in medial prefrontal cortex
Basic Medicine|更新时间:2026-01-09
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Running exercise shows anti-depressive effect in mice through PV+ interneurons in medial prefrontal cortex
Journal of Army Medical UniversityVol. 45, Issue 3, Pages: 209-218(2023)
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:
基金信息:
the General Program of National Natural Science Foundation of China(82171522);the National Natural Science Foundation for Young Scholars of China(82001436)
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:
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.
Running exercise shows anti-depressive effect in mice through PV+ interneurons in medial prefrontal cortex
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
2
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
2
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)
sh
orter 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
2
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.
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.
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.