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Ivermectin Effects on Ivermectin Effects on Caenorhabditis elegans Caenorhabditis elegans
(C.elegans)(C.elegans)
Moyosore Olagoke
Ivermectin C.elegans
Background InformationBackground Information
1.Anti-parasitic MedicationStrongyloides stercoralis
Onchocerciasis volvulus Pubic lice infestation Scabies Wuchereria bancrofti
2 Mechanism of action Bind to GABA Channel Hyperpolarization by ↑Cl Permeability
http://www.pnas.org/cgi/content/full/97/6/2674/F2
C95H146O28
Background InformationBackground Information
Phylum NematodaPhylum Nematoda
Feed on OP50 bacteriaFeed on OP50 bacteria
PseudocoelomatesPseudocoelomates
Thrashing motion (contraction)Thrashing motion (contraction)
Female deposit 100,000 or more egg/dayFemale deposit 100,000 or more egg/day
Most individuals are HermaphroditesMost individuals are Hermaphrodites
Life Cycle : >12hoursLife Cycle : >12hours
Caenorhabditis elegans
ResearchResearch
Purpose :To determine the effect of Purpose :To determine the effect of Ivermectin on Ivermectin on wild type ( wild type (C.elegansC.elegans))
Plan to extend strainPlan to extend strain
ComplicationsComplications Method of introductionMethod of introduction Drug TestDrug Test Resistance strainResistance strain
Ivermectin response to OP50 Ivermectin response to OP50
bacteriabacteria Ivermectin has no effect on OP-50 Ivermectin has no effect on OP-50
bacteria bacteria
Avermectin is isolated from strepto Avermectins
Drug IntroductionDrug Introduction
Ivermectin→ Agar
Sample calculation
Stock 1- 0.1g/1000цl in 100% DMSO
Stock 2- 10цl of stock 1 in 9.99ml 1%DMSO
15цl of stock 2 in 8цl Agar
10цg/цl x 15цl= 150цg
150 цg/8цl = 62.5цg/цl
Wild type Wild type C.elegansC.elegans
Ivermectin: Wildtype Ivermectin: Wildtype wormworm
62.5цg/цl
Fewer numbers
No apparent movement
Worm appears transparent
18.75цg/цlSame conclusionMovement is perceived (~3 worms)
ComparisonComparison
IvermectinControl
Touch insensitiveTouch insensitive=Tapping=Tapping
Future AnalysisFuture Analysis
Growth Assay: Growth Assay: Count the number of gravid Count the number of gravid adult adult
Reflects Pharyngeal functionReflects Pharyngeal function
Mechanosensation: Mechanosensation: Touch sensitivity Touch sensitivity
Neurological ResponseNeurological Response
Motility assay: Motility assay: Number of worm still Number of worm still thrashingthrashing
LocomotionLocomotion
ReferencesReferences
American Society of, Health-System Pharmacists Inc.American Society of, Health-System Pharmacists Inc. Patient Drug Information From MedMasterPatient Drug Information From MedMaster. .
Maryland: 2007.Maryland: 2007.
Jamison, Dean T., and Joel G. Breman. Jamison, Dean T., and Joel G. Breman. Disease Control Priorities in Developing CountriesDisease Control Priorities in Developing Countries. 2nd. New York: . 2nd. New York:
Oxford University Press, 1993.Oxford University Press, 1993.
John Keane and Leon Avery John Keane and Leon Avery Mechanosensory inputs influence Caenorhabditis elegansMechanosensory inputs influence Caenorhabditis elegans pharyngeal activity via ivermectin sensitivity genes.pharyngeal activity via ivermectin sensitivity genes. Genetics. 2003 May; 164(1): 153–162. PMCID: PMC1462566Genetics. 2003 May; 164(1): 153–162. PMCID: PMC1462566
Griffiths, Anthony J.F., and Jeffery H. Miller. Griffiths, Anthony J.F., and Jeffery H. Miller. HumanGeneticsHumanGenetics. . 7th ed. New York: W.H. Freeman,1996.7th ed. New York: W.H. Freeman,1996.
Hart, Anne C. "Behavior." Hart, Anne C. "Behavior." Worm BookWorm Book July 3 2006. 04 April 2008July 3 2006. 04 April 2008<http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=wormbook.<http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=wormbook.
capter.7133capter.7133>.>.
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