Journal of the Korea Academia-Industrial cooperation Society (한국산학기술학회논문지)

The Korea Academia-Industrial cooperation Society (한국산학기술학회)
권호 표지
DOI QR코드

DOI QR Code

Effect of Microcurrent Wave Superposition on Cognitive Improvement in Alzheimer's Disease Mice Model

알츠하이머 질환 마우스에서 중첩주파수를 활용한 미세전류가 인지능력 개선에 미치는 효과

  • Kim, Min Jeong (Department of Food Science and Nutrition, Pusan National University) ;
  • Lee, Ah Young (Department of Food Science, Gyeongnam National University of Science and Technology) ;
  • Cho, Dong Shik (Natural Well Tech. Co. Ltd) ;
  • Cho, Eun Ju (Department of Food Science and Nutrition, Pusan National University)
  • 김민정 (부산대학교 식품영양학과) ;
  • 이아영 (경남과학기술대학교 식품과학부) ;
  • 조동식 ((주)내츄럴웰테크) ;
  • 조은주 (부산대학교 식품영양학과)
  • Received : 2019.02.12
  • Accepted : 2019.05.03
  • Published : 2019.05.31
Download PDF
⟨ Previous Next ⟩

Abstract

In the present study, we investigated the effect of microcurrent against cognitive impairment in Alzheimer's disease (AD) mice model. The cognitive impairment was induced by intracerebroventricularly injection of amyloid beta ($A{\beta}$) to ICR mouse brain, and four kinds of micorocurrent wave were applied to AD mice. We observed the improved cognitive ability in microcurrent-applied AD mice through novel object recognition test and Morris water maze test, compared to $A{\beta}$-injected control group. The contents of malondialdehyde generated by $A{\beta}$ in the brain were also reduced by microcurrent application. These effects of microcurrent were related to the modulation of $A{\beta}$ producing and brain-derived neurotrophic factor (BDNF). Microcurrent down-regulated ${\beta}$-secretase, presenilin 1, and presenilin 2 which were related amyloidogenic pathway, and up-regulated human brain-derived neurotrophic factor in the mice brain, especially Wave4 group [STEP FORM wave form (0, 1.5, 3, 5V), wave superposition]. These results suggest that microcurrent application could provide help for improvement learning and memory ability, at least partly.

본 연구에서는 Alzheimer's disease(AD) 마우스 모델에서 미세전류의 적용을 통한 인지능력 개선 효과를 확인하였다. ICR 마우스에 amyloid beta($A{\beta}$)를 뇌 내 주입하여 인지능력 손상을 유도한 후, 4가지 파형의 미세전류를 각각 적용하여 손상된 인지능력에 미치는 미세전류의 영향을 검토하였다. AD 마우스의 공간 및 물체 인지능력을 확인하기 위해 행동실험을 실시한 결과, novel object recognition test와 Morris water maze test에서 $A{\beta}$로 인해 손상되었던 인지능력이 미세전류 적용군에서 유의적으로 개선됨을 확인하였으며, 지질과산화 반응으로 인한 malondialdehyde의 뇌 내 생성량 또한 감소하였다. 뇌 조직에서 AD 관련 단백질 발현을 측정한 결과, 특히 미세전류 Wave4 [STEP FORM 파형(0, 1.5, 3, 5V), 중첩Hz 적용] 적용군에서 $A{\beta}$ 생성 관련 단백질인 ${\beta}$-secretase, presenilin 1, presenilin 2의 발현이 감소하였고 신경영양인자인 brain-derived neurotrophic factor 단백질 발현이 증가하였다. 이 결과를 바탕으로 AD 마우스에서 미세전류를 이용한 손상된 인지능력에 대한 개선 효과를 확인하였으며, AD 예방 및 치료를 위한 비약물적인 방법으로서 적용할 수 있을 것으로 기대된다.

Keywords

SHGSCZ_2019_v20n5_241_f0001.png 이미지

Fig. 1. Time schedules of application of microcurrent and behavioral tests in Alzheimer’s disease mice model.

SHGSCZ_2019_v20n5_241_f0002.png 이미지

Fig. 2. T-maze test. During the training session, the only one arm is opened that is specified by the experimenter. After 24 h, both arm are opened and the mouse is required to choose between two arms.

SHGSCZ_2019_v20n5_241_f0003.png 이미지

Fig. 3. Novel object recognition test. During the training session, two identical subjects are exist in the test box. After 24 h, one subject is changed and the mouse is required to choose between two different subjects.

SHGSCZ_2019_v20n5_241_f0004.png 이미지

Fig. 4. Morris water maze test. During the training session, the mouse finds hidden platform that is located in a large round pool of opaque water. In the test session, At the 4th day, tests are carried out.

SHGSCZ_2019_v20n5_241_f0005.png 이미지

Fig. 5. Effect of microcurrent on spatial alternation test in Aβ25-35-injected mice. Values are mean±SD. *The space perceptive abilities for old and new routes are significantly different as determined by Student’s t -test (P <0.05).

SHGSCZ_2019_v20n5_241_f0006.png 이미지

Fig. 6. Effect of microcurrent on novel object recognition test in Aβ25-35-injected mice. Values are mean±SD. *The perceptive abilities for familiar and novel object are significantly different as determined by Student’s t -test (P <0.05)

SHGSCZ_2019_v20n5_241_f0007.png 이미지

Fig. 7. Effect of microcurrent on spatial learning memory impairment in Morris water maze test in Aβ25-35-injected mice. Values are mean±SD.

SHGSCZ_2019_v20n5_241_f0008.png 이미지

Fig. 8. Effects of microcurrent on latency to reach the hidden (A) and exposed (B) platform in the Morris water maze test on the final test day in Aβ25-35-injected mice. Values are mean±SD. ##P <0.005 compared to normal group. NS: No significance.

SHGSCZ_2019_v20n5_241_f0009.png 이미지

Fig. 9. Effect of microcurrent on lipid peroxidation in Aβ25-35-injected mice. Values are mean±SD. ###P <0.001 compared to normal group; **P<0.01, ***P<0.001 compared to control group.

SHGSCZ_2019_v20n5_241_f0010.png 이미지

Fig. 10. Effect of microcurrent on the protein levels of BACE, PS1, and PS2 in the brain of Aβ25-35-injected mice. Values are mean±SD.D. ###P <0.001 compared to normal group; ***P <0.001 compared to control group.

SHGSCZ_2019_v20n5_241_f0011.png 이미지

Fig. 11. Effect of microcurrent on the protein levels of BDNF in the brain of Aβ25-35-injected mice. Values are mean±SD. ###P <0.001 compared to normal group; **P <0.01, ***P <0.001 compared to control group.

References

  1. M. Citron. "Alzheimer's disease: strategies for disease modification", Nature Reviews Drug Discovery , Vol.9, No.5, pp.387-398, 2010. DOI: https://doi.org/10.1038/nrd2896
  2. M. J. Cho. "The prevalence and risk factors of dementia in the Korean elderly", Health Welfare Policy Forum. Vol.156, pp.43-48, 2009.
  3. M. S. Parihar, T. Hemnani. "Alzheimer's disease pathogenesis and therapeutic interventions", Journal of Clinical Neuroscience, Vol.11, No.5, pp. 456-467, 2004. DOI: https://doi.org/10.1016/j.jocn.2003.12.007
  4. D. J. Selkoe, J. Hardy. "The amyloid hypothesis of Alzheimer's disease at 25 years", EMBO Molecular Medicine, Vol.8, No.6, pp.595-608, 2016. DOI: https://doi.org/10.15252/emmm.201606210
  5. K. J. Barnham, W. J. McKinstry, G. Multhaup, D. Galatis, C. J. Morton, C. C. Curtain, N. A. Williamson, A. R. White, M. G. Hinds, R. S. Norton, K. Beyreuther, C. L. Masters, M. W. Parker, R. Cappai. "Structure of the Alzheimer's disease amyloid precursor protein copper binding domain. A regulator of neuronal copper homeostasis", Journal of Biological Chemistry, Vol.278, No.19, pp.17401-17407, 2009. DOI: https://doi.org/10.1074/jbc.M300629200
  6. G. F. Chen, T. H. Xu, Y. Yan, Y. R. Zhou, Y. Jiang, K. Melcher, H. E. Xu. "Amyloid beta: structure, biology and structure-based therapeutic development", Acta Pharmacologica Sinica, Vol.38, No.9, pp.1205-1235, 2017. DOI: https://doi.org/10.1038/aps.2017.28
  7. P. B. Watkins, H. J. Zimmerman, M. J. Knapp, S. I. Gracon, K. W. Lewis. "Hepatotoxic effects of tacrine administration in patients with Alzheimer's disease.", Jama, Vol.271, No.13, pp. 992-998, 1994. DOI: https://doi.org/10.1001/jama.1994.03510370044030
  8. J. O. Go. "Effects of self-microcurrent massage on delayed onset muscle soreness (DOMS) and sit and reach: A preliminary study", Journal of Sport and Leisure Studies, Vol.73, pp.463-470, 2018. https://doi.org/10.51979/KSSLS.2018.08.73.463
  9. J. W. Jung "A study on the effect of microcurrent on pain relief" The Journal of Korean Society of Physical Therapy, Vol.12, No.2, pp.195-205, 1991.
  10. H. J. Oh, J. Y. Kim, R. J. Park. "The effects of microcurrent stimulation on recovery of function and pain in chronic low back pain", The Journal of the Korean Society of Physical Medicine, Vol.3 No.1, pp.47-56, 2008.
  11. M. I. Lambert, P. Marcus, T. Burgess, T. D. Noakes. "Electro-membrane microcurrent therapy reduces signs and symptoms of muscle damage", Medicine and Science in Sports and Exercise, Vol.34, No.4, pp.602-607, 2002. DOI: https://doi.org/10.1097/00005768-200204000-00007
  12. C. R. McMakin, W. M. Gregory, T. M. Phillips. "Cytokine changes with microcurrent treatment of fibromyalgia associated with cervical spine trauma", Journal of Bodywork and Movement Therapies, Vol.9, No.3, pp.169-176, 2005. DOI: https://doi.org/10.1016/j.jbmt.2004.12.003
  13. C. Yu, Z. Q. Hu, R. Y. Peng. "Effects and mechanisms of a microcurrent dressing on skin wound healing: a review", Military Medical Research, Vol.1, No.1, pp.24, 2014. DOI: https://doi.org/10.1186/2054-9369-1-24
  14. S. Yennurajalingam, D. H. Kang, W. J. Hwu, N. S. Padhye, C. Masino, S. S. Dibaj, D. D. Liu, J. L. Williams, Z. Lu, E. Bruera. "Cranial electrotherapy stimulation for the management of depression, anxiety, sleep disturbance, and pain in patients with advanced cancer: a preliminary study", Journal of pain and symptom management, Vol.55, No.2, pp.198-206, 2018. DOI: https://doi.org/10.1016/j.jpainsymman.2017.08.027
  15. A. Childs, M. L. Crismon. "The use of cranial electrotherapy stimulation in post-traumatic amnesia: a report of two cases", Brain Injury, Vol.2, No.3, pp.243-247, 1988. DOI: https://doi.org/10.3109/02699058809150948
  16. M. S. Cho. "The effect of microcurrent stimulation on expression of BMP-4 after tibia fracture in rabbits", The Journal of the Korea Contents Association. Vol.7, No.1, pp.1124-1129, 2009. DOI: https://doi.org/10.5392/JKCA.2010.10.3.196
  17. J. S. Kim, K. O. Min, "The effects of microcurrent stimulation on the astrocytes proliferation at injured brain of rabbit", Journal of Korean Physical Therapy Science, Vol.9, No.3, pp.107-119, 2002.
  18. S. U. Kim, J. S. Lee, S. S. Kim, H. D. Shin, S. H. Chung, "The effect of microcurrent electrical neuromuscular stimulation on stress-related hormones", Journal of Rehabilitation Medicine, Vol.13, No.4, pp.1-18, 2003.
  19. R. J. Park, J. S. Kim, I. H. Lee, J. H. Park, D. U. Han, "Effects of electrotherapy on blood velocity of vranial artery in tension - type headache subjects", The Journal of Korean Physical Therapy, Vol.12, No.2, pp.349-359, 2000.
  20. L. L. Baker,S. Rubayi, F. Villar, S. K. Demuth. "Effect of electrical stimulation waveform on healing of ulcers in human beings with spinal cord injury", Wound Repair and Regeneration, Vol.4, No.1, pp.21-28, 1996. DOI: https://doi.org/10.1046/j.1524-475X.1996.40106.x
  21. H. G. Oh, J. H Kim, E. H. Shin, Y. R. Kang, B. G. Lee, S. H. Park, D. I. Moon, I. S. Kwon, Y. P. Kim, M. H. Choi, O. J. Kim, G. H. Park, H. Y. Lee. "Improving effects of platycodon extracts jelly on ${\beta}$-amyloid-induced cytotoxicity and scopolamine-induced cognitive impairment animal models", Korean Journal of Plant Resources, Vol.26, No.4, pp.417-425, 2013. DOI: https://doi.org/10.7732/kjpr.2013.26.4.417
  22. S. Y. Choi, J. Lee, D. G. Lee, S. Lee, E. J. Cho. ""Acer okamotoanum improves cognition and memory function in $A{\beta}_{25-35}$-induced Alzheimer's mice model", Applied Biological Chemistry, Vol.60, No.1, pp.1-9, 2017. DOI: https://doi.org/10.1007/s13765-016-0244-x
  23. K. C. Montgomery. "A test of two explanations of spontaneous alternation", Journal of Comparative and Physiological Psychology, Vol.45, No.3, pp.287-293, 1952. DOI: http://dx.doi.org/10.1037/h0058118
  24. R. A. Bevins, J. Besheer. "Object recognition in rats and mice: a one-trial non-matching-to -sample learning task to study 'recognition memory'", Nature Protocols , Vol.1, No.3, pp.1306-1311, 2006. DOI: https://doi.org/10.1038/nprot.2006.205
  25. R. Morris. "Developments of a water-maze procedure for studying a spatial learning in the rat", Journal of Neuroscience Methods, Vol.11, No.1, pp.47-60, 1984. DOI: https://doi.org/10.1016/0165-0270(84)90007-4
  26. M Mihara, M Uchiyama. "Determination of malonaldehyde precursor in tissues by thiobarbituric acid test", Analytical Biochemistry, Vol.86, No.1, pp.271-278, 1978. DOI: https://doi.org/10.1016/0003-2697(78)90342-1
  27. L. Asth, B. Lobao-Soares, E. Andre, P. Soares Vde, E. C. Gavioli. "The elevated T-maze task as an animal model to simultaneously investigate the effects of drugs on long-term memory and anxiety in mice", Brain Research Bulletin, Vol.87, No.6, pp.526-533, 2012. DOI: https://doi.org/10.1016/j.brainresbull.2012.02.008
  28. D. J. Sanderson, D. M. Bannerman. "The role of habituation in hippocampus-dependent spatial working memory tasks: Evidence from GluA1 AMPA receptor subunit knockout mice", Hippocampus, Vol.22, No.5, pp.981-994, 2012. DOI: https://doi.org/10.1002/hipo.20896
  29. P. A. Dudchenko. "An overview of the tasks used to test working memory in rodents", Neuroscience and Biobehavioral Reviews, Vol.28, No.7, pp.699-709, 2004. DOI: https://doi.org/10.1016/j.neubiorev.2004.09.002
  30. I. M. Mansuy, M. Mayford, B. Jacob, E. R. Kandel, M. E. Bach. "Restricted and regulated overexpression reveals calcineurin as a key component in the transition from short-term to long-term memory", Cell, Vol.92, No.1, pp.39-49, 1998. DOI: https://doi.org/10.1016/S0092-8674(00)80897-1
  31. N. J. Broadbent, L. R. Squire, R. E. Clark. "Spatial memory, recognition memory, and the hippocampus" Proceedings of the National Academy of Sciences, Vol.101, No.40, pp.14515-14520, 2004. DOI: https://doi.org/10.1073/pnas.0406344101
  32. D. M. Bannerman, R. Sprengle, D. J. Sanderson, S. B. McHugh, J, N. Rawlins, H. Monyer, P. H. Seeburg. "Hippocampal synaptic plasticity, spatial memory and anxiety", Nature Reviews Neuroscience, Vol.15, No.3, pp.181-192, 2014. DOI: https://doi.org/10.1038/nrn3677
  33. M. S. George, Z. Nahas, J. J. Borckardt, B. Anderson, M .J. Foust, C. Burns, E. B. Short "Brain stimulation for the treatment of psychiatric disorders", Current opinion in psychiatry, Vol.20, No.3, pp.250-254, 2007. DOI: https://doi.org/10.1097/YCO.0b013e3280ad4698
  34. J. D. Feusner, S. Madsen, T. D. Moody, C. Bohon, E. Hembacher, S. Y. Bookheimer, A. Bystritsky "Effects of cranial electrotherapy stimulation on resting state brain activity", Brain and behavior , Vol.2, No.3, pp.211-220, 2012. DOI: https://doi.org/10.1002/brb3.45
  35. R. B. Smith. "Microcurrent therapies: emerging theories of physiological information processing", NeuroRehabilitation, Vol.17, No.1, pp.3-7, 2002. https://doi.org/10.3233/NRE-2002-17102
  36. Y. H. Kwon, C. S. Kim, S. H. Jang. "Cortical activation in the human brain induced by transcranial direct current stimulation", The Journal of Korean Physical Therapy, Vol.21, No.4, pp.73-79, 2009.
  37. W. R. Markesbery, J. M. Carney. "Oxidative alterations in Alzheimer's disease", Brain Pathology, Vol.9, No.1, pp.133-146, 1999. DOI: https://doi.org/10.1111/j.1750-3639.1999.tb00215.x
  38. N. A. Avdulov, S. V. Chochina, U. Igbavboa, E. O. O'Hare, F. Schroeder, J. P. Cleary, W. G. Wood. "Amyloid beta-peptides increase annular and bulk fluidity and induce lipid peroxidation in brain synaptic plasma membranes", Journal of Neurochemistry, Vol.68, No.5, pp.2086-2091, 1997. DOI: https://doi.org/10.1046/j.1471-4159.1997.68052086.x
  39. D. A. Butterfield, C. M. Lauderback. "Lipid peroxidation and protein oxidation in Alzheimer's disease brain: potential causes and consequences involving amyloid ${\beta}$-peptide-associated free radical oxidative stress", Free Radical Biology and Medicine, Vol.32, pp.1050- 1060, 2002. DOI: https://doi.org/10.1016/S0891-5849(02)00794-3
  40. Y. Zhang, H. Xu. "Molecular and cellular mechanisms for Alzheimer's disease: understanding APP metabolism", Current Molecular Medicine, Vol.7, pp.687-696, 2007. DOI: https://doi.org/10.2174/156652407782564462
  41. V. Echeverria, D. E. Berman, O. Arancio. "Oligomers of ${\beta}$-amyloid peptide inhibit BDNF-induced Arc expression in cultured cortical neurons", Current Alzheimer Research, Vol.4, pp.518-521, 2007. DOI: https://doi.org/10.2174/156720507783018190
  42. I. Opris, V. P. Ferrera. "Modifying cognition and behavior with electrical microstimulation: implications for cognitive prostheses", Neuroscience and Biobehavioral Review, Vol.47, pp.321-35, 2014. DOI: https://doi.org/10.1016/j.neubiorev.2014.09.003
  43. I. Opris. "Electrical Stimulation for Modification of Memory and Cognition", Electroceuticals, pp. 283- 316, 2017. DOI: https://doi.org/10.1007/978-3-319-28612-9_12
  44. T. A. Ukhanova, F. E. Gorbunov. "Micro-current reflexotherapy in the rehabilitative treatment of the speech function disorders in children with cerebral palsy", Voprosy kurortologii, fizioterapii, i lechebnoi fizicheskoi kultury, Vol.1, pp.3-6, 2011.
  45. S. Liss, B. Liss. "Physiological and therapeutic effects of high frequency electrical pulses", Integrative Physiological and Behavioral Science, Vol.31, No.2, pp.88-95, 1996. DOI: https://doi.org/10.1007/BF02699781