Fucoidan Ameliorates Scopolamine-induced Neuronal Impairment and Memory Dysfunction in Rats via Activation of Cholinergic System and Regulation of cAMP-response Element-binding Protein and Brain-derived Neurotrophic Factor Expressions Bombi Lee · Bongjun Sur · Jinhee Park · Heungsop Shin · Sunoh Kwon · Mijung Yeom · Seok Joong Kim · Kyungsoo Kim · Insop Shim · Chang Shik Yin · Hyejung Lee · Dae-Hyun Hahm Received: 21 June 2012 / Accepted: 26 September 2012 / Published Online: 31 December 2012 © The Korean Society for Applied Biological Chemistry and Springer 2012 Abstract Effect of fucoidan (FCN) treatment on improving memory defects caused by administration of scopolamine (SCO) to the rats was examined. The effects of FCN on the acetylcholinergic system as well as the expression of cAMP-response element- binding protein (CREB) and brain-derived neurotrophic factor (BDNF) mRNAs in the hippocampus were also investigated. Male rats were administered daily doses for 14 days of FCN (10, 20, and 50 mg/kg, i.p.) 30 min before scopolamine injection (2 mg/kg, i.p.). Daily administration of FCN improved memory impairment as measured by the passive avoidance test (PAT) and reduced the escape latency for finding the platform in the Morris water maze (MWM) test. Administration of FCN significantly alleviated memory-associated decreases in cholinergic immuno- reactivity and restored the expression level of BDNF and CREB mRNAs in the hippocampus. Additionally, FCN significantly decreased the expression of pro-inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) mRNAs in the hippocampus. These results demonstrated that FCN has significant neuroprotective effects against neuronal impairment and memory dysfunction caused by scopolamine in rats. Thus, these findings suggest that FCN is useful as a therapeutic agent for improving cognitive functioning via stimulation of cholinergic enzyme activities and regulation of CREB and BDNF expressions in the brain. Keywords brain-derived neurotrophic factor · cAMP-response element-binding protein · cholinergic neurons · memory · scopolamine Introduction Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by irreversible, progressive loss in cognitive functioning due to degeneration of the cholinergic nervous system and neuronal dysfunction (Scarpini et al., 2003). In regards to neuropathological features of memory loss and cognitive dysfunction, as observed primarily in patients with AD, cholinergic deficits and neuronal dysfunction have been considered as the primary causes (Hasselmo, 2006). Accordingly, B. Lee · S. Kwon · M. Yeom · I. Shim · C. S. Yin · H. Lee · D.-H. Hahm () Acupuncture and Meridian Science Research Center, College of Oriental Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea E-mail: dhhahm@khu.ac.kr; dhahm@paran.com B. Sur · J. Park · I. Shim · C. S. Yin · H. Lee · D.-H. Hahm The Graduate School of Basic Science of Oriental Medicine, College of Oriental Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea H. Shin Department of Chemical Engineering and Biotechnology, Korea Polytechnic University, Kyonggi-do, 429-793, Republic of Korea S. J. Kim Department of Food and Nutrition, College of Natural science, Dongduk Women’s University, Seoul 136-714, Republic of Korea K. Kim East-West Bone and Joint Research Institute, Kyung Hee University, Seoul 134-727, Republic of Korea ORIGINAL ARTICLE J Korean Soc Appl Biol Chem (2012) 55, 711-720 DOI 10.1007/s13765-012-2137-y