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

  • 제20권5호
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  • Pages.241-251
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  • 2019
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  • 1975-4701(pISSN)
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  • 2288-4688(eISSN)
한국산학기술학회 (The Korea Academia-Industrial cooperation Society)
권호 표지
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알츠하이머 질환 마우스에서 중첩주파수를 활용한 미세전류가 인지능력 개선에 미치는 효과

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

  • 김민정 (부산대학교 식품영양학과) ;
  • 이아영 (경남과학기술대학교 식품과학부) ;
  • 조동식 ((주)내츄럴웰테크) ;
  • 조은주 (부산대학교 식품영양학과)
  • 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)
  • 투고 : 2019.02.12
  • 심사 : 2019.05.03
  • 발행 : 2019.05.31
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초록

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.

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.

키워드

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

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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.

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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.

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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.

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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).

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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)

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

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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.

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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.

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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.

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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.

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