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Cognitive-enhancing Effects of a Fermented Milk Product, LHFM on Scopolamine-induced Amnesia

발효유 산물인 LHFM의 인지기능 개선 효과

  • Jeon, Yong-Jin (LDONG Research Laboratories, ILDONG Pharmaceutical Co. Ltd.) ;
  • Kim, Jun-Hyeong (LDONG Research Laboratories, ILDONG Pharmaceutical Co. Ltd.) ;
  • Lee, Myong-Jae (LDONG Research Laboratories, ILDONG Pharmaceutical Co. Ltd.) ;
  • Jeon, Woo-Jin (LDONG Research Laboratories, ILDONG Pharmaceutical Co. Ltd.) ;
  • Lee, Seung-Hun (LDONG Research Laboratories, ILDONG Pharmaceutical Co. Ltd.) ;
  • Yeon, Seung-Woo (LDONG Research Laboratories, ILDONG Pharmaceutical Co. Ltd.) ;
  • Kang, Jae-Hoon (LDONG Research Laboratories, ILDONG Pharmaceutical Co. Ltd.)
  • Received : 2012.01.12
  • Accepted : 2012.07.05
  • Published : 2012.08.31

Abstract

Probiotics and their products, such as yogurt and cheese have been widely consumed in many countries with proven health benefits including anti-microbial activity and anti-diarrheal activity. LHFM (Lactobacillus helveticus - fermented milk) is a processed skim milk powder, fermented by a probiotics, L. helveticus IDCC3801. In the present study, we aimed to investigate the neuroprotective effects and the cognitive improvements of LHFM. LHFM itself did not show any cytotoxicity to the human neuroblastoma cell line, SH-SY5Y; however, it dose-dependently protected against glutamate-induced neuronal cell death. LHFM also attenuated scopolamine-induced memory deficit in Y-maze and Morris-water maze. In the analysis of hippocampus after a behavior test, LHFM significantly increased the acetylcholine level and also inhibited acetylcholine esterase activity. Therefore, the raised acetylcholine release partially contributes to the improvement of learning and memory by a treatment with LHFM. These results suggest that LHFM is an effective material for prevention or improvement of cognitive impairments caused by neuronal cell damage and central cholinergic dysfunction.

본 연구팀의 선행 연구 결과, L. helveticus IDCC3801의 발효유 주정 침전물이 BACE의 활성 억제를 통한 amyloid beta($A{\beta}$) 생성 저해효과를 갖고 있음을 확인하였다(15). 이러한 결과를 바탕으로 L. helveticus IDCC3801의 발효유 주정 침전물의 산업화를 위한 공정 개선연구를 진행하였고, 대량생산을 통해 LHFM을 확보하였다. 본 연구는 LHFM의 인지기능 개선 기능성 입증 연구로써 $A{\beta}$ 저해효과 외에 신경세포 보호효과 및 기억력 개선 효능을 확인하고 어떠한 작용 기전으로 개선 효과가 나타나는지 조사한 것으로 scopolamine으로 기억 손상을 유발한 mouse에서 학습 능력과 기억력 개선 효과, 신경세포 보호 효과, AChE 저해와 ACh 증가 효과 등을 평가하였다. LHFM은 신경세포 사멸을 유도하는 고농도의 glutamate가 존재하는 환경에서 농도 의존적으로 신경세포의 사멸을 억제하여 신경세포를 보호하였다. 또한 LHFM은 in vitro에서 농도 의존적으로 강력하게 AChE의 활성을 저해하였다. 이러한 in vitro 결과들을 근거로 scopolamine으로 기억 손상을 유발한 mouse에서 Morris water maze와 Y-maze 행동 시험을 통해 LHFM의 학습능력과 기억 개선 효과를 조사하였다. LHFM은 Morris water maze에서 실험 2일째부터 escape latency시간을 유의적으로 감소 시켰으며 5일째에서는 정상 mouse와 동등한 수준으로 감소되어 우수한 학습 효과를 보였다. 실험 6일째 platform을 치운 후 시행한 probe trial에서도 platform이 있던 위치에 머무는 회수가 scopolamine을 단독으로 처리한 것보다 유의적으로 높아 장기기억의 개선에도 효과가 있었다. Y-maze 시험에서도 LHFM은 scopolamine 단독 처리군과 비교하여 뚜렷하게 변경 행동력을 증가시켜 여러 행동 시험을 통해 LHFM의 인지기능 개선 효과를 확인하였다. 행동실험 후 hippocampus를 적출하여 ACh 및 AChE의 활성을 측정한 결과, donepezil과 마찬가지로 LHFM은 AChE의 활성을 유의적으로 억제하였으며 또한 ACh 함량도 증가시켰다. 결론적으로 LHFM은 신경세포 보호 효과와 신경전달물질인 ACh의 뇌 조직 내 농도를 높여 인지기능 개선 효과를 보이는 것을 확인하였다.

Keywords

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