Brain cells need microRNA to survive

Neurons that cannot produce microRNAs - tiny strands of RNA that regulate the expression of genes - die slowly in a manner similar to that seen in degenerative brain diseases such as Alzheimer's and Parkinson's

Brain cells need many things to survive. Now add microRNA to the list. New research from Rockefeller University shows that neurons that cannot produce microRNAs - tiny strands of RNA that regulate the expression of genes - die slowly in a manner similar to that seen in degenerative brain diseases such as Alzheimer's and Parkinson's.
In a report published on July 2 in the online edition of the Journal of Experimental Medicine, the researchers claim that although so far no direct link has been found between microRNAs and any diseases, the study they did in mice shows that these tiny RNA segments are necessary for the survival of mature neurons .
"This study shows that microRNAs are necessary for certain neurons to function and survive, and this means that they are most likely also involved in the survival of other neurons," says the senior researcher involved in the study, Paul Gringrad, head of the Laboratory for Molecular and Cellular Research of Neurons. "This leads us to the assumption that irregularities in the expression of microRNA may cause the disease, or affect the course of its progression."
The researchers found that mice engineered so that microRNAs would not be expressed in their cortical neurons suffered a slow decline in function after birth, which was due to the death of the neurons known as Forking cells. Because this area of ​​the brain helps control motor function, the mice lacking functioning Forking cells were unable to walk.
Because the use of these specific cells provided a model system for testing microRNA deletion, the results could likely be applicable to other types of neurons, such as those involved in memory and higher-order thinking, says the study's lead author, Ann Schaefer, a postdoc researcher. A colleague in Gringrad's laboratory. These findings are "exciting", she says. "Previously, there was no proof that mature neurons, which have already been sorted and are no longer dividing, would need microRNA for function and survival."
Since their discovery in 1993, it has become clear that microRNAs are important regulators of gene expression, but mainly in cells that are still developing. Neurons in the process of differentiation express a wide variety of microRNAs, and their development stops if the microRNAs cannot function. Although it was known that these pieces of RNA were also found in mature cells, it was not known if they had any role in the life of these mature cells.
To find out what their role is, the research team bred three types of mice. The first type, engineered by Donal O'Carroll, who co-authored the study, is known as the "conditional Dicer mouse". It allows researchers to delete a gene called Dicer, whose protein is required to produce microRNA. The mice of the first type were hybridized with mice of the second type, engineered by researchers at the University of Hong Kong. The second type of mice produced a protein called Cre-recombinase that silences the Dicer gene in mature Purking cells (after birth). The offspring of crossing the first two types were in turn crossed with a third type of mice, engineered to produce green fluorescent proteins when their dicer gene is deleted. In this way, the researchers could trace the deletion of the Dicer gene and then test for the presence of various microRNAs normally found in the adult brain.
They found that some microRNAs were deleted immediately while others took longer, during which time the cells were fairly stable, but degenerated slowly. In the end, "the mice showed signs similar to those observed in people with neurodegenerative syndromes of the brain, and at the end of 18 weeks, almost all the Forking cells had died," Schaefer said.
The question of whether specific microRNA changes contribute to degenerative syndromes of the human brain remains open, Schaefer said, but researchers now have ways to test it experimentally. They can compare the expressions of microRNAs in healthy and diseased human brains, and they can delete specific microRNAs in the mouse model to deduce which ones play more important roles. "We now have a program to identify genes that may be involved in brain degeneration processes, which is very important and exciting," says Greengard.

For the original news, based on a message from Uni Rockefeller