Abstract
Mutations in the human microtubule-associated protein tau (hMAPT) gene including R406W and V337M result in autosomal dominant neurodegenerative disorder. These mutations lead to hyperphosphorylation and aggregation of Tau protein which is a known genetic factor underlying development of Alzheimer’s disease (AD). In the present study, transgenic Drosophila models of AD expressing wild-type and mutant forms of hMAPT exhibit a progressive neurodegeneration which was manifested in the form of early death and impairment of cognitive ability. Moreover, they were also found to have significantly decreased activity of neurotransmitter enzymes accompanied by decreased cellular endogenous antioxidant profile. The extent of neurodegeneration, memory impairment, and biochemical profiles was different in the tau transgenic strains which indicate multiple molecular and cellular responses underlie each particular form of hMAPT.
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Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126
Ali YO, Ruan K, Zhai RG (2012) NMNAT suppresses tau-induced neurodegeneration by promoting clearance of hyperphosphorylated tau oligomers in a Drosophila model of tauopathy. Hum Mol Genet 21:237–250
Black MJ, Brand RB (1974) Spectrofluorometric analysis of hydrogen peroxide. Anal Biochem 58:246–254
Buege J, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310
Dias-Santagata D, Fulga TA, Duttaroy A, Feany MB (2007) Oxidative stress mediates tau-induced neurodegeneration in Drosophila. J Clin Investig 117:236–245
Ellman GL, Courtney KD, Andres V, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95
Fergestad T, Ganetzky B, Palladino MJ (2006) Neuropathology in Drosophila membrane excitability mutants. Genetics 172:1031–1042
Hutton M (2000) Molecular genetics of chromosome 17 tauopathies. Ann NY Acad Sci 920:63–73
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
Marcus DL, Thomas C, Rodriguez C, Simberkoff K, Tsai JS et al (1998) Increased peroxidation and reduced antioxidant enzyme activity in Alzheimer’s disease. Exp Neurol 150:40–44
Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474
Mershin A, Pavlopoulos E, Fitch O, Braden BC, Nanopoulos DV, Skoulakis EM (2004) Learning and memory deficits upon TAU accumulation in Drosophila mushroom body neurons. Learn Mem 11:277–287
Quinn WG, Dudai Y (1976) Memory phases in Drosophila. Nature 262:576–577
Rinne JO, Kaasinen V, Järvenpää T, Någren K, Roivainen A, Yu M et al (2003) Brain acetylcholinesterase activity in mild cognitive impairment and early Alzheimer’s disease. J Neurol Neurosurg Psychiatry 74:113–115
Rojo AI, Sagarra MR, Cuadrado A (2008) GSK-3b down-regulates the transcription factor Nrf2 after oxidant damage: relevance to exposure of neuronal cells to oxidative stress. J Neurochem 105:192–205
Schmatz R, Mazzanti CM, Spanevello R, Stefanello N, Gutierres J, Corrêa M et al (2009) Resveratrol prevents memory deficits and the increase in acetylcholinesterase activity in streptozotocin-induced diabetic rats. Eu J Pharmacol 610:42–48
Schneider CA, Rasband WS, Eliceiri KW (2012) NIH Image to ImageJ: 25 years of image analysis. Nat Methods 9:671–675
Spillantini MG, Murrell JR, Goedert M, Farlow MR, Klug A, Ghetti B (1998) Mutation in the tau gene in familial multiple system tauopathy with presenile dementia. Proc Natl Acad Sci USA 95:7737–7741
Wittmann CW et al (2001) Tauopathy in Drosophila: neurodegeneration without neurofibrillary tangles. Science 293:711–714
Yu D, Ponomarev A, Davis RL (2004) Altered representation of the spatial code for odors after olfactory classical conditioning; memory trace formation by synaptic recruitment. Neuron 42:437–449
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We thank the Chairman, Department of Studies in Zoology, University of Mysore, Mysore, for the facilities.
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Haddadi, M., Nongthomba, U. & Ramesh, S.R. Biochemical and Behavioral Evaluation of Human MAPT Mutations in Transgenic Drosophila melanogaster . Biochem Genet 54, 61–72 (2016). https://doi.org/10.1007/s10528-015-9701-1
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DOI: https://doi.org/10.1007/s10528-015-9701-1