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Neuroprotective Effects of Sulforaphane on Cholinergic Neurons in Mice with Alzheimer’s Disease-Like Lesions

by Rui Zhang 1,†, Jingzhu Zhang 1,†, Lingduo Fang 1, Xi Li 1, Yue Zhao 1, Wanying Shi 2 and Li An 1,*
Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, Shenyang 110001, China
Department of Clinical Nutrition, First Affiliated Hospital, China Medical University, Heping District, Shenyang 110001, China
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2014, 15(8), 14396-14410;
Received: 4 July 2014 / Revised: 5 August 2014 / Accepted: 11 August 2014 / Published: 18 August 2014
(This article belongs to the Section Biochemistry)
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. View Full-Text
Keywords: Alzheimer’s disease; sulforaphane; neurobehavior; cholinergic neuron Alzheimer’s disease; sulforaphane; neurobehavior; cholinergic neuron
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Zhang, R.; Zhang, J.; Fang, L.; Li, X.; Zhao, Y.; Shi, W.; An, L. Neuroprotective Effects of Sulforaphane on Cholinergic Neurons in Mice with Alzheimer’s Disease-Like Lesions. Int. J. Mol. Sci. 2014, 15, 14396-14410.

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