Lab Meeting 2: Literature search on how to quantify and measure

hypothesisPaige O’Donnell, investigator

December 12, 2008

Overview

Slide 1:Question Slide 2:Hypothesis Slide 3:How cardiovascular anomalies

are caused Slide 4:Development of zebrafish Slide 5:Testing my hypothesis Slide 6:Continuation of “Testing my

hypothesis”

Question

Are the defects that are caused by fluoxentive and paroxetine dependent on the dosage given?

Hypothesis

I hypothesize that the dosage amount will determine the extent of the defects that are caused by the SSRIs, fluoxetine and paroxetine.

Cardiovascular Anomalies

Usually occur within the first ten weeks of a human fetus› Very beginning of development

Present at birth A two day zebrafish

embryonic heart is the equivalent to a 3 week gestation human embryonic heart

Development of zebrafish

It takes about 72 hours for the zebrafish to complete embryonic development

Between the 10 hour period and the 14 hour period the beating heart becomes visible

After 35 hours the zebrafish will break out of its sac and begin to swim about

Testing My Hypothesis

The first part of either proving or disproving my hypothesis is to keep an accurate count of how many eggs there are› As time progresses, the eggs will become

fertilized and begin developing As this occurs it is important to keep track

of how many become fertilized and progress, how many are not fertilized, and how many die because of the teratogenic effects of SSRIs

Testing My Hypothesis (continued)

The other aspect of testing my hypothesis will be to monitor the beating heart of the fish

Since at around 10 hours the heart beat becomes visible under a microscope, any time after that I will be able to monitor which fish have normal rhythms and which are abnormal› The abnormal could be a sign that

there is a cardiovascular anomaly caused by a particular dosage

Resources

Congenital Cardiovascular Anomalies; http://www.merck.com/mmpe/sec19/ch287/ch287a.html

Baker, Fishman, Warren, Yellen; Defective “pacemaker” current (Ih) in a zebrafish mutant with a slow heart rate; http://www.pnas.org/content/94/9/4554.full?ck=nck#cited-by

Kimmel, Charles B, Stages of Embryonic Development of the Zebrafish