Neuroprotective Effects of Icariin on Brain Metabolism, Mitochondrial Functions, and Cognition in Triple‐Transgenic Alzheimer's Disease Mice

CNS Neuroscience and Therapeutics - Tập 22 Số 1 - Trang 63-73 - 2016
Yijing Chen1, Hai‐Yang Zheng1, Xiuxian Huang2, Shuangxue Han1, Dongsheng Zhang2, Jiazuan Ni1, Xiaoyang He1
1College of Life Science, Shenzhen Key Laboratory of Marine Bioresources and Ecology, Shenzhen University, Shenzhen, China
2College of Life Science, Shenzhen Key Laboratory of Microbial Genetic Engineering, Shenzhen University, Shenzhen, China

Tóm tắt

SummaryAimsThis study investigated the neuroprotective properties of icariin (an effective component of traditional Chinese herbal medicine Epimedium) on neuronal function and brain energy metabolism maintenance in a triple‐transgenic mouse model of Alzheimer's disease (3 × Tg‐AD).Methods3 × Tg‐AD mice as well as primary neurons were subjected to icariin treatment. Morris water maze assay, magnetic resonance spectroscopy (MRS), Western blotting, ELISA, and immunohistochemistry analysis were used to evaluate the effects of icariin administration.ResultsIcariin significantly improved spatial learning and memory retention in 3 × Tg‐AD mice, promoted neuronal cell activity as identified by the enhancement of brain metabolite N‐acetylaspartate level and ATP production in AD mice, preserved the expressions of mitochondrial key enzymes COX IV, PDHE1α, and synaptic protein PSD95, reduced Aβ plaque deposition in the cortex and hippocampus of AD mice, and inhibited β‐site APP cleavage enzyme 1 (BACE1) expression. Icariin treatment also decreased the levels of extracellular and intracellular Aβ1‐42 in 3 × Tg‐AD primary neurons, modulated the distribution of Aβ along the neurites, and protected against mitochondrial fragmentation in 3 × Tg‐AD neurons.ConclusionsIcariin shows neuroprotective effects in 3 × Tg‐AD mice and may be a promising multitarget drug in the prevention/protection against AD.

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Tài liệu tham khảo

10.1016/S0896-6273(03)00434-3

10.1523/JNEUROSCI.6142-10.2011

10.1152/physrev.2001.81.2.741

10.1073/pnas.1006586107

10.1016/j.bbadis.2013.09.010

10.1523/JNEUROSCI.1357-09.2009

10.1073/pnas.0903563106

10.1073/pnas.0308512100

10.1111/j.1749-6632.2000.tb06370.x

10.1212/WNL.57.2.260

10.1016/0304-3940(80)90220-7

10.3233/JAD-2010-100129

10.1016/j.pneurobio.2006.12.003

10.1016/j.neurobiolaging.2006.06.018

10.1016/j.jns.2013.08.023

10.3233/JAD-2011-110254

10.1089/08977150151070856

10.1007/s004150170052

10.1016/j.jep.2011.01.001

10.1016/j.ejphar.2009.09.039

10.1002/ptr.3183

10.1016/j.neuropharm.2010.07.020

10.7150/ijbs.6232

10.1016/0165-0270(84)90007-4

10.1038/nprot.2006.116

Yu J, 2015, Identification of the key molecules involved in chronic copper exposure‐aggravated memory impairment in transgenic mice of Alzheimer's disease using proteomic analysis, J Alzheimers Dis, 44, 455, 10.3233/JAD-141776

10.1016/j.neuron.2005.01.040

10.1016/j.nbd.2007.06.013

10.1089/08977150152693683

10.1371/journal.pone.0017397

10.1016/j.neuron.2004.08.013

10.1016/S0006-8993(01)03294-2

10.1038/nn.3028

10.1097/00001756-199605310-00014

Kantarci K, 2003, Proton MR spectroscopy in mild cognitive impairment and Alzheimer disease: Comparison of 1.5 and 3 T, AJNR Am J Neuroradiol, 24, 843

10.1089/neu.2004.21.1154

10.1212/WNL.0b013e3181a60a20

Zimny A, 2014, Evaluation of the posterior cingulate region with FDG‐PET and advanced MR techniques in patients with amnestic mild cognitive impairment: Comparison of the methods, J Alzheimers Dis, 44, 329, 10.3233/JAD-132138

10.1111/j.1440-1681.2007.04647.x

10.1016/j.bbabio.2014.02.007

10.1016/j.bbadis.2011.01.007

10.1155/2012/843649

10.1523/JNEUROSCI.1836-13.2013

10.1126/science.1091230

10.1016/j.molmed.2007.12.002

10.1016/j.yfrne.2013.08.001

10.3233/JAD-2010-100339

10.1096/fj.04-2582fje

10.1016/j.mam.2011.10.005

10.1016/j.fct.2012.05.017

10.1523/JNEUROSCI.4391-07.2007

10.1016/j.neurobiolaging.2011.03.001

10.1210/en.2012-1464

10.1016/j.neurobiolaging.2009.12.010

10.1016/j.pbb.2010.05.021

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CNS Neuroscience and Therapeutics

Tập 22 Số 1

63-73

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