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01-05-2014 | Original Article

Effect of treadmill exercise on 5-HT, 5-HT1A receptor and brain derived neurophic factor in rats after permanent middle cerebral artery occlusion

Authors: Xiaofang Lan, Meng Zhang, Wan Yang, Zongju Zheng, Yuan Wu, Qian Zeng, Shudong Liu, Ke Liu, Guangqin Li

Published in: Neurological Sciences | Issue 5/2014

Abstract

It has been well documented that exercise promotes neurological rehabilitation in patients with cerebral ischemia. However, the exact mechanisms have not been fully elucidated. This study aimed to discuss the effect of treadmill exercise on expression levels of 5-HT, 5-HT1A receptor (5-HT1AR) and brain derived neurophic factor (BDNF) in rat brains after permanent middle cerebral artery occlusion (pMCAO). A total of 55 rats were randomly divided into 3 groups: pMCAO group, pMCAO and treadmill exercise (pMCAO + Ex) group, and sham-operated group. Rats in pMCAO + Ex group underwent treadmill exercise for 16 days. Neurological function was evaluated by modified Neurological Severity Scores (mNSS). High-performance liquid chromatography-electrochemical detection system was used to determine the content of 5-HT in cortex tissues. The protein levels of 5-HT1AR, BDNF and synaptophysin were measured by Western blot. The mNSS in pMCAO + Ex group was lower than that in pMCAO group on day 19 post-MCAO (p < 0.001). The content of 5-HT dropped to 3.81 ± 1.86 ng/ml in pMCAO group (43.84 ± 2.05 ng/ml in sham-operated group), but increased in pMCAO + Ex group (10.06 ± 1.80 ng/ml). The protein expressions levels of synaptophysin, 5-HT1AR and BDNF were downregulated after cerebral ischemia (p < 0.05), and upregulated after treadmill exercise (p < 0.05). These results indicate that treadmill exercise improves neurologic function, enhances neuronal plasticity and upregulates the levels of 5-HT, 5-HT1AR and BDNF in rats with pMCAO.

Matsuda F, Sakakima H, Yoshida Y (2011) The effects of early exercise on brain damage and recovery after focal cerebral infarction in rats. Acta Physiol (Oxf) 201:275–287CrossRef

Ferreira AF, Real CC, Rodrigues AC, Alves AS, Britto LR (2010) Moderate exercise changes synaptic and cytoskeletal proteins in motor regions of the rat brain. Brain Res 1361:31–42PubMedCrossRef

Tang Q, Yang Q, Hu Z, Liu B, Shuai J, Wang G, Liu Z, Xia J, Shen X (2007) The effects of willed movement therapy on AMPA receptor properties for adult rat following focal cerebral ischemia. Behav Brain Res 181:254–261PubMedCrossRef

Vitalis T, Parnavelas JG (2003) The role of serotonin in early cortical development. Dev Neurosci 25:245–256PubMedCrossRef

Azmitia EC (2001) Modern views on an ancient chemical: serotonin effects on cell proliferation, maturation, and apoptosis. Brain Res Bull 56:413–424PubMedCrossRef

Harrison MJ, Marsdon CD, Jenner P (1979) Effect of experimental ischemia on neurotransmitter amines in the gerbil brain. Stroke 10:165–168PubMedCrossRef

Kanthan R, Shuaib A, Griebel R, el-Alazounni H, Miyashita H, Kalra J (1996) Evaluation of monoaminergic neurotransmitters in the acute focal ischemic human brain model by intracerebral in vivo microdialysis. Neurochem Res 21:563–566PubMedCrossRef

Chen HI, Lin LC, Yu L, Liu YF, Kuo YM, Huang AM, Chuang JI, Wu FS, Liao PC, Jen CJ (2008) Treadmill exercise enhances passive avoidance learning in rats: the role of down-regulated serotonin system in the limbic system. Neurobiol Learn Mem 89:489–496PubMedCrossRef

Baek SS, Jun TW, Kim KJ, Shin MS, Kang SY, Kim CJ (2012) Effects of postnatal treadmill exercise on apoptotic neuronal cell death and cell proliferation of maternal-separated rat pups. Brain Dev 34:45–56PubMedCrossRef

10.

Berchtold NC, Chinn G, Chou M, Kesslak JP, Cotman CW (2005) Exercise primes a molecular memory for brain-derived neurotrophic factor protein induction in the rat hippocampus. Neuroscience 133:853–861PubMedCrossRef

11.

Mattson MP, Maudsley S, Martin B (2004) BDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurodegenerative disorders. Trends Neurosci 27:589–594PubMedCrossRef

12.

Salazar-Colocho P, Del Río J, Frechilla D (2008) Neuroprotective effects of serotonin 5-HT1A receptor activation against ischemic cell damage in gerbil hippocampus: involvement of NMDA receptor NR1 subunit and BDNF. Brain Res 1199:159–166PubMedCrossRef

13.

Marco I, Valhondo M, Martin-Fontecha M, Vazquez-Villa H, Del Rio J, Planas A, Sagredo O, Ramos JA, Torrecillas IR, Pardo L, Frechilla D, Benhamú B, López-Rodríguez ML (2011) New serotonin 5-HT(1A) receptor agonists with neuroprotective effect against ischemic cell damage. J Med Chem 54:7986–7999PubMedCrossRef

14.

Galter D, Unsicker K (2000) Sequential activation of the 5-HT1(A) serotonin receptor and TrkB induces the serotonergic neuronal phenotype. Mol Cell Neurosci 15:446–455PubMedCrossRef

15.

Longa EZ, Weinstein PR, Carlson S, Cummins R (1989) Reversible middle cerebral artery occlusion without craniectomy in rat. Stroke 20:84–91PubMedCrossRef

16.

Chen J, Li Y, Wang L, Zhang Z, Lu D, Lu M, Chopp M (2001) Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke 32:1005–1011PubMedCrossRef

17.

Chang HC, Yang YR, Wang SG, Wang RY (2009) Effects of treadmill training on motor performance and extracellular glutamate level in striatum in rats with or without transient middle cerebral artery occlusion. Behav Brain Res 205:450–455PubMedCrossRef

18.

Jia J, Hu YS, Wu Y, Yu HX, Liu G, Zhu DN, Xia CM, Cao ZJ, Zhang X, Guo QC (2010) Treadmill pre-training suppresses the release of glutamate resulting from cerebral ischemia in rats. Exp Brain Res 204:173–179PubMedCrossRef

19.

Cotman CW, Berchtold NC (2002) Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci 25:295–301PubMedCrossRef

20.

Farmer J, Zhao X, van Praag H, Wodtke K, Gage FH, Christie BR (2004) Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague-Dawley rats in vivo. Neuroscience 124:71–79PubMedCrossRef

21.

Matsuda F, Sakakima H, Yoshida Y (2011) The effects of early exercise on brain damage and recovery after focal cerebral infarction in rats. Acta Physiol (Oxf) 201:275–287CrossRef

22.

Compan V (2007) Serotonin receptors in neurobiology. CRC Press, Boca Raton

23.

Wiedenmann B, Franke WW (1985) Identification and localization of synaptophysin, an integral membrane glycoprotein of Mr 38,000 characteristic of presynaptic vesicles. Cell 41:1017–1028PubMedCrossRef

24.

Marin R, Williams A, Hale S, Burge B, Mense M, Bauman R, Tortella F (2003) The effect of voluntary exercise exposure on histological and neurobehavioral outcomes after ischemic brain injury in the rat. Physiol Behav 80:167–175PubMedCrossRef

25.

Briones TL, Woods J, Wadowska M, Rogozinska M, Nguyen M (2006) Astrocytic changes in the hippocampus and functional recovery after cerebral ischemia are facilitated by rehabilitation training. Behav Brain Res 171:17–25PubMedCrossRef

26.

Kim MW, Bang MS, Han TR, Ko YJ, Yoon BW, Kim JH, Kang LM, Lee KM, Kim MH (2005) Exercise increased BDNF and trkB in the contralateral hemisphere of the ischemic rat brain. Brain Res 1052:16–21PubMedCrossRef

27.

Rasmussen P, Brassard P, Adser H, Pedersen MV, Leick L, Hart E, Secher NH, Pedersen BK, Pilegaard H (2009) Evidence for a release of brain-derived neurotrophic factor from the brain during exercise. Exp Physiol 94:1062–1069PubMedCrossRef

28.

Combs C, Ke Z, Yip SP, Li L, Zheng XX, Tong KY (2011) The effects of voluntary, involuntary, and forced exercises on brain-derived neurotrophic factor and motor function recovery: a rat brain ischemia model. PLoS ONE 6:e16643. doi:10.1371/journal.pone.0016643 CrossRef

29.

Yang YR, Wang RY, Wang PS (2003) Early and late treadmill training after focal brain ischemia in rats. Neurosci Lett 339:91–94PubMedCrossRef

30.

Sundseth A, Thommessen B, Ronning OM (2012) Outcome after mobilization within 24 hours of acute stroke: a randomized controlled trial. Stroke 43:2389–2394PubMedCrossRef

31.

Cowen DS (2007) Serotonin and neuronal growth factors—a convergence of signaling pathways. J Neurochem 101:1161–1171PubMedCrossRef

32.

Burke TF, Advani T, Adachi M, Monteggia LM, Hensler JG (2012) Sensitivity of hippocampal 5-HT1A receptors to mild stress in BDNF-deficient mice. Int J Neuropsychopharmacol 1–15. doi:10.1017/s1461145712000466

33.

Wu YC, Hill RA, Klug M, van den Buuse M (2012) Sex-specific and region-specific changes in BDNF–TrkB signalling in the hippocampus of 5-HT1A receptor and BDNF single and double mutant mice. Brain Res 1452:10–17. doi:10.1016/j.brainres.2012.03.011 PubMedCrossRef

Title: Effect of treadmill exercise on 5-HT, 5-HT1A receptor and brain derived neurophic factor in rats after permanent middle cerebral artery occlusion
Authors: Xiaofang Lan
Meng Zhang
Wan Yang
Zongju Zheng
Yuan Wu
Qian Zeng
Shudong Liu
Ke Liu
Guangqin Li
Publication date: 01-05-2014
Publisher: Springer Milan
Published in: Neurological Sciences / Issue 5/2014
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-013-1599-y

At a glance: The STEP trials

Springer Medicine

Effect of treadmill exercise on 5-HT, 5-HT1A receptor and brain derived neurophic factor in rats after permanent middle cerebral artery occlusion

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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