Voluntary Running Enhances Hippocampal Proliferation by Increasing Hippocampal NGF, BDNF, and IGF-1

Bo Xu; Xianliang Zhang; Chenghui Song; Fei Liang; Li Zhang

doi:doi:10.11648/j.ab.20170501.11

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Voluntary Running Enhances Hippocampal Proliferation by Increasing Hippocampal NGF, BDNF, and IGF-1

Bo Xu, Xianliang Zhang, Chenghui Song, Fei Liang, Li Zhang

Published in Advances in Biochemistry (Volume 5, Issue 1)

Received: 4 January 2017 Accepted: 25 January 2017 Published: 4 March 2017

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Abstract

Neurotrophic factors and growth factors are known to have positive effects on hippocampal proliferation. However, previous findings on the effects of these factors on exercise-induced hippocampal proliferation are inconsistent. In this study, we investigated the effects of voluntary running on hippocampal proliferation and the expression levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and insulin-like growth factor 1 (IGF-1) in hippocampus. Twenty-four male C57BL/6 mice were randomly divided into four groups: control groups 1 and 2 (C1, n = 6; C2, n = 6) and running groups 1 and 2 (R1, n = 6; R2, n = 6). Mice from C1 and C2 were placed individually in standard cages for eight weeks; mice from R1 and R2 were housed individually in cages with a running wheel for eight weeks. At the fifth week, C1 and R1 mice were injected with BrdU for 7 consecutive days. On the first day of the ninth week, the C1 and R1 mice were anaesthetized and hippocampal neuronal proliferation was assessed using immunohistochemistry; the mice in C2 and R2 were sacrificed to test the expression levels of NGF, BDNF, and IGF-1 mRNA in hippocampus using RT-PCR. The results indicated that voluntary running significantly increased the number of BrdU-positive cells in the dentate gyrus (DG), and significantly upregulated the levels of NGF, BDNF, and IGF-1 mRNA in the hippocampus. In conclusion, our findings indicated that hippocampal proliferation was enhanced by voluntary running, which was associated with increased NGF, BDNF, and IGF-1 mRNA levels in the hippocampus.

Published in	Advances in Biochemistry (Volume 5, Issue 1)
DOI	10.11648/j.ab.20170501.11
Page(s)	1-6
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2017. Published by Science Publishing Group

Keywords

Voluntary Exercise, Hippocampal Proliferation, NGF, BDNF, IGF-1

References

[1]	Kamada M, Li RY, Hashimoto M, Kakuda M, Okada H, Koyanagi Y et al.. Intrinsic and spontaneous neurogenesis in the postnatal slice culture of rat hippocampus. Eur J Neurosci 2004; 20: 2499-2508.
[2]	Zhao C, Deng W, Gage FH. Mechanisms and functional implications of adult neurogenesis. Cell 2008; 132: 645-660.
[3]	Deng W, Aimone JB, Gage FH. New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat Rev Neurosci 2010; 11: 339-350.
[4]	Birch AM, Kelly AM. Chronic intracerebroventricular infusion of nerve growth factor improves recognition memory in the rat. Neuropharmacology 2013; 75: 255-261.
[5]	Choi SH, Li Y, Parada LF, Sisodia SS. Regulation of hippocampal progenitor cell survival, proliferation and dendritic development by BDNF. Mol Neurodegener 2009; 4: 52.
[6]	Aberg MA, Aberg ND, Palmer TD, Alborn AM, Carlsson-Skwirut C, Bang P et al.. IGF-I has a direct proliferative effect in adult hippocampal progenitor cells. Mol Cell Neurosci 2003; 24: 23-40.
[7]	Ji JF, Ji SJ, Sun R, Li K, Zhang Y, Zhang LY et al.. Forced running exercise attenuates hippocampal neurogenesis impairment and the neurocognitive deficits induced by whole-brain irradiation via the BDNF-mediated pathway. Biochem Biophys Res Commun 2014; 443: 646-651.
[8]	Wu CW, Chang YT, Yu L, Chen HI, Jen CJ, Wu SY et al.. Exercise enhances the proliferation of neural stem cells and neurite growth and survival of neuronal progenitor cells in dentate gyrus of middle-aged mice. J Appl Physiol (1985) 2008; 105: 1585-1594.
[9]	Bechara RG, Kelly AM. Exercise improves object recognition memory and induces BDNF expression and cell proliferation in cognitively enriched rats. Behav Brain Res 2013; 245: 96-100.
[10]	Ferreira AF, Real CC, Rodrigues AC, Alves AS, Britto LR. Short-term, moderate exercise is capable of inducing structural, BDNF-independent hippocampal plasticity. Brain Res 2011; 1425: 111-122.
[11]	Marlatt MW, Potter MC, Lucassen PJ, van Praag H. Running throughout middle-age improves memory function, hippocampal neurogenesis, and BDNF levels in female C57BL/6J mice. Dev Neurobiol 2012; 72: 943-952.
[12]	Nakajima S, Ohsawa I, Ohta S, Ohno M, Mikami T. Regular voluntary exercise cures stress-induced impairment of cognitive function and cell proliferation accompanied by increases in cerebral IGF-1 and GST activity in mice. Behav Brain Res 2010; 211: 178-184.
[13]	Trejo JL, Carro E, Torres-Aleman I. Circulating insulin-like growth factor I mediates exercise-induced increases in the number of new neurons in the adult hippocampus. J Neurosci 2001; 21: 1628-1634.
[14]	Neeper SA, Gomez-Pinilla F, Choi J, Cotman CW. Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain. Brain Res 1996; 726: 49-56.
[15]	Yuede CM, Zimmerman SD, Dong H, Kling MJ, Bero AW, Holtzman DM et al.. Effects of voluntary and forced exercise on plaque deposition, hippocampal volume, and behavior in the Tg2576 mouse model of Alzheimer's disease. Neurobiol Dis 2009; 35: 426-432.
[16]	Allen DL, Harrison BC, Maass A, Bell ML, Byrnes WC, Leinwand LA. Cardiac and skeletal muscle adaptations to voluntary wheel running in the mouse. J Appl Physiol (1985) 2001; 90: 1900-1908.
[17]	van Praag H, Kempermann G, Gage FH. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 1999; 2: 266-270.
[18]	van Praag H, Shubert T, Zhao C, Gage FH. Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci 2005; 25: 8680-8685.
[19]	Lou SJ, Liu JY, Chang H, Chen PJ. Hippocampal neurogenesis and gene expression depend on exercise intensity in juvenile rats. Brain Res 2008; 1210: 48-55.
[20]	O'Callaghan RM, Griffin EW, Kelly AM. Long-term treadmill exposure protects against age-related neurodegenerative change in the rat hippocampus. Hippocampus 2009; 19: 1019-1029.
[21]	Kim HG, Oh MS. Memory-enhancing effect of Mori Fructus via induction of nerve growth factor. Br J Nutr 2013; 110: 86-94.
[22]	Scharfman H, Goodman J, Macleod A, Phani S, Antonelli C, Croll S. Increased neurogenesis and the ectopic granule cells after intrahippocampal BDNF infusion in adult rats. Exp Neurol 2005; 192: 348-356.
[23]	Islam O, Loo TX, Heese K. Brain-derived neurotrophic factor (BDNF) has proliferative effects on neural stem cells through the truncated TRK-B receptor, MAP kinase, AKT, and STAT-3 signaling pathways. Curr Neurovasc Res 2009; 6: 42-53.
[24]	Lichtenwalner RJ, Forbes ME, Bennett SA, Lynch CD, Sonntag WE, Riddle DR. Intracerebroventricular infusion of insulin-like growth factor-I ameliorates the age-related decline in hippocampal neurogenesis. Neuroscience 2001; 107: 603-613.
[25]	Carro E, Torres-Aleman I. Serum insulin-like growth factor I in brain function. Keio J Med 2006; 55: 59-63.
[26]	Ding Q, Vaynman S, Akhavan M, Ying Z, Gomez-Pinilla F. Insulin-like growth factor I interfaces with brain-derived neurotrophic factor-mediated synaptic plasticity to modulate aspects of exercise-induced cognitive function. Neuroscience 2006; 140: 823-833.
[27]	Cetinkaya C, Sisman AR, Kiray M, Camsari UM, Gencoglu C, Baykara B et al.. Positive effects of aerobic exercise on learning and memory functioning, which correlate with hippocampal IGF-1 increase in adolescent rats. Neurosci Lett 2013; 549: 177-181.
[28]	Carro E, Trejo JL, Busiguina S, Torres-Aleman I. Circulating insulin-like growth factor I mediates the protective effects of physical exercise against brain insults of different etiology and anatomy. J Neurosci 2001; 21: 5678-5684.
[29]	Choi YS, Cho HY, Hoyt KR, Naegele JR, Obrietan K. IGF-1 receptor-mediated ERK/MAPK signaling couples status epilepticus to progenitor cell proliferation in the subgranular layer of the dentate gyrus. Glia 2008; 56: 791-800.
[30]	Carro E, Nunez A, Busiguina S, Torres-Aleman I. Circulating insulin-like growth factor I mediates effects of exercise on the brain. J Neurosci 2000; 20: 2926-2933.

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APA Style

Bo Xu, Xianliang Zhang, Chenghui Song, Fei Liang, Li Zhang. (2017). Voluntary Running Enhances Hippocampal Proliferation by Increasing Hippocampal NGF, BDNF, and IGF-1. Advances in Biochemistry, 5(1), 1-6. https://doi.org/10.11648/j.ab.20170501.11

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ACS Style

Bo Xu; Xianliang Zhang; Chenghui Song; Fei Liang; Li Zhang. Voluntary Running Enhances Hippocampal Proliferation by Increasing Hippocampal NGF, BDNF, and IGF-1. Adv. Biochem. 2017, 5(1), 1-6. doi: 10.11648/j.ab.20170501.11

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AMA Style

Bo Xu, Xianliang Zhang, Chenghui Song, Fei Liang, Li Zhang. Voluntary Running Enhances Hippocampal Proliferation by Increasing Hippocampal NGF, BDNF, and IGF-1. Adv Biochem. 2017;5(1):1-6. doi: 10.11648/j.ab.20170501.11

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@article{10.11648/j.ab.20170501.11,
  author = {Bo Xu and Xianliang Zhang and Chenghui Song and Fei Liang and Li Zhang},
  title = {Voluntary Running Enhances Hippocampal Proliferation by Increasing Hippocampal NGF, BDNF, and IGF-1},
  journal = {Advances in Biochemistry},
  volume = {5},
  number = {1},
  pages = {1-6},
  doi = {10.11648/j.ab.20170501.11},
  url = {https://doi.org/10.11648/j.ab.20170501.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ab.20170501.11},
  abstract = {Neurotrophic factors and growth factors are known to have positive effects on hippocampal proliferation. However, previous findings on the effects of these factors on exercise-induced hippocampal proliferation are inconsistent. In this study, we investigated the effects of voluntary running on hippocampal proliferation and the expression levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and insulin-like growth factor 1 (IGF-1) in hippocampus. Twenty-four male C57BL/6 mice were randomly divided into four groups: control groups 1 and 2 (C1, n = 6; C2, n = 6) and running groups 1 and 2 (R1, n = 6; R2, n = 6). Mice from C1 and C2 were placed individually in standard cages for eight weeks; mice from R1 and R2 were housed individually in cages with a running wheel for eight weeks. At the fifth week, C1 and R1 mice were injected with BrdU for 7 consecutive days. On the first day of the ninth week, the C1 and R1 mice were anaesthetized and hippocampal neuronal proliferation was assessed using immunohistochemistry; the mice in C2 and R2 were sacrificed to test the expression levels of NGF, BDNF, and IGF-1 mRNA in hippocampus using RT-PCR. The results indicated that voluntary running significantly increased the number of BrdU-positive cells in the dentate gyrus (DG), and significantly upregulated the levels of NGF, BDNF, and IGF-1 mRNA in the hippocampus. In conclusion, our findings indicated that hippocampal proliferation was enhanced by voluntary running, which was associated with increased NGF, BDNF, and IGF-1 mRNA levels in the hippocampus.},
 year = {2017}
}

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TY  - JOUR
T1  - Voluntary Running Enhances Hippocampal Proliferation by Increasing Hippocampal NGF, BDNF, and IGF-1
AU  - Bo Xu
AU  - Xianliang Zhang
AU  - Chenghui Song
AU  - Fei Liang
AU  - Li Zhang
Y1  - 2017/03/04
PY  - 2017
N1  - https://doi.org/10.11648/j.ab.20170501.11
DO  - 10.11648/j.ab.20170501.11
T2  - Advances in Biochemistry
JF  - Advances in Biochemistry
JO  - Advances in Biochemistry
SP  - 1
EP  - 6
PB  - Science Publishing Group
SN  - 2329-0862
UR  - https://doi.org/10.11648/j.ab.20170501.11
AB  - Neurotrophic factors and growth factors are known to have positive effects on hippocampal proliferation. However, previous findings on the effects of these factors on exercise-induced hippocampal proliferation are inconsistent. In this study, we investigated the effects of voluntary running on hippocampal proliferation and the expression levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and insulin-like growth factor 1 (IGF-1) in hippocampus. Twenty-four male C57BL/6 mice were randomly divided into four groups: control groups 1 and 2 (C1, n = 6; C2, n = 6) and running groups 1 and 2 (R1, n = 6; R2, n = 6). Mice from C1 and C2 were placed individually in standard cages for eight weeks; mice from R1 and R2 were housed individually in cages with a running wheel for eight weeks. At the fifth week, C1 and R1 mice were injected with BrdU for 7 consecutive days. On the first day of the ninth week, the C1 and R1 mice were anaesthetized and hippocampal neuronal proliferation was assessed using immunohistochemistry; the mice in C2 and R2 were sacrificed to test the expression levels of NGF, BDNF, and IGF-1 mRNA in hippocampus using RT-PCR. The results indicated that voluntary running significantly increased the number of BrdU-positive cells in the dentate gyrus (DG), and significantly upregulated the levels of NGF, BDNF, and IGF-1 mRNA in the hippocampus. In conclusion, our findings indicated that hippocampal proliferation was enhanced by voluntary running, which was associated with increased NGF, BDNF, and IGF-1 mRNA levels in the hippocampus.
VL  - 5
IS  - 1
ER  -

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Author Information

Bo Xu

Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai, China
Xianliang Zhang

College of Physical Education, Shandong University, Jinan, China
Chenghui Song

Department of Neuroscience, the Scripps Research Institute, Jupiter, Florida, USA
Fei Liang

School of Physical Education & Health Care, East China Normal University, Shanghai, China
Li Zhang

Division of Physical Education, China University of Mining & Technology, Beijing, China

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APA Style

Bo Xu, Xianliang Zhang, Chenghui Song, Fei Liang, Li Zhang. (2017). Voluntary Running Enhances Hippocampal Proliferation by Increasing Hippocampal NGF, BDNF, and IGF-1. Advances in Biochemistry, 5(1), 1-6. https://doi.org/10.11648/j.ab.20170501.11

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ACS Style

Bo Xu; Xianliang Zhang; Chenghui Song; Fei Liang; Li Zhang. Voluntary Running Enhances Hippocampal Proliferation by Increasing Hippocampal NGF, BDNF, and IGF-1. Adv. Biochem. 2017, 5(1), 1-6. doi: 10.11648/j.ab.20170501.11

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AMA Style

Bo Xu, Xianliang Zhang, Chenghui Song, Fei Liang, Li Zhang. Voluntary Running Enhances Hippocampal Proliferation by Increasing Hippocampal NGF, BDNF, and IGF-1. Adv Biochem. 2017;5(1):1-6. doi: 10.11648/j.ab.20170501.11

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@article{10.11648/j.ab.20170501.11,
  author = {Bo Xu and Xianliang Zhang and Chenghui Song and Fei Liang and Li Zhang},
  title = {Voluntary Running Enhances Hippocampal Proliferation by Increasing Hippocampal NGF, BDNF, and IGF-1},
  journal = {Advances in Biochemistry},
  volume = {5},
  number = {1},
  pages = {1-6},
  doi = {10.11648/j.ab.20170501.11},
  url = {https://doi.org/10.11648/j.ab.20170501.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ab.20170501.11},
  abstract = {Neurotrophic factors and growth factors are known to have positive effects on hippocampal proliferation. However, previous findings on the effects of these factors on exercise-induced hippocampal proliferation are inconsistent. In this study, we investigated the effects of voluntary running on hippocampal proliferation and the expression levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and insulin-like growth factor 1 (IGF-1) in hippocampus. Twenty-four male C57BL/6 mice were randomly divided into four groups: control groups 1 and 2 (C1, n = 6; C2, n = 6) and running groups 1 and 2 (R1, n = 6; R2, n = 6). Mice from C1 and C2 were placed individually in standard cages for eight weeks; mice from R1 and R2 were housed individually in cages with a running wheel for eight weeks. At the fifth week, C1 and R1 mice were injected with BrdU for 7 consecutive days. On the first day of the ninth week, the C1 and R1 mice were anaesthetized and hippocampal neuronal proliferation was assessed using immunohistochemistry; the mice in C2 and R2 were sacrificed to test the expression levels of NGF, BDNF, and IGF-1 mRNA in hippocampus using RT-PCR. The results indicated that voluntary running significantly increased the number of BrdU-positive cells in the dentate gyrus (DG), and significantly upregulated the levels of NGF, BDNF, and IGF-1 mRNA in the hippocampus. In conclusion, our findings indicated that hippocampal proliferation was enhanced by voluntary running, which was associated with increased NGF, BDNF, and IGF-1 mRNA levels in the hippocampus.},
 year = {2017}
}

Copy | Download

TY  - JOUR
T1  - Voluntary Running Enhances Hippocampal Proliferation by Increasing Hippocampal NGF, BDNF, and IGF-1
AU  - Bo Xu
AU  - Xianliang Zhang
AU  - Chenghui Song
AU  - Fei Liang
AU  - Li Zhang
Y1  - 2017/03/04
PY  - 2017
N1  - https://doi.org/10.11648/j.ab.20170501.11
DO  - 10.11648/j.ab.20170501.11
T2  - Advances in Biochemistry
JF  - Advances in Biochemistry
JO  - Advances in Biochemistry
SP  - 1
EP  - 6
PB  - Science Publishing Group
SN  - 2329-0862
UR  - https://doi.org/10.11648/j.ab.20170501.11
AB  - Neurotrophic factors and growth factors are known to have positive effects on hippocampal proliferation. However, previous findings on the effects of these factors on exercise-induced hippocampal proliferation are inconsistent. In this study, we investigated the effects of voluntary running on hippocampal proliferation and the expression levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and insulin-like growth factor 1 (IGF-1) in hippocampus. Twenty-four male C57BL/6 mice were randomly divided into four groups: control groups 1 and 2 (C1, n = 6; C2, n = 6) and running groups 1 and 2 (R1, n = 6; R2, n = 6). Mice from C1 and C2 were placed individually in standard cages for eight weeks; mice from R1 and R2 were housed individually in cages with a running wheel for eight weeks. At the fifth week, C1 and R1 mice were injected with BrdU for 7 consecutive days. On the first day of the ninth week, the C1 and R1 mice were anaesthetized and hippocampal neuronal proliferation was assessed using immunohistochemistry; the mice in C2 and R2 were sacrificed to test the expression levels of NGF, BDNF, and IGF-1 mRNA in hippocampus using RT-PCR. The results indicated that voluntary running significantly increased the number of BrdU-positive cells in the dentate gyrus (DG), and significantly upregulated the levels of NGF, BDNF, and IGF-1 mRNA in the hippocampus. In conclusion, our findings indicated that hippocampal proliferation was enhanced by voluntary running, which was associated with increased NGF, BDNF, and IGF-1 mRNA levels in the hippocampus.
VL  - 5
IS  - 1
ER  -

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