Dual PINK Mutant and Aβ42-Dependent Lifespan Shorten and Flight Impairment in Transgenic Drosophila Partially Alleviates by a Lactococcus lactis Supplemented Diet


Oxidative stress has been strongly related with Parkinson disease (PD) and Alzheimer disease pathogenesis. We determined the effects of Lactococcus lactis (LAL) supplementation on the generated loss-of-function mutants of PINK1 B9, an AR-JP-linked gene and Aβ42 induced phenotypes in a Drosophila melanogaster model of PD/AD. Enhanced mutant PINK1 B9 and Aβ42 expression in D. melanogaster dopaminergic (DA) neurons can curtail lifespan, flight muscle accompanied by locomotive defects and we have observed longevity methods to assay the effects of LAL on D. melanogaster survival. Furthermore, flies expressing mutant PINK1 B9 and Aβ42 in their brain fed LAL had up to the two weeks, or 25%, greater median lifespan than those fed a standard sucrose diet. In addition, LAL improved mutant PINK1 B9 and Aβ42-induced flight impairments in the Drosophila wing. Our microscopy analyses revealed that individuals fed LAL had improved atypical ommatidia as well as an increased thirteen percentage of flight ability than those fed a control diet. We propose that LAL, rich in naturally occurring probiotics and antioxidants, promotes the survival of neurons in brain and wing muscle tissues with increased levels of mutant PINK1 B9 and Aβ42 via a protective cell survival mechanism.

Share and Cite:

Ko, D. , Eun, Y. , Na, J. and Kim, S. (2015) Dual PINK Mutant and Aβ42-Dependent Lifespan Shorten and Flight Impairment in Transgenic Drosophila Partially Alleviates by a Lactococcus lactis Supplemented Diet. Journal of Behavioral and Brain Science, 5, 266-273. doi: 10.4236/jbbs.2015.57027.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Yoon, J.H., Lee, J.E., Yong, S.W., Moon, S.Y. and Lee, P.H. (2014) The Mild Cognitive Impairment Stage of Dementia with Lewy Bodies and Parkinson Disease: A Comparison of Cognitive Profiles. Alzheimer Disease and Associated Disorders, 28, 151-155.
[2] Gautier, C.A., Corti, O. and Brice, A. (2014) Mitochondrial Dysfunctions in Parkinson’s Disease. Revista de Neurología, 170, 339-343.
[3] Valente, E.M., et al. (2004) Hereditary Early-Onset Parkinson’s Disease Caused by Mutations in PINK1. Science, 304, 1158-1160.
[4] Park, J., Lee, S.B., Lee, S., Kim, Y., Song, S., Kim, S., Bae, E., Kim, J., Shong, M., Kim, J.M. and Chung, J. (2006) Mitochondrial Dysfunction in Drosophila PINK1 Mutants Is Complemented by Parkin. Nature, 441, 1157-1161.
[5] Schapira, A.H. and Jenner, P. (2011) Etiology and Pathogenesis of Parkinson’s Disease. Movement Disorders, 26, 1049-1055.
[6] Byers, B., Cord, B., Nguyen, H.N., Schüle, B., Fenno, L., Lee, P.C., Deisseroth, K., Langston, J.W., Pera, R.R. and Palmer, T.D. (2011) SNCA Triplication Parkinson’s Patient’s iPSC-Derived DA Neurons Accumulate α-Synuclein and Are Susceptible to Oxidative Stress. PLoS ONE, 6, e26159.
[7] Huang, X., Atwood, C.S., Hartshorn, M.A., Multhaup, G., Goldstein, L.E., Scarpa, R.C., Cuajungco, M.P., Gray, D.N., Lim, J., Moir, R.D., Tanzi, R.E. and Bush, A.I. (1999) The A Beta Peptide of Alzheimer’s Disease Directly Produces Hydrogen Peroxide through Metal Ion Reduction. Bio-chemistry, 38, 7609-7616.
[8] Bush, A.I. (2003) Themetallobiology of Alzheimer’s Disease. Trends in Neurosciences, 26, 207-214.
[9] Abramov, A.Y., Canevari, L. and Duchen, M.R. (2004) Beta-Amyloid Peptides Induce Mitochondrial Dysfunction and Oxidative Stress in Astrocytes and Death of Neurons through Activation of NADPH Oxidase. Journal of Neuroscience, 24, 565-575.
[10] Kienlen-Campard, P., Miolet, S., Tasiaux, B. and Octave, J.N. (2002) Intracellular Amyloid-Beta 1-42, but Not Extracellular Soluble Amyloid-Beta Peptides, Induces Neuronal Apoptosis. Journal of Biological Chemistry, 277, 5666-5670.
[11] Wei, W., Norton, D.D., Wang, X. and Kusiak, J.W. (2002) Abeta 17-42 in Alzheimer’s Disease Activates JNK and Caspase-8 Leading to Neuronal Apoptosis. Brain, 125, 2036-2043.
[12] Cao, W., Song, H.J., Gangi, T., Kelkar, A., Antani, I., Garza, D. and Konsolaki, M. (2008) Identification of Novel Genes That Modify Phenotypes Induced by Alzheimer’s β-Amyloid Overexpression in Drosophila. Genetics, 178, 1457-1471.
[13] Linder, J.E. and Promislow, D.E. (2009) Cross-Generational Fitness Effects of Infection in Drosophila melanogaster. Fly, 3, 143-150.
[14] Crowther, D.C., Kinghorn, K.J., Miranda, E., Page, R., Curry, J.A., Duthie, F.A., Gubb, D.C. and Lomas, D.A. (2005) Intraneuronal Aβ, Non-Amyloid Aggregates and Neurodegeneration in a Drosophila Model of Alzheimer’s Disease. Neuroscience, 132, 123-135.
[15] Nilsberth, C., Westlind-Danielsson, A., Eckman, C.B., Condron, M.M., Axelman, K., Forsell, C., Stenh, C., Luthman, J., Teplow, D.B., Younkin, S.G., Naslund, J. and Lannfelt, L. (2001) The “Arctic” APP Mutation (E693G) Causes Alzheimer’s Disease by Enhanced Aβ Protofibril Formation. Nature Neuroscience, 4, 887-893.
[16] Hong, Y.K., Lee, S., Park, S.H., Lee, J.H., Han, S.Y., Kim, S.T., Kim, Y.K., Jeon, S., Koo, B.S. and Cho, K.S. (2012) Inhibition of JNK/dFOXO Pathway and Caspases Rescues Neurological Impairments in Drosophila Alzheimer’s Disease Model. Biochemical and Biophysical Research Communications, 419, 49-53.
[17] Abramoff, M.D., Magalhaes, P.J. and Ram, S.J. (2004) Image Processing with Image. Biophotonics International, 11, 36-42.
[18] Pesah, Y., Pham, T., Burgess, H., Middlebrooks, B., Verstreken, P., Zhou, Y., et al. ((2004) Drosophila Parkin Mutants Have Decreased Mass and Cell Size and Increased Sensitivity to Oxygen Radical Stress. Development, 131, 2183-2194.
[19] Leulier, F., Ribeiro, P.S., Palmer, E., Tenev, T., Takahashi, K., Robertson, D., et al. (2006) Systematic in Vivo RNAi Analysis of Putative Components of the Drosophila Cell Death Machinery. Cell Death and Differentiation, 13, 1663-1674.
[20] Vander Heiden, M.G., Chandel, N.S., Williamson, E.K., Schumacker, P.T. and Thompson, C.B. (1997) Bcl-xL Regulates the Membrane Potential and Volume Homeostasis of Mitochondria. Cell, 91, 627-637.
[21] Vander Heiden, M.G. and Thompson, C.B. (1999) Bcl-2 Proteins: Regulators of Apoptosis or of Mitochondrial Homeostasis? Nature Cell Biology, 1, E209-E216.
[22] Seo, J.S., Jung, E.Y., Kim, J.H., Lyu, Y.S., Han, P.L. and Kang, H.W. (2010) A Modified Preparation (LMK03) of the Oriental Medicine Jangwonhwan Reduces Aβ1-42 Level in the Brain of Tg-APPswe/PS1dE9 Mouse Model of Alzheimer Disease. Journal of Ethnopharmacology, 130, 578-585.
[23] Seo, J.S., Yun, J.H., Baek, I.S., Leem, Y.H., Kang, H.W., Cho, H.K., Lyu, Y.S., Son, H.J. and Han, P.L. (2010) Oriental Medicine Jangwonhwan Reduces Aβ1-42 Level and Beta-Amyloid Deposition in the Brain of Tg-APPswe/PS1dE9 Mouse Model of Alzheimer Disease. Journal of Ethnopharmacology, 128, 206-212.
[24] Kaushal, D. and Kansal, V.K. (2012) Probiotic Dahi Containing Lactobacillus acidophilus and Bifidobacterium bifidum Alleviates Age-Inflicted Oxidative Stress and Improves Expression of Biomarkers of Ageing in Mice. Molecular Biology Reports, 39, 1791-1799.
[25] Grompone, G., Martorell, P., Llopis, S., González, N., Genovés, S., Mulet, A.P., Fernández-Calero, T., Tiscornia, I., Bollati-Fogolín, M., Chambaud, I., Foligné, B., Montserrat, A. and Ramón, D. (2012) Anti-Inflammatory Lactobacillus rhamnosus CNCM I-3690 Strain Protects against Oxidative Stress and Increases Lifespan in Caenorhabditis elegans. PLoS ONE, 12, e52493.
[26] Lee, K.A. and Lee, W.J. (2014) Drosophila as a Model for Intestinal Dysbiosis and Chronic Inflammatory Diseases. Developmental & Comparative Immunology, 42, 102-110.
[27] Schriner, S.E., Katoozi, N.S., Pham, K.Q., Gazarian, M., Zarban, A. and Jafari, M. (2012) Extension of Drosophila lifespan by Rosa damascena Associated with an Increased Sensitivity to Heat. Biogerontology, 13, 105-117.
[28] Peng, C., Chan, H.Y., Huang, Y., Yu, H. and Chen, Z.Y. (2011) Apple Polyphenols Extend the Mean Lifespan of Drosophila melanogaster. Journal of Agricultural and Food Chemistry, 59, 2097-2106.
[29] Long, J., Gao, H., Sun, L., Liu, J. and Zhao-Wilson, X. (2009) Grape Extract Protects Mitochondria from Oxidative Damage and Improves Locomotor Dysfunction and Extends Lifespan in a Drosophila Parkinson’s Disease Model. Rejuvenation Research, 12, 321-331.
[30] Li, Y.M., Chan, H.Y., Huang, Y. and Chen, Z.Y. (2007) Green Tea Catechins Upregulate Superoxide Dismutase and Catalase in Fruit Flies. Molecular Nutrition & Food Research, 51, 546-554.
[31] Peng, C., Chan, H.Y., Li, Y.M., Huang, Y. and Chen, Z.Y. (2009) Black Tea Theaflavins Extend the Lifespan of Fruit Flies. Experimental Gerontology, 44, 773-783.

Copyright © 2022 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.