高通量行为筛选介绍

PUBLICATIONS

Hypocretin/Orexin Overexpression Induces An Insomnia-Like Phenotype in Zebrafish

The Journal of Neuroscience

2009-12-20



Asmany as 10%of humans suffer chronic sleep disturbances, yet the geneticmechanisms that regulate sleep remainessentially unknown.It is therefore crucial to develop simple and cost-effective vertebratemodels to study the genetic regulation of sleep. The best characterized mammalian sleep/wake regulator is hypocretin/orexin (Hcrt), whose loss results in the sleep disorder narcolepsy and that has also been implicated in feeding behavior, energy homeostasis, thermoregulation, reward seeking, addiction, andmaternal behavior.Here we report that the expression pattern and axonal projections of embryonic and larval zebrafish Hcrt neurons are strikingly similar to those inmammals.We show that zebrafish larvae exhibit robust locomotive sleep/wake behaviors as early as the fifth day of development and that Hcrt overexpression promotes and consolidates wakefulness and inhibits rest. Similar to humans with insomnia, Hcrt-overexpressing larvae are hyperaroused and have dramatically reduced abilities to initiate andmaintain rest at night. Remarkably, Hcrt function is modulated by but does not require normal circadian oscillations in locomotor activity. Our zebrafish model of Hcrt overexpression indicates that the ancestral function of Hcrt is to promote locomotion and inhibit rest and will facilitate the discovery of neural circuits, genes, and drugs that regulate Hcrt function and sleep.

 

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Toxicity assessment of zebrafish following exposure to CdTe QDs

Journal of Hazardous Materials

2012-02-14


CdTe  quantum  dots  (QDs)  are  nanocrystals  of  unique  composition  and properties  that  have  found  many new  commercial  applications;  therefore,their  potential  toxicity  to  aquatic  organisms  has  become  a  hot research  topic.  The  lab  study  was  performed  to  determine  the developmental  and  behavioral  toxicities to  zebrafish  under  continuous exposure  to  low  concentrations  of  CdTe  QDs  (1–400  nM)  coated  with thioglycolic  acid  (TGA).  The  results  show:  (1)  the  120  h  LC50 of 185.9  nM,  (2)  the  lower  hatch  rate  and body length, more malformations, and less heart beat and swimming speed of the exposed zebrafish,(3) the brief burst and a higher basal swimming rate of the exposed zebrafish larvae during a rapidtransition from light-to-dark, and (4) the vascular hyperplasia, vascular bifurcation,vascular crossing and  turbulence  of  the  exposed  FLI-1  transgenic  zebrafish  larvae.

 

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Drug Screening to Treat Early-Onset Eye Diseases: Can Zebrafish Expedite the Discovery?

APJO

2012-10-23

Abstract
  The molecular basis of many early-onset eye diseases has been uncovered but the number
of available drug treatments for improving deteriorated vision is still scarce. Consequently, there
is a high demand for new drugs to treat these diseases. This review first provides a brief synopsis
of the utility of zebrafish model for screening drugs with vision benefits. In particular, visual-
motor response (VMR), the activity response of larvae to a change in light stimuli, is proposed to
serve as a simple and efficient tool for screening drugs that may improve vision in various
zebrafish visual mutants. The second part of the review discusses the identification of novel drug
candidates, with particular emphasis on naturally-derived chemicals including traditional
Chinese medicines (TCMs) and nutritional therapies on retinal degenerative diseases. Many of
these chemicals have been used in neuroprotection and/or have been consumed by many
populations for good health and vision; thus, the screening of these chemicals with various
zebrafish visual mutants would expedite the development of novel drugs for treating early-onset
eye diseases.