Sulforaphane prevents cholinergic deficits and cognitive impairment in mice

1. 3rd World Congress on Pharmacology Birmingham, UK 2016. 08. 09 Sulforaphane prevents cholinergic deficits and cognitive impairment in mice Jiyoung Kim, PhD Seoul National University

2. Preventive Medicine

3. Science 2012 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.

4. c Scientific American Mind 2016 March/April

5. 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.

6. 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

7. 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)

8. 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.

9. Sulforaphane Inhibits Scopolamine-Induced Memory Impairment c Kim J et al. Pharm Res, 2014

10. Sulforaphane Protects Cholinergic System Kim J et al. Pharm Res, 2014

11. 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.

12. Kim J et al. Pharm Res, 2014

13. 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 Amyloid β Amyloid β Amyloid β pTau Amyloid β GAPDH

14. Triple Transgenic (APP-PS1-Tau)Alzheimer’s Disease Mouse Model

15. 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 MAP2(Green)-positive primary cortical neurons cultured by Jiyoung Kim