Tiny transparent zebra fish yields big clue to black box of Alzheimer’s disease

The PR folks at the Flanders Institute for Biotechnology in Belgium produced an unusual press release to describe recent work there published in Developmental Cell. They devoted the first half to the marvels of their animal model the zebra fish.

zebrafish1For those who have only seen these nearly transparent little guys in a home aquarium the story provides a nice explanation for why they are such popular lab models. It is not unusual to walk into a lab with dozens of small fish tanks holding thousands of zebra fish. A couple key reasons: their DNA matches 90 percent of ours and the guys reproduce quickly, just three months after birth.

Nerve stem cells, key players to brain development in the embryo, become few in number in adults. More important, those few we have left seem to be less active when we need them most, when Alzheimer’s disease or other neurodegenerative disease destroys some of our existing nerves. Evgenia Salta at the Institute used the fish to try to discern why.

We have known for some time that the genes in a pathway known as Notch regulate the ability of nerve stem cells to mature into adult nerves. But we don’t know why that goes awry in disease. She focused on a genetic regulatory molecule called a microRNA that is known to be in abnormally low supply in cells from patients with Alzheimer’s.

When they manipulated the fish to lower the levels of this microRNA, the nerve stem cells in the fish failed to mature properly into nerve cells. In the press release published on ScienceDaily Salta is quoted saying:

“To our surprise, the reduced activity of miRNS-132 in the zebra fish blocks the further ripening of the stem cell into nerves cells. This new knowledge about the molecular signaling pathway that underlies this process gives us an insight into the exact blocking mechanism. Thanks to this work in zebra fish, we can now examine in detail what exactly goes wrong in the brains of patients with Alzheimer’s disease.”

You can read about CIRMM-funded projects seeking solutions to Alzheimer’s Disease on our fact sheet.

Don Gibbons

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