title: Neuroprotective effects of sulforaphane on cholinergic neurons in mice with Alzheimer's disease-like lesions.
abstract: Alzheimer's disease (AD) is a common neurodegenerative disease in elderly individuals, and effective therapies are unavailable. This study was designed to investigate the neuroprotective effects of sulforaphane (an activator of NF-E2-related factor 2) on mice with AD-like lesions induced by combined administration of aluminum and D-galactose. Step-down-type passive avoidance tests showed sulforaphane ameliorated cognitive impairment in AD-like mice. Immunohistochemistry results indicated sulforaphane attenuated cholinergic neuron loss in the medial septal and hippocampal CA1 regions in AD-like mice. However, spectrophotometry revealed no significant difference in acetylcholine level or the activity of choline acetyltransferase or acetylcholinesterase in the cerebral cortex among groups of control and AD-like mice with and without sulforaphane treatment. Sulforaphane significantly increased the numbers of 5-bromo-2'-deoxyuridine-positive neurons in the subventricular and subgranular zones in AD-like mice which were significantly augmented compared with controls. Atomic absorption spectrometry revealed significantly lower aluminum levels in the brains of sulforaphane-treated AD-like mice than in those that did not receive sulforaphane treatment. In conclusion, sulforaphane ameliorates neurobehavioral deficits by reducing cholinergic neuron loss in the brains of AD-like mice, and the mechanism may be associated with neurogenesis and aluminum load reduction. These findings suggest that phytochemical sulforaphane has potential application in AD therapeutics.
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, Shenyang 110001, China. z_zhangrui@163.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, Shenyang 110001, China. zhangjz0107@163.com.
authors.forename: Jingzhu
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, Shenyang 110001, China. fanglingduo@163.com.
authors.forename: Lingduo
authors.initials: L
authors.lastname: Fang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, Shenyang 110001, China. rabbitto89@163.com.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, Shenyang 110001, China. yuezhao2000@163.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Clinical Nutrition, First Affiliated Hospital, China Medical University, Heping District, Shenyang 110001, China. shiwanying2019@gmail.com.
authors.forename: Wanying
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, Shenyang 110001, China. anli@mail.cmu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: An
mesh_terms: D000535:Aluminum / Q000633:toxicity; D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D000818:Animals; D001835:Body Weight; D056547:CA1 Region, Hippocampal / Q000166:cytology; D059329:Cholinergic Neurons / Q000187:drug effects*; D005260:Female; D005690:Galactose / Q000633:toxicity; D007150:Immunohistochemistry; D017879:Isothiocyanates / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D013454:Sulfoxides
chemical_list: D017879:Isothiocyanates; D013454:Sulfoxides; D000535:Aluminum; C016766:sulforaphane; D005690:Galactose