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Israeli Scientists Use Zebrafish Model To Accelerate Medical Cannabis Strain Development

October 20, 2020 in General News

Two Israeli cannabis companies have teamed up to use a zebrafish model to assess the therapeutic potential for different cannabis strains. In this article I will give some background information about the two companies who developed this new test model. I will cite the zebrafish sleep study, explain why the zebrafish model was chosen and discuss the importance of sleep and its implications for humans.

Camanex and Canonic Collaboration

Two Israeli-based companies, Camanex and Canonic, collaborated in developing the zebrafish test model. Camanex is the applied science subsidiary for cannabis of MIGAL Galilee Research Institute. Canonic, a subsidiary of Evogene, focuses on the development of medical cannabis products. Evogene’s plant genome information technology gives targeted cannabis strains the capability to treat specific medical conditions.

Their collaboration starts in the laboratory and ends with varieties of cultivars in their greenhouses. With their combined areas of expertise, the expected outcome is the development of strains that have explicit capabilities for an assortment of medication indications and the potential for commercial success.

Canonic Press Release

In November, 2019, in a press release, Canonic announced the implementation of its cultivation and breeding program of cannabis strains with unique genome profiles for the development of medical cannabis products. This will be achieved by doing the following:

  • Importing cannabis lines from different parts of the world with extensive genetic diversity
  • Establishing R & D facilities dedicated entirely to cannabis cultivation which include greenhouses, a molecular lab and tissue culture rooms
  • Receiving the necessary regulatory approvals from the Israel Medical Cannabis Agency (IMCA)

Why Zebrafish?

Testing specific strains of cannabis for its therapeutic potential using mice or humans is a slow, time-consuming process. Based on sleep research on zebrafish conducted by researchers at Bar-Ilan University in Israel, cannabis researchers realized that zebrafish made the perfect test model. They have a brain structure similar but simpler than that of humans. Their brain activity is easier to monitor because they lack a skull.

Using the zebrafish model allowed researchers to first assess an accurate, rapid preliminary sorting of cannabis strains for their potential treatment of specific medical conditions. Next, they identified which compound was responsible for each therapeutic effect. The conditions that the system has already identified include the following:

  • Sleep problems
  • Seizures
  • Parkinson’s disease
  • Pain

Additional indications to be studied include autism and anxiety.

Zebrafish Sleep Study

All living beings require a significant amount of sleep. For those creatures that live in the wild, the time they spend sleeping leaves them vulnerable and at risk for attack by predators. This suggests that the importance of sleep outweighs the risk of death.

Here is how to tell when a zebrafish is asleep:

  • It stops swimming for at least six seconds
  • It remains motionless either at the bottom or on the surface of the water
  • It becomes less sensitive to external stimulation

The study, Sleep Increases Chromosome Dynamics To Enable Reduction of Accumulating DNA Damage in Single Neurons, published on March 5, 2019 in Nature Communications, gave researchers insight into why sleep is so crucial for survival.

To understand the importance of sleep, researchers used new 3D time-lapse imaging techniques to scan the chromosome activity of the cells of sleeping zebrafish. They were able to monitor the movement and dynamics of the zebrafish chromosomes during their periods of wakefulness and sleep. They discovered the following information:

  • When the fish are asleep, their chromosomes move twice as much compared to when they are awake. This was not at all what they expected.
  • The use of the chromosome and dynamics technique allowed researchers to identify single sleeping cells.
  • Single neurons require sleep in order to successfully carry out their nuclear maintenance.
  • Nuclear maintenance is a crucial process that repairs the damage to DNA that takes place in all cells. During wakefulness, when chromosome movement is slow, the damage to DNA piles up to the point of reaching dangerous levels. If the fish are not allowed to sleep, more DNA damage occurs.
  • After the fish have slept, the DNA damage is repaired and the neurons return to their normal states.

Studies using zebrafish have given researchers new understanding into the importance of the systems that modulate sleep and wakefulness. These include:

  • The role of melatonin and its receptors
  • The regulation of sleep through homeostatic and circadian mechanisms
  • The way melatonin interacts with the hypocretin/orexin system; hypothalmic neuropeptides that play an important role in the regulation of sleep and arousal states.

One of the study’s co-authors, brain scientist Professor Lior Appelbaum, makes the following analogy:
“It’s like potholes in the road. Roads accumulate wear and tear, especially during daytime rush hours, and it is most convenient and efficient to fix them at night, when there is light traffic.”

Far- Reaching Study Implications for Humans
Researchers now recognize that many neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis (ALS) involve symptoms of sleep disturbances. It seems logical to conclude that lack of good sleep can eventually harm the brain. While you can easily recover from an occasional missed night’s sleep, long-term sleep deprivation can have mental, physical and emotional repercussions.

Researchers are not ready to make a direct correlation between lack of sleep and the development of neurodegenerative diseases. However, they acknowledge that the next step is to investigate more fully its importance in mammals. The research supports the need for sleep. It is the first time that photos of the brain have been captured that illustrate the difference in the brain neurons during wakefulness and sleep.

Sources:
israel21c.org, Sleep Vital To Repair DNA Damage, Israeli Study Finds, Naama Barak, March 6, 2019
evogene.com, Canonic Announces Initiation of Cultivation and Breeding of Cannabis Varieties with Unique Genomic Profiles for the Development of Medical Cannabis Products, November 19, 2019
migal.org.il, Camanex
nature.com, Sleep Increases Chromosome Dynamics To Enable Reduction of Accumulating DNA Damage in Single Neurons, March 5, 2019
israeli21c.org, Zebrafish Help Scientists Speed Up Tests For Medical Cannabis Strains, Abigail Klein Leichman, Sept. 9, 2020

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