NM  Vol.3 No.4 , December 2012
Clearance of Amyloid Beta Plaques from Brain of Alzheimeric Rats by Lavandula angustifolia
Abstract: An important marker in neurodegenerative Alzheimer’s disease (AD) is abnormal production of amyloid beta (Aβ) peptide leading to formation of plaques in the brain. Through decreasing Aβ aggregates, anti-inflammatory agents, phagocytosis, and proteolytic enzymes are known to decline risk of Aβ plaque formation. In the previous study we showed that aqueous extract of Lavandula angustifolia (lavender), with known anti-inflammatory effects, improves memory deficits in animal model of Alzheimer. Here, we assess if lavender play a role in clearance of Aβ plaques in the hippocampus. The Alzheimeric animals were created with intracerebroventricular injection of Aβ 1-42. To confirm formation of Aβ plaques, brain sections were stained by Congo red method. Twenty days post-injection they were administered with different doses (50, 100 and 200 mg/kg) of the aqueous extract of lavender for duration of 20 days. Our results demonstrated that 50 mg/kg of lavender not effectively influenced the Aβ plaques. On the other hand, the herbal medicine at the doses of 100 and 200 mg/kg markedly decreased the extent of Aβ aggregates. We concluded that the lavender extract dose dependently underlies elimination of Aβ plaques. The exact mechanism by which the herbal medicine removes the Aβ aggregates needs to be elucidated.
Cite this paper: M. Soheili, M. Tavirani and M. Salami, "Clearance of Amyloid Beta Plaques from Brain of Alzheimeric Rats by Lavandula angustifolia," Neuroscience and Medicine, Vol. 3 No. 4, 2012, pp. 362-367. doi: 10.4236/nm.2012.34044.

[1]   H. W. Querfurth and F. M. LaFerla, “Alzheimer’s Disease,” The New England Journal of Medicine, Vol. 362, No. 4, 2010, pp. 329-344. doi:10.1056/NEJMra0909142

[2]   J. Wang, et al., “Increased Oxidative Damage in Nuclear and Mitochondrial DNA in Alzheimer’s Disease,” Journal of Neurochemistry, Vol. 93, No. 4, 2005, pp. 953-962. doi:10.1111/j.1471-4159.2005.03053.x

[3]   H. Hampel, et al., “Biological Markers of Amyloid β-Related Mechanisms in Alzheimer’s Disease,” Experimental Neurology, Vol. 223, No. 2, 2010, pp. 334-346. doi:10.1016/j.expneurol.2009.09.024

[4]   I. Espuny-Camacho, et al., “Peroxisome Proliferator-Activated Receptor Gamma Enhances the Activity of an Insulin Degrading Enzyme-Like Metalloprotease for Amyloid-Beta Clearance,” Journal of Alzheimer’s Disease, Vol. 20, No. 4, 2010, pp. 1119-1132.

[5]   G. Yamin, “NMDA Receptor-Dependent Signaling Pathways that Underlie Amyloid Beta-Protein Disruption of LTP in the Hippocampus,” Journal of Neuroscience Research, Vol. 87, No. 8, 2009, pp. 1729-1736. doi:10.1002/jnr.21998

[6]   E. Mugantseva and I. Podolski, “Animal Model of Alzheimer’s Disease: Characteristics of EEG and Memory,” Vol. 4, No. 4, 2009, pp. 507-514.

[7]   K. Yamada and T. Nabeshima, “Animal Models of Alzheimer’s Disease and Evaluation of Anti-Dementia Drugs,” Pharmacology & Therapeutics, Vol. 88, No. 2, 2000, pp. 93-113. doi:10.1016/S0163-7258(00)00081-4

[8]   B. Jeynes and J. Provias, “Evidence for Altered LRP/ RAGE Expression in Alzheimer Lesion Pathogenesis,” Current Alzheimer Research, Vol. 5, No. 5, 2008, pp. 432-437. doi:10.2174/156720508785908937

[9]   K. K. Kandimalla, et al., “Pharmacokinetic Analysis of the Blood-Brain Barrier Transport of 125I-Amyloid Beta Protein 40 in Wild-Type and Alzheimer’s Disease Transgenic Mice (APP,PS1) and Its Implications for Amyloid Plaque Formation,” Journal of Pharmacology and Experimental Therapeutics, Vol. 313, No. 3, 2005, pp. 1370-1378. doi:10.1124/jpet.104.081901

[10]   Y. Nishida, et al., “Depletion of Vitamin E Increases Amyloid Beta Accumulation by Decreasing Its Clearances from Brain and Blood in a Mouse Model of Alzheimer Disease,” The Journal of Biological Chemistry, Vol. 284, No. 48, 2009, pp. 33400-33408. doi:10.1074/jbc.M109.054056

[11]   B. Cameron and G. E. Landreth, “Inflammation, Microglia, and Alzheimer’s Disease,” Neurobiology of Disease, Vol. 37, No. 3, 2010, pp. 503-509. doi:10.1016/j.nbd.2009.10.006

[12]   A. R. Simard, et al., “Bone Marrow-Derived Microglia Play a Critical Role in Restricting Senile Plaque Formation in Alzheimer’s Disease,” Neuron, Vol. 49, No. 4, 2006, pp. 489-502. doi:10.1016/j.neuron.2006.01.022

[13]   S. E. Hickman, E. K. Allison and J. El Khoury, “Microglial Dysfunction and Defective Beta-Amyloid Clearance Pathways in Aging Alzheimer’s Disease Mice,” The Journal of Neuroscience, Vol. 28, No. 33, 2008, pp. 8354-8360. doi:10.1523/JNEUROSCI.0616-08.2008

[14]   M. A. Leissring, et al., “Enhanced Proteolysis of Beta-Amyloid in APP Transgenic Mice Prevents Plaque Formation, Secondary Pathology, and Premature Death,” Neuron, Vol. 40, No. 6, 2003, pp. 1087-1093. doi:10.1016/S0896-6273(03)00787-6

[15]   P. P. Yan, et al., “Matrix Metalloproteinase-9 Degrades Amyloid-Beta Fibrils in Vitro and Compact Plaques in Situ,” The Journal of Biological Chemistry, Vol. 281, No. 34, 2006, pp. 24566-24574. doi:10.1074/jbc.M602440200

[16]   N. Iwata, et al., “Region-Specific Reduction of a Beta-Degrading Endopeptidase, Neprilysin, in Mouse Hippocampus upon Aging,” The Journal of Neuroscience Research, Vol. 70, No. 3, 2002, pp. 493-500. doi:10.1002/jnr.10390

[17]   N. Iwata, et al., “Metabolic Regulation of Brain Abeta by Neprilysin,” Science, Vol. 292, No. 5521, 2001, pp. 1550-1552. doi:10.1126/science.1059946

[18]   K. Yasojima, et al., “Reduced Neprilysin in High Plaque Areas of Alzheimer Brain: A Possible Relationship to Deficient Degradation of Beta-Amyloid Peptide,” Neuroscience Letters, Vol. 297, No. 2, 2001, pp. 97-100. doi:10.1016/S0304-3940(00)01675-X

[19]   K. Yasojima, E. G. McGeer and P. P. L. McGeer, “Relationship between Beta Amyloid Peptide Generating Molecules and Neprilysin in Alzheimer Disease and Normal Brain,” Brain Research, Vol. 919, No. 1, 2001, pp. 115-121. doi:10.1016/S0006-8993(01)03008-6

[20]   B. J. Bacskai, et al., “Non-Fc-Mediated Mechanisms are Involved in Clearance of Amyloid-Beta in Vivo by Immunotherapy,” The Journal of Neuroscience, Vol. 22, No. 18, 2002, pp. 7873-7878.

[21]   Y. Levites, et al., “Intracranial Adeno-Associated Virus-Mediated Delivery of Anti-Pan Amyloid Beta, Amyloid Beta40, and Amyloid Beta42 Single-Chain Variable Fragments Attenuates Plaque Pathology in Amyloid Precursor Protein Mice,” The Journal of Neuroscience, Vol. 26, No. 46, 2006, pp. 11923-11928. doi:10.1523/JNEUROSCI.2795-06.2006

[22]   D. Schenk, et al., “Immunization with Amyloid-Beta Attenuates Alzheimer-Disease-Like Pathology in the PDAPP Mouse,” Nature, Vol. 400, No. 6740, 1999, pp. 173-177. doi:10.1038/22124

[23]   M. Shibata, et al., “Clearance of Alzheimer’s Amyloid-Ss(1-40) Peptide from Brain by LDL Receptor-Related Protein-1 at the Blood-Brain Barrier,” Journal of Clinical Investigation, Vol. 106, No. 12, 2000, pp. 1489-1499. doi:10.1172/JCI10498

[24]   D. J. Selkoe, “Clearing the Brain’s Amyloid Cobwebs,” Neuron, Vol. 32, No. 2, 2001, pp. 177-180. doi:10.1016/S0896-6273(01)00475-5

[25]   B. A. in’t Veld, et al., “Nonsteroidal Antiinflammatory Drugs and the Risk of Alzheimer’s Disease,” The New England Journal of Medicine, Vol. 345, No. 21, 2001, pp. 1515-1521.

[26]   M. E. Buyukokuroglu, et al., “The Effects of Aqueous Extract of Lavandula Angustifolia Flowers in Glutamate-Induced Neurotoxicity of Cerebellar Granular Cell Culture of Rat Pups,” Journal of Ethnopharmacology, Vol. 84, No. 1, 2003, pp. 91-94. doi:10.1016/S0378-8741(02)00286-6

[27]   M. S. Kashani, et al., “Aqueous Extract of Lavender (Lavandula Angustifolia) Improves the Spatial Performance of a Rat Model of Alzheimer’s Disease,” Neuroscience Bulletin, Vol. 27, No. 2, 2011, pp. 99-106. doi:10.1007/s12264-011-1149-7

[28]   H. M. Kim and S. H. Cho, “Lavender Oil Inhibits Immediate-Type Allergic Reaction in Mice and Rats,” Journal of Pharmacy and Pharmacology, Vol. 51, No. 2, 1999, pp. 221-226. doi:10.1211/0022357991772178

[29]   P. P. W. Lin, et al., “Efficacy of Aromatherapy (Lavandula Angustifolia) as an Intervention for Agitated Behaviours in Chinese Older Persons with Dementia: A Cross-Over Randomized Trial,” International Journal of Geriatric Psychiatry, Vol. 22, No. 5, 2007, pp. 405-410. doi:10.1002/gps.1688

[30]   M. Lis-Balchin and S. Hart, “Studies on the Mode of Action of the Essential Oil of Lavender (Lavandula Angustifolia PP. Miller),” Phytotherapy Research, Vol. 13, No. 6, 1999, pp. 540-542. doi:10.1002/(SICI)1099-1573(199909)13:6<540::AID-PTR523>3.0.CO;2-I

[31]   M. Bourin, N. Ripoll and E. Dailly, “Nicotinic receptors and Alzheimer’s disease,” Current Medical Research and Opinion, Vol. 19, No. 3, 2003, pp. 169-177. doi:10.1185/030079903125001631

[32]   A. Adsersen, et al., “Screening of Plants Used in Danish Folk Medicine to Treat Memory Dysfunction for Acetylcholinesterase Inhibitory Activity,” Journal of Ethnopharmacology, Vol. 104, No. 3, 2006, pp. 418-422. doi:10.1016/j.jep.2005.09.032

[33]   T. Umezu, et al., “Anticonflict Effects of Lavender Oil and Identification of Its Active Constituents,” Pharmacology Biochemistry and Behavior, Vol. 85, No. 4, 2006, pp. 713-721. doi:10.1016/j.pbb.2006.10.026

[34]   Y. Kim, et al., “Effect of Lavender Oil on Motor Function and Dopamine Receptor Expression in the Olfactory Bulb of Mice,” Journal of Ethnopharmacology, Vol. 125, No. 1, 2009, pp. 31-35. doi:10.1016/j.jep.2009.06.017

[35]   A. Budantsev, et al., “[The Brain in Stereotaxic Coordinates (a Textbook for Colleges)],” Zhurnal Vysshe? Nervno? Deiatelnosti Imeni I P Pavlova, Vol. 43, No. 5, 1993, pp. 1045-1051.

[36]   D. M. Wilcock, M. N. Gordon and D. Morgan, “Quantification of Cerebral Amyloid Angiopathy and Parenchymal Amyloid Plaques with Congo Red Histochemical Stain,” Nature Protocols, Vol. 1, No. 3, 2006, pp. 1591-1595. doi:10.1038/nprot.2006.277

[37]   R. Deane, et al., “A Multimodal RAGE-Specific Inhibitor Reduces Amyloid Beta-Mediated Brain Disorder in a Mouse Model of Alzheimer Disease,” Journal of Clinical Investigation, Vol. 122, No. 4, 2012, pp. 1377-1392. doi:10.1172/JCI58642

[38]   A. Mathew, et al., “Alzheimer’s Disease: Cholesterol a Menace?” Brain Research Bulletin, Vol. 86, No. 1-2, 2011, pp. 1-12. doi:10.1016/j.brainresbull.2011.06.006

[39]   E. T. Parkin, et al., “Cellular Prion Protein Regulates Beta-Secretase Cleavage of the Alzheimer’s Amyloid Precursor Protein,” PNAS, Vol. 104, No. 26, 2007, pp. 11062-11067. doi:10.1073/pnas.0609621104

[40]   S. K. Gill, et al., “82-KDa Choline Acetyltransferase Is in Nuclei of Cholinergic Neurons in Human CNS and Altered in Aging and Alzheimer Disease,” Neurobiology of Aging, Vol. 28, No. 7, 2007, pp. 1028-1040. doi:10.1016/j.neurobiolaging.2006.05.011

[41]   E. E. Tuppo and H. R. Arias, “The Role of Inflammation in Alzheimer’s Disease,” The International Journal of Biochemistry & Cell Biology, Vol. 37, No. 2, 2005, pp. 289-305. doi:10.1016/j.biocel.2004.07.009

[42]   Q. Yan, et al., “Anti-Inflammatory Drug Therapy Alters Beta-Amyloid Processing and Deposition in an Animal Model of Alzheimer’s Disease,” The Journal of Neuroscience, Vol. 23, No. 20, 2003, pp. 7504-7509.

[43]   V. Hajhashemi, A. Ghannadi and B. Sharif, “Anti-Inflammatory and Analgesic Properties of the Leaf Extracts and Essential Oil of Lavandula Angustifolia Mill,” Journal of Ethnopharmacology, Vol. 89, No. 1, 2003, pp. 67-71. doi:10.1016/S0378-8741(03)00234-4

[44]   S. Fukami, et al., “Abeta-Degrading Endopeptidase, Neprilysin, in Mouse Brain: Synaptic and Axonal Localization Inversely Correlating with Abeta Pathology,” Neuroscience Research, Vol. 43, No. 1, 2002, pp. 39-56. doi:10.1016/S0168-0102(02)00015-9

[45]   R. A. Marr, et al., “Neprilysin Gene Transfer Reduces Human Amyloid Pathology in Transgenic Mice,” The Journal of Neuroscience, Vol. 23, No. 6, 2003, pp. 1992-1996.

[46]   N. Iwata, et al., “Presynaptic Localization of Neprilysin Contributes to Efficient Clearance of Amyloid-Beta Peptide in Mouse Brain,” The Journal of Neuroscience, Vol. 24, No. 4, 2004, pp. 991-998. doi:10.1523/JNEUROSCI.4792-03.2004