Advertisement

Transcranial Magneto-Acoustic Stimulation Improves Neuroplasticity in Hippocampus of Parkinson’s Disease Model Mice

  • Yuexiang Wang
  • Lina Feng
  • Shikun Liu
  • Xiaoqing Zhou
  • Tao Yin
  • Zhipeng LiuEmail author
  • Zhuo YangEmail author
Original Article

Abstract

In this study, we have, for the first time, demonstrated the beneficial effects of transcranial magneto-acoustic stimulation (TMAS), a technique based on focused ultrasound stimulation within static magnetic field, on the learning and memory abilities and neuroplasticity of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease (PD). Our results showed that chronic TMAS treatment (2 weeks) improved the outcome of Morris water maze, long-term potentiation (LTP), and dendritic spine densities in the dentate gyrus (DG) region of the hippocampus of PD model mice. To further investigate into the underlying mechanisms of these beneficial effects by TMAS, we quantified the proteins in the hippocampus that regulated neuroplasticity. Results showed that the level of postsynaptic density protein 95 was elevated in the brain of TMAS-treated PD model mice while the level of synaptophysin (SYP) did not show any change. We further quantified proteins that mediated neuroplasticity mechanisms, such as brain-derived neurotrophic factor (BDNF) and other important proteins that mediated neuroplasticity. Results showed that TMAS treatment elevated the levels of BDNF, cAMP response element–binding protein (CREB), and protein kinase B (p-Akt) in the PD model mouse hippocampus, but not in the non-PD mouse hippocampus. These results suggest that the beneficial effects on the neuroplasticity of PD model mice treated with TMAS could possibly be conducted through postsynaptic regulations and mediated by BDNF.

Keywords

Transcranial magneto-acoustic stimulation (TMAS) long-term potentiation (LTP) dendritic spine brain-derived neurotrophic factor (BDNF) hippocampus 

Notes

Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (81771979 and 81571804 to Z. Yang, 61501523 to X. Zhou, and 81772003 to T. Yin) and China Postdoctoral Science Foundation (2016M601250 to Y. Wang).

Required Author Forms

Disclosure forms provided by the authors are available with the online version of this article.

Supplementary material

13311_2019_732_MOESM1_ESM.pdf (544 kb)
ESM 1 (PDF 544 kb)
13311_2019_732_MOESM2_ESM.pdf (508 kb)
ESM 2 (PDF 507 kb)

References

  1. 1.
    Dauer W, Przedborski S. Parkinson’s disease: mechanisms and models. Neuron, 2003. 39: 889–909.CrossRefGoogle Scholar
  2. 2.
    Davie CA. A review of Parkinson’s disease. Br Med Bull, 2008. 86: 109–127.CrossRefGoogle Scholar
  3. 3.
    Miocinovic S, Somayajula S, Chitnis S, Vitek JL. History, applications, and mechanisms of deep brain stimulation. JAMA Neurol, 2013. 70: 163–171.CrossRefGoogle Scholar
  4. 4.
    Perlmutter JS, Mink JW. Deep brain stimulation. Annu Rev Neurosci, 2006. 29: 229–257.CrossRefGoogle Scholar
  5. 5.
    Hallett M. Transcranial magnetic stimulation and the human brain. Nature, 2000. 406: 147–50.CrossRefGoogle Scholar
  6. 6.
    Rossini PM, Rossini L, Ferreri F. Transcranial magnetic stimulation: a review. IEEE Eng Med Biol Mag, 2010. 29: 84–95.CrossRefGoogle Scholar
  7. 7.
    Leite J, Simis M, Carvalho S, Fregni F. Chapter 134 - transcranial magnetic stimulation, in Neuromodulation (2), Krames ES, Peckham PH, Rezai AR, Editors. 2018, Academic Press. p. 1577–1587.Google Scholar
  8. 8.
    Bystritsky A, Korb AS, Douglas PK, et al. A review of low-intensity focused ultrasound pulsation. Brain Stimul, 2011. 4: 125–136.CrossRefGoogle Scholar
  9. 9.
    Yang T, Chen J, Yan B, Zhou D. Transcranial ultrasound stimulation: a possible therapeutic approach to epilepsy. Med Hypotheses, 2011. 76: 381–383.CrossRefGoogle Scholar
  10. 10.
    Martin E, Jeanmonod D, Morel A, Zadicario E, Werner B. High-intensity focused ultrasound for noninvasive functional neurosurgery. Ann Neurol, 2010. 66: 858–861.CrossRefGoogle Scholar
  11. 11.
    Guo T, Li H, Lv Y, et al. Pulsed Transcranial Ultrasound Stimulation Immediately After The Ischemic Brain Injury is Neuroprotective. IEEE Trans Biomed Eng, 2015. 62: 2352–2357.CrossRefGoogle Scholar
  12. 12.
    Yuan Y, Chen Y, Li X. Theoretical analysis of transcranial magneto-acoustical stimulation with Hodgkin-Huxley Neuron Model. Front Comput Neurosci, 2016. 10: 35.CrossRefGoogle Scholar
  13. 13.
    Norton SJ. Can ultrasound be used to stimulate nerve tissue? Biomed Eng Online, 2003. 2: 6–6.CrossRefGoogle Scholar
  14. 14.
    Foerde K, Shohamy D. The role of the basal ganglia in learning and memory: insight from Parkinson’s disease. Neurobiol Learn Mem, 2011. 96: 624–636.CrossRefGoogle Scholar
  15. 15.
    Squire LR. Memory systems of the brain: a brief history and current perspective. Neurobiol Learn Mem, 2004. 82: 171–177.CrossRefGoogle Scholar
  16. 16.
    Sedelis M, Schwarting RKW, Huston JP. Behavioral phenotyping of the MPTP mouse model of Parkinson’s disease. Behav Brain Res, 2001. 125: 109–125.CrossRefGoogle Scholar
  17. 17.
    Matsuura K, Kabuto H, Makino H, Ogawa N. Pole test is a useful method for evaluating the mouse movement disorder caused by striatal dopamine depletion. J Neurosci Methods, 1997. 73: 45–48.CrossRefGoogle Scholar
  18. 18.
    Sedelis M, Hofele K, Auburger GW, Morgan S, Huston JP, Schwarting RKW. MPTP Susceptibility in the Mouse: Behavioral, Neurochemical, and Histological Analysis of Gender and Strain Differences. Behav Genet, 2000. 30: 171–182.CrossRefGoogle Scholar
  19. 19.
    Li H, Zhou X, Zhang S, Ma R, Yin T, Liu Z. Approach for focused electric stimulation based on the magneto-acoustic effect. J Biomed Eng Res, 2015: 201–206.Google Scholar
  20. 20.
    Zhu G, Huang Y, Chen Y, Zhuang Y, Behnisch T. MPTP modulates hippocampal synaptic transmission and activity-dependent synaptic plasticity via dopamine receptors. J Neurochem, 2012. 122: 582–593.CrossRefGoogle Scholar
  21. 21.
    Han G, An L, Yang B, Si L, Zhang T. Nicotine-induced impairments of spatial cognition and long-term potentiation in adolescent male rats. Hum Exp Toxicol, 2013. 33: 203–213.CrossRefGoogle Scholar
  22. 22.
    Gao J, Zhang X, Yu M, Ren G, Yang Z. Cognitive deficits induced by multi-walled carbon nanotubes via the autophagic pathway. Toxicology, 2015. 337: 21–29.CrossRefGoogle Scholar
  23. 23.
    Narayanan SN, Jetti R, Gorantla VR, Kumar RS, Nayak S, Bhat PG. Appraisal of the effect of brain impregnation duration on neuronal staining and morphology in a modified Golgi–Cox method. J Neurosci Methods, 2014. 235: 193–207.CrossRefGoogle Scholar
  24. 24.
    Rodriguez A, Ehlenberger DB, Dickstein DL, Hof PR, Wearne SL. Automated three-dimensional detection and shape classification of dendritic spines from fluorescence microscopy images. PLoS One, 2008. 3: e1997.CrossRefGoogle Scholar
  25. 25.
    Dumitriu D, Rodriguez A, Morrison J. High-throughput, detailed, cell-specific neuroanatomy of dendritic spines using microinjection and confocal microscopy. Nat Protoc, 2011. 6: 1391–411.CrossRefGoogle Scholar
  26. 26.
    Cunha C, Brambilla R, Thomas K. A simple role for BDNF in learning and memory? Front Mol Neurosci, 2010. 3: 1.Google Scholar
  27. 27.
    Lu B. BDNF and activity-dependent synaptic modulation. Learn Mem, 2003. 10: 86–98.CrossRefGoogle Scholar
  28. 28.
    Leßmann V, Brigadski T. Mechanisms, locations, and kinetics of synaptic BDNF secretion: An update. Neurosci Res, 2009. 65: 11–22.CrossRefGoogle Scholar
  29. 29.
    Gottmann K, Mittmann T, Lessmann V. BDNF signaling in the formation, maturation and plasticity of glutamatergic and GABAergic synapses. Exp Brain Res, 2009. 199: 203–234.CrossRefGoogle Scholar
  30. 30.
    Carlezon WA, Jr, Duman RS, Nestler EJ. The many faces of CREB. Trends Neurosci 28: 436–445.Google Scholar
  31. 31.
    Li F, Tsien JZ. Memory and the NMDA receptors. N Engl J Med, 2009. 361: 302–303.CrossRefGoogle Scholar
  32. 32.
    Cull-Candy S, Brickley S, Farrant M. NMDA receptor subunits: diversity, development and disease. Curr Opin Neurobiol, 2001. 11: 327–335.CrossRefGoogle Scholar
  33. 33.
    Furukawa H, Singh SK, Mancusso R, Gouaux E. Subunit arrangement and function in NMDA receptors. Nature, 2005. 438: 185.CrossRefGoogle Scholar
  34. 34.
    Loftis JM, Janowsky A. The N-methyl-d-aspartate receptor subunit NR2B: localization, functional properties, regulation, and clinical implications. Pharmacol Ther, 2003. 97: 55–85.CrossRefGoogle Scholar
  35. 35.
    Paoletti P, Neyton J. NMDA receptor subunits: function and pharmacology. Curr Opin Pharmacol, 2007. 7: 39–47.CrossRefGoogle Scholar
  36. 36.
    Liu X-B, Murray KD, Jones EG. Switching of NMDA receptor 2A and 2B subunits at thalamic and cortical synapses during early postnatal development. J Neurosci, 2004. 24: 8885.CrossRefGoogle Scholar
  37. 37.
    Fry WJ, Barnard JW, Fry FJ, Brennan JF. Ultrasonically produced localized selective lesions in the central nervous system. Am J Phys Med, 1955. 34: 413–423.Google Scholar
  38. 38.
    Gavrilov LR, Gersuni GV, Ilyinsky OB, Sirotyuk MG, Tsirulnikov EM, Shchekanov EE. The effect of focused ultrasound on the skin and deep nerve structures of man and animal. Prog Brain Res, 1976. 43: 279–292.CrossRefGoogle Scholar
  39. 39.
    Fry WJ. Intense ultrasound in investigations of the central nervous system. Adv Biol Med Phys, 1959. 6: 281–348.CrossRefGoogle Scholar
  40. 40.
    Fry WJ. Use of intense ultrasound in neurological research. Am J Phys Med, 1958. 37: 143–147.Google Scholar
  41. 41.
    Haar GT. Therapeutic applications of ultrasound. Prog Biophys Mol Biol, 2007. 93: 111–29.CrossRefGoogle Scholar
  42. 42.
    Dalecki D. Mechanical bioeffects of ultrasound. Annu Rev Biomed Eng, 2004. 6 229.CrossRefGoogle Scholar
  43. 43.
    Su WS, Wu CH, Chen SF, Yang FY. Transcranial ultrasound stimulation promotes brain-derived neurotrophic factor and reduces apoptosis in a mouse model of traumatic brain injury. Brain Stimul, 2017.Google Scholar
  44. 44.
    Scarcelli T, Jordão JF, O’Reilly MA, Ellens N, Hynynen K, Aubert I. Stimulation of hippocampal neurogenesis by transcranial focused ultrasound and microbubbles in adult mice. Brain Stimul, 2014. 7 304–307.CrossRefGoogle Scholar
  45. 45.
    Wang Y, Ren B, Wu S, Zhong Q, Li X, Lu C. The Effects of transcranial ultrasound stimulation on motor functioning and anti-oxidative capacity in mice with Parkinson’s disease. Chin J Phys Med Rehabil, 2015. 37 488–92.Google Scholar
  46. 46.
    Bailey MR, Dalecki D, Child SZ, Raeman CH, Penney DP, Blackstock DT, Carstensen EL. Bioeffects of positive and negative acoustic pressures in vivo. J Acoust Soc Am, 1996. 100 3941–3946.CrossRefGoogle Scholar
  47. 47.
    Wall PD, Fry WJ, Stephens R, Tucker D, Lettvin JY. Changes produced in the central nervous system by ultrasound. Sci, 1951. 114 686.CrossRefGoogle Scholar
  48. 48.
    Gulick DW, Li T, Kleim JA, Towe BC. Comparison of electrical and ultrasound neurostimulation in rat motor cortex. Ultrasound Med Biol, 2017. 43 2824–2833.CrossRefGoogle Scholar
  49. 49.
    Farahna M, Ali Omer MA, Ali Omer MA, et al. The effects of static magnetic field on rats brain, lungs, liver, Pancreas Blood Electrolytes Neuroquantol, 2014. 12 230–236.Google Scholar
  50. 50.
    Brandeis R, Brandys Y, Yehuda S. The use of the Morris Water Maze in the study of memory and learning. Int J Neurosci, 1989. 48 29.CrossRefGoogle Scholar
  51. 51.
    Deguil J, Chavant F, Lafay-Chebassier C, Pérault-Pochat M-C, Fauconneau B, Pain S. Neuroprotective effect of PACAP on translational control alteration and cognitive decline in MPTP Parkinsonian mice. Neurotox Res, 2009. 17 142–155.CrossRefGoogle Scholar
  52. 52.
    Dluzen DE, Kreutzberg JD. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) disrupts social memory/recognition processes in the male mouse. Brain Res, 1993. 609: 98.CrossRefGoogle Scholar
  53. 53.
    Prediger RDS, Aguiar AS, Rojas-Mayorquin AE, et al. Single Intranasal Administration of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine in C57BL/6 Mice Models Early Preclinical Phase of Parkinson’s Disease. Neurotox Res, 2009. 17 114–129.CrossRefGoogle Scholar
  54. 54.
    Tanila H, ., Björklund M, ., Riekkinen P, . Cognitive changes in mice following moderate MPTP exposure. Brain Res Bull, 1998. 45 577–582.CrossRefGoogle Scholar
  55. 55.
    Bliss TV, Collingridge GL. A synaptic model of memory: long-term potentiation in the hippocampus. Nature, 1993. 361 31–39.CrossRefGoogle Scholar
  56. 56.
    Moriguchi S, Yabuki Y, Fukunaga K. Reduced calcium/calmodulin-dependent protein kinase II activity in the hippocampus is associated with impaired cognitive function in MPTP-treated mice. J Neurochem, 2012. 120 541–551.CrossRefGoogle Scholar
  57. 57.
    Zhu G, Chen Y, Huang Y, Li Q, Behnisch T. MPTP-meditated hippocampal dopamine deprivation modulates synaptic transmission and activity-dependent synaptic plasticity. Toxicol Appl Pharmacol, 2011. 254 332–341.CrossRefGoogle Scholar
  58. 58.
    Zhu G, Li J, He L, Wang X, Hong X. MPTP-induced changes in hippocampal synaptic plasticity and memory are prevented by memantine through the BDNF-TrkB pathway. Br J Pharmacol, 2015. 172 2354–2368.CrossRefGoogle Scholar
  59. 59.
    Kida S. A functional role for CREB as a positive regulator of memory formation and LTP. Exp Neurobiol, 2012. 21: 136–140.CrossRefGoogle Scholar

Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2019

Authors and Affiliations

  1. 1.College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular RegulationNankai UniversityTianjinChina
  2. 2.Institute of Biomedical EngineeringChinese Academy of Medical Sciences & Peking Union Medical CollegeTianjinChina

Personalised recommendations