Jiyoung Kim, PhD Seoul National University 3rd World Congress on Pharmacology Birmingham, UK 2016. 08. 09 Sulforaphane prevents cholinergic deficits and cognitive impairment in mice Hello, everyone. It is a pleasure to be here with all of you today. Having the opportunity to do this presentation is indeed an honor. I hope that I become a strong candidate for the position which your college is looking for. I hope that I will have the opportunity to develop my research further at your university in the coming years. Moreover, I would like to contribute to the research at the college of pharmacy, Korea University so that the program as well as the student in this program become more advanced to promote the knowledge of this field throughout the world, making a meaningful and lasting change. There was evidence… Jiyoung Kim, PhD Seoul National University

Preventive Medicine The quotation advices us that preventing diseases is important / The quotation advices us that the prevention of diseases is important How important prevention is… Before the disease occurs…

Science 2012 How important prevention is… Despite intensive laboratory and clinical research over three decades, an effective treatment to delay the onset and progression of Alzheimer's disease is not at hand. Recent clinical trial failures suggest that we must treat the disease earlier than in its mild to moderate stages.

c Scientific American Mind 2016 March/April

Cruciferous Vegetables: Plants Containing Sulforaphane Sulforaphane is an organosulfur compound found in cruciferous plants broccoli sprouts broccoli purple cabbages cabbages brussels sprouts cauliflower kohlrabi bok choy kale etc.

Anti-Dementia Effects of Sulforaphane Sulforaphane (1-isothiocyanato-4-methylsulfinylbutane) - a strong Nrf2 activity inducer - first attracted interest because of its potential anti-cancer activity - recent in vitro and in vivo studies have examined the potential neuroprotective actions the potential effects of sulforaphane on cognitive function have not yet been elucidated

Scopolamine-Induced Memory Impairment Animal Model Scopolamine-Induced Memory Impairment c Alzheimer’s disease - Muscarinic cholinergic receptor ↓ - Acetylcholine ↓ Scopolamine - Muscarinic cholinergic blockade - Acetylcholinesterase activity ↑ - Cholinergic hypofunction Scopolamine has been used as a standard / reference drug for inducing cognitive deficits in healthy humans and animals (Bartus RT et al. Science, 1982) Scopolamine 동물실험 모델 - 일시적 기억장애를 일으키는 물질인 scopolamine (muscarinic antagonist)을 이용하여 일시적 장애를 일으킨 후 시험하고자 하는 sample이 효능이 있는지 여부를 확인하는 실험모델

Behavioral test - Water maze test Start Start Start Start The water maze is commonly used to assay spatial cognition, or, more generally, learning and memory in experimental rodent models. Spatial learning is then typically assessed in a probe test, where the platform is removed from the pool and the mouse or rat is allowed to search for it.

Sulforaphane Inhibits Scopolamine-Induced Memory Impairment Kim J et al. Pharm Res, 2014 How long it takes to find the platform… We measured the distance traveled … still takes a long time…

Sulforaphane Protects Cholinergic System Kim J et al. Pharm Res, 2014 … keeps the level of … high.

Sulforaphane Inhibits Acetylcholinesterase Activity Cell-free effect of sulforaphane on acetylcholinesterase (AChE) activity. Percentage of AChE activity inhibition by sulforaphane (SFN, 0, 1.25, 2.5, 5, 10, 20, 40,80, 160, 320, or 640 mM). Data are presented as mean ± SEM (n = 6). The IC50 value was calculated by means of regression analysis.

Kim J et al. Pharm Res, 2014

Triple Transgenic (APP-PS1-Tau) Alzheimer’s Disease Mouse Model WT 3XTg 17 M 10 M 15 M pTau pTau pTau WT 3Xtg 11 M 17 M 10 M 15 M APP Scopolamine 동물실험 모델 - 일시적 기억장애를 일으키는 물질인 scopolamine (muscarinic antagonist)을 이용하여 일시적 장애를 일으킨 후 시험하고자 하는 sample이 효능이 있는지 여부를 확인하는 실험모델 Amyloid β Amyloid β Amyloid β pTau Amyloid β GAPDH

Triple Transgenic (APP-PS1-Tau) Alzheimer’s Disease Mouse Model These mouse have the learning and memory deficits at the age of 6 month.

Acknowledgements Graduate Students Siyoung Lee Jisung Kim Seoul National University Prof. Ki Won Lee Konkuk University Bo-Ryoung Choi Prof. Jung-Soo Han Grant NRF-2012R1A1A3011954 NRF-2015R1A1A3A04000963 Thank you for your attention. If you have any questions or comments, please feel free to share them with me. MAP2(Green)-positive primary cortical neurons cultured by Jiyoung Kim