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

CNS Neuroscience and Therapeutics

Volumn 22, Issue 1, 2016, Pages 63-73

  Chen, Yi Jing ^a   Zheng, Hai Yang ^a   Huang, Xiu Xian ^a   Han, Shuang Xue ^a   Zhang, Dong Sheng ^a   Ni, Jia Zuan ^a   He, Xiao Yang ^a  

^a SHENZHEN UNIVERSITY   (China)

Author keywords

Alzheimer's disease; Icariin; Magnetic resonance spectroscopy; Mitochondrial dysfunction; N acetylaspartate

Indexed keywords

ADENOSINE TRIPHOSPHATE; AMYLOID BETA PROTEIN; AMYLOID BETA PROTEIN[1-42]; BETA SECRETASE 1; ICARIIN; POSTSYNAPTIC DENSITY PROTEIN 95; PROSTAGLANDIN SYNTHASE; AMYLOID PRECURSOR PROTEIN; APP PROTEIN, HUMAN; FLAVONOID; MAPT PROTEIN, HUMAN; NEUROPROTECTIVE AGENT; PRESENILIN 1; PSEN1 PROTEIN, HUMAN; TAU PROTEIN;

ALZHEIMER DISEASE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN CORTEX; BRAIN METABOLISM; BRAIN NERVE CELL; COGNITION; CONTROLLED STUDY; DRUG EFFECT; ENERGY METABOLISM; ENZYME LINKED IMMUNOSORBENT ASSAY; EPIMEDIUM; FEMALE; HIPPOCAMPUS; IMMUNOHISTOCHEMISTRY; MEMORY CONSOLIDATION; MITOCHONDRION; MORRIS WATER MAZE TEST; MOUSE; NEUROPROTECTION; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; SPATIAL LEARNING; TRANSGENIC MOUSE; WESTERN BLOTTING; ANIMAL; BRAIN; CELL CULTURE; DISEASE MODEL; DRUG EFFECTS; GENETICS; HUMAN; MAZE TEST; METABOLISM; NERVE CELL; PATHOLOGY; PHYSIOLOGY; PRECLINICAL STUDY; PSYCHOLOGY; SPATIAL MEMORY;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN PRECURSOR; ANIMALS; BRAIN; CELLS, CULTURED; COGNITION; DISEASE MODELS, ANIMAL; DRUG EVALUATION, PRECLINICAL; FEMALE; FLAVONOIDS; HUMANS; MAZE LEARNING; MICE, TRANSGENIC; MITOCHONDRIA; NEURONS; NEUROPROTECTIVE AGENTS; PRESENILIN-1; SPATIAL MEMORY; TAU PROTEINS;

EID: 84955183280     PISSN: 17555930     EISSN: 17555949     Source Type: Journal    
DOI: 10.1111/cns.12473     Document Type: Article

References (55)

1. Oddo S, Caccamo A, Shepherd JD, et al. Triple-transgenic model of Alzheimer's disease with plaques and tangles: Intracellular Abeta and synaptic dysfunction. Neuron 2003;39:409-421.
2. Perez-Cruz C, Nolte MW, van Gaalen MM, et al. Reduced spine density in specific regions of CA1 pyramidal neurons in two transgenic mouse models of Alzheimer's disease. J Neurosci 2011;31:3926-3934.
3. Selkoe DJ. Alzheimer's disease: Genes, proteins, and therapy. Physiol Rev 2001;81:741-766.
4. Du H, Guo L, Yan S, Sosunov AA, McKhann GM, Yan SS. Early deficits in synaptic mitochondria in an Alzheimer's disease mouse model. Proc Natl Acad Sci U S A 2010;107:18670-18675.
5. Swerdlow RH, Burns JM, Khan SM. The Alzheimer's disease mitochondrial cascade hypothesis: Progress and perspectives. Biochim Biophys Acta 2014;1842:1219-1231.
6. Wang X, Su B, Lee HG, et al. Impaired balance of mitochondrial fission and fusion in Alzheimer's disease. J Neurosci 2009;29:9090-9103.
7. Yao J, Irwin RW, Zhao L, Nilsen J, Hamilton RT, Brinton RD. Mitochondrial bioenergetic deficit precedes Alzheimer's pathology in female mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A 2009;106:14670-14675.
8. Blalock EM, Geddes JW, Chen KC, Porter NM, Markesbery WR, Landfield PW. Incipient Alzheimer's disease: Microarray correlation analyses reveal major transcriptional and tumor suppressor responses. Proc Natl Acad Sci U S A 2004;101:2173-2178.
9. Blass JP, Sheu RK, Gibson GE. Inherent abnormalities in energy metabolism in Alzheimer disease. Interaction with cerebrovascular compromise. Ann N Y Acad Sci 2000;903:204-221.
10. Cottrell DA, Blakely EL, Johnson MA, Ince PG, Turnbull DM. Mitochondrial enzyme-deficient hippocampal neurons and choroidal cells in AD. Neurology 2001;57:260-264.
11. Perry EK, Perry RH, Tomlinson BE, Blessed G, Gibson PH. Coenzyme A-acetylating enzymes in Alzheimer's disease: Possible cholinergic 'compartment' of pyruvate dehydrogenase. Neurosci Lett 1980;18:105-110.
12. Valla J, Yaari R, Wolf AB, et al. Reduced posterior cingulate mitochondrial activity in expired young adult carriers of the APOE epsilon4 allele, the major late-onset Alzheimer's susceptibility gene. J Alzheimers Dis 2010;22:307-313.
13. Moffett JR, Ross B, Arun P, Madhavarao CN, Namboodiri AM. N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology. Prog Neurobiol 2007;81:89-131.
14. Kantarci K, Weigand SD, Petersen RC, et al. Longitudinal 1H MRS changes in mild cognitive impairment and Alzheimer's disease. Neurobiol Aging 2007;28:1330-1339.
15. Targosz-Gajniak MG, Siuda JS, Wicher MM, et al. Magnetic resonance spectroscopy as a predictor of conversion of mild cognitive impairment to dementia. J Neurol Sci 2013;335:58-63.
16. Zimny A, Szewczyk P, Trypka E, et al. Multimodal imaging in diagnosis of Alzheimer's disease and amnestic mild cognitive impairment: Value of magnetic resonance spectroscopy, perfusion, and diffusion tensor imaging of the posterior cingulate region. J Alzheimers Dis 2011;27:591-601.
17. Gasparovic C, Arfai N, Smid N, Feeney DM. Decrease and recovery of N-acetylaspartate/creatine in rat brain remote from focal injury. J Neurotrauma 2001;18:241-246.
18. Narayanan S, De Stefano N, Francis GS, et al. Axonal metabolic recovery in multiple sclerosis patients treated with interferon beta-1b. J Neurol 2001;248:979-986.
19. Ma H, He X, Yang Y, Li M, Hao D, Jia Z. The genus Epimedium: An ethnopharmacological and phytochemical review. J Ethnopharmacol 2011;134:519-541.
20. Nie J, Luo Y, Huang XN, Gong QH, Wu Q, Shi JS. Icariin inhibits beta-amyloid peptide segment 25-35 induced expression of beta-secretase in rat hippocampus. Eur J Pharmacol 2010;626:213-218.
21. Urano T, Tohda C. Icariin improves memory impairment in Alzheimer's disease model mice (5xFAD) and attenuates amyloid beta-induced neurite atrophy. Phytother Res 2010;24:1658-1663.
22. Zeng KW, Ko H, Yang HO, Wang XM. Icariin attenuates beta-amyloid-induced neurotoxicity by inhibition of tau protein hyperphosphorylation in PC12 cells. Neuropharmacology 2010;59:542-550.
23. Zhang L, Shen C, Chu J, Zhang R, Li Y, Li L. Icariin decreases the expression of APP and BACE-1 and reduces the beta-amyloid burden in an APP transgenic mouse model of Alzheimer's disease. Int J Biol Sci 2014;10:181-191.
24. Morris R. Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 1984;11:47-60.
25. Vorhees CV, Williams MT. Morris water maze: Procedures for assessing spatial and related forms of learning and memory. Nat Protoc 2006;1:848-858.
26. Yu J, Luo X, Xu H, et al. 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 2015;44:455-469.
27. Billings LM, Oddo S, Green KN, McGaugh JL, LaFerla FM. Intraneuronal Abeta causes the onset of early Alzheimer's disease-related cognitive deficits in transgenic mice. Neuron 2005;45:675-688.
28. Clinton LK, Billings LM, Green KN, et al. Age-dependent sexual dimorphism in cognition and stress response in the 3xTg-AD mice. Neurobiol Dis 2007;28:76-82.
29. Signoretti S, Marmarou A, Tavazzi B, Lazzarino G, Beaumont A, Vagnozzi R. N-Acetylaspartate reduction as a measure of injury severity and mitochondrial dysfunction following diffuse traumatic brain injury. J Neurotrauma 2001;18:977-991.
30. Arsenault D, Julien C, Tremblay C, Calon F. DHA improves cognition and prevents dysfunction of entorhinal cortex neurons in 3xTg-AD mice. PLoS ONE 2011;6:e17397.
31. Calon F, Lim GP, Yang F, et al. Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model. Neuron 2004;43:633-645.
32. King DL, Arendash GW. Maintained synaptophysin immunoreactivity in Tg2576 transgenic mice during aging: Correlations with cognitive impairment. Brain Res 2002;926:58-68.
33. Benilova I, Karran E, De Strooper B. The toxic Abeta oligomer and Alzheimer's disease: An emperor in need of clothes. Nat Neurosci 2012;15:349-357.
34. Bates TE, Strangward M, Keelan J, Davey GP, Munro PM, Clark JB. Inhibition of N-acetylaspartate production: Implications for 1H MRS studies in vivo. NeuroReport 1996;7:1397-1400.
35. Kantarci K, Reynolds G, Petersen RC, et al. Proton MR spectroscopy in mild cognitive impairment and Alzheimer disease: Comparison of 1.5 and 3 T. AJNR Am J Neuroradiol 2003;24:843-849.
36. Signoretti S, Marmarou A, Tavazzi B, et al. The protective effect of cyclosporin A upon N-acetylaspartate and mitochondrial dysfunction following experimental diffuse traumatic brain injury. J Neurotrauma 2004;21:1154-1167.
37. Jessen F, Gur O, Block W, et al. A multicenter (1)H-MRS study of the medial temporal lobe in AD and MCI. Neurology 2009;72:1735-1740.
38. Zimny A, Bladowska J, Macioszek A, et al. 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 2014;44:329-338.
39. Luo Y, Nie J, Gong QH, Lu YF, Wu Q, Shi JS. Protective effects of icariin against learning and memory deficits induced by aluminium in rats. Clin Exp Pharmacol Physiol 2007;34:792-795.
40. Pinho CM, Teixeira PF, Glaser E. Mitochondrial import and degradation of amyloid-beta peptide. Biochim Biophys Acta 2014;1837:1069-1074.
41. Calkins MJ, Reddy PH. Amyloid beta impairs mitochondrial anterograde transport and degenerates synapses in Alzheimer's disease neurons. Biochim Biophys Acta 2011;1812:507-513.
42. Rosales-Corral S, Acuna-Castroviejo D, Tan DX, et al. Accumulation of exogenous amyloid-beta peptide in hippocampal mitochondria causes their dysfunction: A protective role for melatonin. Oxid Med Cell Longev 2012;2012:843649.
43. Xie H, Guan J, Borrelli LA, Xu J, Serrano-Pozo A, Bacskai BJ. Mitochondrial alterations near amyloid plaques in an Alzheimer's disease mouse model. J Neurosci 2013;33:17042-17051.
44. Lustbader JW, Cirilli M, Lin C, et al. ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease. Science 2004;304:448-452.
45. Reddy PH, Beal MF. Amyloid beta, mitochondrial dysfunction and synaptic damage: Implications for cognitive decline in aging and Alzheimer's disease. Trends Mol Med 2008;14:45-53.
46. Rettberg JR, Yao J, Brinton RD. Estrogen: A master regulator of bioenergetic systems in the brain and body. Front Neuroendocrinol 2014;35:8-30.
47. Swerdlow RH, Burns JM, Khan SM. The Alzheimer's disease mitochondrial cascade hypothesis. J Alzheimers Dis 2010;20(Suppl 2):S265-S279.
48. Takuma K, Yao J, Huang J, et al. ABAD enhances Abeta-induced cell stress via mitochondrial dysfunction. FASEB J 2005;19:597-598.
49. Yao J, Rettberg JR, Klosinski LP, Cadenas E, Brinton RD. Shift in brain metabolism in late onset Alzheimer's disease: Implications for biomarkers and therapeutic interventions. Mol Aspects Med 2011;32:247-257.
50. Kang HK, Choi YH, Kwon H, et al. Estrogenic/antiestrogenic activities of a Epimedium koreanum extract and its major components: In vitro and in vivo studies. Food Chem Toxicol 2012;50:2751-2759.
51. Nilsen J, Irwin RW, Gallaher TK, Brinton RD. Estradiol in vivo regulation of brain mitochondrial proteome. J Neurosci 2007;27:14069-14077.
52. Yao J, Irwin R, Chen S, Hamilton R, Cadenas E, Brinton RD. Ovarian hormone loss induces bioenergetic deficits and mitochondrial beta-amyloid. Neurobiol Aging 2012;33:1507-1521.
53. Jayaraman A, Carroll JC, Morgan TE, et al. 17beta-estradiol and progesterone regulate expression of beta-amyloid clearance factors in primary neuron cultures and female rat brain. Endocrinology 2012;153:5467-5479.
54. Zhao L, Yao J, Mao Z, Chen S, Wang Y, Brinton RD. 17beta-Estradiol regulates insulin-degrading enzyme expression via an ERbeta/PI3-K pathway in hippocampus: Relevance to Alzheimer's prevention. Neurobiol Aging 2011;32:1949-1963.
55. Li F, Gong QH, Wu Q, Lu YF, Shi JS. Icariin isolated from Epimedium brevicornum Maxim attenuates learning and memory deficits induced by d-galactose in rats. Pharmacol Biochem Behav 2010;96:301-305.