A semi-automated motion-tracking analysis of locomotion speed in the C. elegans transgenics overexpressing beta-amyloid in neurons

Machino, Kevin; Link, Christopher D.; Murakami, Hana; Murakami, Shin

doi:10.3389/fgene.2014.00202

Cited by 25 publications

(34 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is well documented that the transgenic expression of human Aβ in the body wall muscle cells of C. elegans results in progressive paralysis [57,498]. We found that either 1% glucose or 1% glycerol alleviated paralysis in Aβ transgenic worms.…”

Section: Discussionmentioning

confidence: 50%

“…Machino et al found lower fecundity and increased egg hatching time in neuronal Aβ expressing worms. [498]. We find that both glucose and glycerol induced further dose-dependent impairment of fecundity and egg viability in worms that express Aβ in neurons.…”

Section: Discussionmentioning

confidence: 71%

“…Despite impairing neuronal controlled behaviors, Aβ expression also reduce fecundity and increased egg hatching time in C. elegans [498]. Although MICA improved fecundity and reduced egg hatching time in Aβ expressing worms, it was not up to the matching controls.…”

Section: Discussionmentioning

confidence: 91%

“…Like muscular impairment, Aβ expression in C. elegans neuronal cells is associated with many behavioral defects like reduced chemotaxis, serotonin hypersensitivity, and impaired fecundity and egg hatching [57,498]. The defects in these behaviors can be associated with impaired ACh signaling [497].…”

Section: Discussionmentioning

confidence: 99%

“…Assays for cellular dysfunction due to neuronal expression of Aβ in C. elegans include impaired chemotaxis, serotonin hypersensitivity, and egg laying and hatching [57,498]. The presence of Aβ is also known to decrease fecundity and increase egg hatching time in C. elegans [498], so we tested whether MICA could reverse these effects. The fecundity of the Aβ strain CL2355 was indeed lower than its matched control (157±7.5 vs 270±7.9, p< 0.0001) ( Figure 5.4C).…”

Section: Mica Up To 10mm Does Not Alter Dld-1 Gene or Protein Expressionmentioning

confidence: 99%

See 4 more Smart Citations

Metabolic study of Alzheimer’s disease using mutant C. elegans

Ahmad¹

View full text Add to dashboard Cite

Alzheimer's disease (AD) is associated with chronic neurodegeneration and is the cause of the most common form of dementia. The main hallmarks of AD are aggregates of amyloid beta (Aβ) and formation of hyperphosphorylated tau neurofibrillary tangles (NFTs). Unfortunately, after more than 100 years of research the exact cause(s) and mechanisms involved in AD progression remain unclarified. Evidence indicates that impaired mitochondrial bioenergetics may precede by decades, the neurodegeneration and cognitive decline associated with AD. Moreover, a genetic association of the core metabolic enzyme dihydrolipoamide dehydrogenase (DLD) with late-onset AD and reduced activity of DLD-containing enzymes suggests glucose hypo-metabolism as a possible cause of AD. Contrary to this, improvements of AD symptoms under caloric restriction or other means of reducing-glucose dependent energy metabolism supports an alternative hypothesis that a decrease in glucose metabolism may be protective. In the present study, we used mutant Caenorhabditis elegans (C. elegans) to investigate the effect of glucose metabolism on AD progression. We initially looked at the role of suppressed DLD-1, and then we focused on the effect of high glucose in AD pathogenesis.Transgenic expression of Aβ in C. elegans causes both phenotypic and behavioral defects and results in accumulation of toxic Aβ oligomers, culminating in protein aggregation as is normally associated with AD pathophysiology. Aβ expression in worm muscle causes agedependent progressive paralysis and impaired acetylcholine neurotransmission while neuronal Aβ expression results in defective chemotaxis and impaired serotonin sensitivity as well as reduced fecundity and egg hatching. Suppression of the dld-1 gene alleviated paralysis, improved acetylcholine neurotransmission, enhanced chemotaxis and restored normal sensitivity to serotonin.dld-1 gene suppression also protects vitality as indicated by improved fecundity and egg hatching.Interestingly, protective effects of dld-1 suppression could be reversed using the calcium ionophore (CaI), indicating that the protective mechanism involves calcium signaling. Each of these beneficial effects of dld-1 gene suppression could be mimicked using a specific, small molecule inhibitor of the DLD-1 enzyme, 5-methoxyindole-2-carboxylic acid (MICA).High glucose levels are associated with the metabolic disorder, diabetes, which is a major risk factor for AD. In fact, it has been suggested that AD is a neural form of diabetes, type 3 diabetes. If true, drugs used to treat diabetes could act as possible treatments for AD. In this study, I investigated the effect of elevated glucose, the glucose metabolism inhibitor, 2-deoxy-d-glucose ii (2DOG) as well as the anti-diabetes drugs, metformin and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), on AD progression. Elevated glucose in the growth medium induced hyperactivity, which interfered with the paralysis assays, but it was seen to impair cholinergic neurotransmission, egg laying and hatc...

show abstract

Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Mica Up To 10mm Does Not Alter Dld-1 Gene or Protein Expressionmentioning

confidence: 99%

See 3 more Smart Citations

Metabolic study of Alzheimer’s disease using mutant C. elegans

Ahmad¹

View full text Add to dashboard Cite

show abstract

Metformin Attenuates Aβ Pathology Mediated Through Levamisole Sensitive Nicotinic Acetylcholine Receptors in a C. elegans Model of Alzheimer’s Disease

Ahmad

Ebert

2016

Mol Neurobiol

View full text Add to dashboard Cite

The metabolic disease, type 2 diabetes mellitus (T2DM), is a major risk factor for Alzheimer's disease (AD). This suggests that drugs such as metformin that are used to treat T2DM may also be therapeutic toward AD and indicates an interaction between AD and energy metabolism. In this study, we have investigated the effects of metformin and another T2DM drug, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) in C. elegans expressing human Aβ. We found that Aβ expressed in muscle inhibited levamisole sensitive nicotinic acetylcholine receptors and that metformin delayed Aβ-linked paralysis and improved acetylcholine neurotransmission in these animals. Metformin also moderated the effect of neuronal expression of Aβ: decreasing hypersensitivity to serotonin, restoring normal chemotaxis, and improving fecundity. Metformin was unable to overcome the small effect of neuronal Aβ on egg viability. The protective effects of metformin were associated with a decrease in the amount of toxic, oligomeric Aβ. AICAR has a similar protective effect against Aβ toxicity. This work supports the notion that anti-diabetes drugs and metabolic modulators may be effective against AD and that the worm model can be used to identify the specific interactions between Aβ and cellular proteins.

show abstract

Approaches to the Assessment of Frailty in Animal Models

Kane

Howlett

2018

Conn's Handbook of Models for Human Aging

View full text Add to dashboard Cite

A semi-automated motion-tracking analysis of locomotion speed in the C. elegans transgenics overexpressing beta-amyloid in neurons

Cited by 25 publications

References 30 publications

Metabolic study of Alzheimer’s disease using mutant C. elegans

Metabolic study of Alzheimer’s disease using mutant C. elegans

Metformin Attenuates Aβ Pathology Mediated Through Levamisole Sensitive Nicotinic Acetylcholine Receptors in a C. elegans Model of Alzheimer’s Disease

Approaches to the Assessment of Frailty in Animal Models

Contact Info

Product

Resources

About