UM
Human amyloid beta peptide and tau co-expression impairs behavior and causes specific gene expression changes in Caenorhabditis elegans
Wang, Chenyin; Saar, Valeria; Leung, Ka Lai; Chen, Liang; Wong, Garry
2018-01
Source PublicationNEUROBIOLOGY OF DISEASE
ISSN0969-9961
Volume109Pages:88-101
AbstractAlzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the presence of extracellular amyloid plaques consisting of Amyloid-beta peptide (A beta) aggregates and neurofibrillary tangles formed by aggregation of hyperphosphorylated microtubule-associated protein tau. We generated a novel invertebrate model of AD by crossing A beta 1-42 (strain CL2355) with either pro-aggregating tau (strain BR5270) or anti-aggregating tau (strain BR5271) pan-neuronal expressing transgenic Caenorhabditis elegans. The lifespan and progeny viability of the double transgenic strains were significantly decreased compared with wild type N2 (P< 0.0001). In addition, co-expression of these transgenes interfered with neurotransmitter signaling pathways, caused deficits in chemotaxis associative learning, increased protem aggregation visualized by Congo red staining, and increased neuronal loss. Global transcriptomic RNA-seq analysis revealed 248 up-and 805 down-regulated genes in N2 wild type versus Afi beta 1-42 + pro-aggregating tau animals, compared to 293 up-and 295 down-regulated genes in N2 wild type versus AJ31-42 + anti-aggregating tau animals. Gene set enrichment analysis of A beta 1-42 + pro-aggregating tau animals uncovered up-regulated annotation clusters UDP-glucur-onosyltransferase (5 genes, P< 4.2E-4), protein phosphorylation (5 genes, P< 2.60E-02), and aging (5 genes, P< 8.1E-2) while the down-regulated clusters included nematode cuticle collagen (36 genes, P< 1.5E-21).
KeywordCaenorhabditis elegans Alzheimer's disease Transcriptome analysis Amyloid beta Tau RNA interference
DOI10.1016/j.nbd.2017.10.003
URLView the original
Indexed BySCI
Language英语
WOS Research AreaNeurosciences & Neurology
WOS SubjectNeurosciences
WOS IDWOS:000418877600009
PublisherACADEMIC PRESS INC ELSEVIER SCIENCE
The Source to ArticleWOS
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Cited Times [WOS]:9   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Recommended Citation
GB/T 7714
Wang, Chenyin,Saar, Valeria,Leung, Ka Lai,et al. Human amyloid beta peptide and tau co-expression impairs behavior and causes specific gene expression changes in Caenorhabditis elegans[J]. NEUROBIOLOGY OF DISEASE,2018,109:88-101.
APA Wang, Chenyin,Saar, Valeria,Leung, Ka Lai,Chen, Liang,&Wong, Garry.(2018).Human amyloid beta peptide and tau co-expression impairs behavior and causes specific gene expression changes in Caenorhabditis elegans.NEUROBIOLOGY OF DISEASE,109,88-101.
MLA Wang, Chenyin,et al."Human amyloid beta peptide and tau co-expression impairs behavior and causes specific gene expression changes in Caenorhabditis elegans".NEUROBIOLOGY OF DISEASE 109(2018):88-101.
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