Process for regenerating neurons in the eye and brain identified

Date:
October 5, 2020
Source:
University of Notre Dame
Summary:
A team of researchers has identified networks of genes that
regulate the process responsible for determining whether neurons
will regenerate in certain animals, such as zebrafish.



FULL STORY ==========================================================================
The death of neurons, whether in the brain or the eye, can result
in a number of human neurodegenerative disorders, from blindness to
Parkinson's disease.

Current treatments for these disorders can only slow the progression of
the illness, because once a neuron dies, it cannot be replaced.


==========================================================================
Now, a team of researchers from the University of Notre Dame, Johns
Hopkins University, Ohio State University and the University of Florida
has identified networks of genes that regulate the process responsible
for determining whether neurons will regenerate in certain animals,
such as zebrafish.

"This study is proof of principle, showing that it is possible to
regenerate retinal neurons. We now believe the process for regenerating
neurons in the brain will be similar," said David Hyde, professor in
the Department of Biological Sciences at Notre Dame and co-author on
the study.

For the study, published in Science, the researchers mapped the genes of animals that have the ability to regenerate retinal neurons. For example,
when the retina of a zebrafish is damaged, cells called the Mu"ller
glia go through a process known as reprogramming. During reprogramming,
the Mu"ller glia cells will change their gene expression to become like progenitor cells, or cells that are used during early development of an organism. Therefore, these now progenitor-like cells can become any cell necessary to fix the damaged retina.

Like zebrafish, people also have Mu"ller glia cells. However, when the
human retina is damaged, the Mu"ller glia cells respond with gliosis,
a process that does not allow them to reprogram.

"After determining the varying animal processes for retina damage
recovery, we had to decipher if the process for reprogramming and gliosis
were similar.

Would the Mu"ller glia follow the same path in regenerating and non- regenerating animals or would the paths be completely different?" said
Hyde, who also serves as the Kenna Director of the Zebrafish Research
Center at Notre Dame. "This was really important, because if we want to be
able to use Mu"ller glia cells to regenerate retinal neurons in people,
we need to understand if it would be a matter of redirecting the current Mu"ller glia path or if it would require an entirely different process."
The research team found that the regeneration process only requires the organism to "turn back on" its early development processes. Additionally, researchers were able to show that during zebrafish regeneration,
Mu"ller glia also go through gliosis, meaning that organisms that are
able to regenerate retinal neurons do follow a similar path to animals
that cannot. While the network of genes in zebrafish was able to move
Mu"ller glia cells from gliosis into the reprogrammed state, the network
of genes in a mouse model blocked the Mu"ller glia from reprogramming.

From there, researchers were able to modify zebrafish Mu"ller glia cells
into a similar state that blocked reprogramming while also having a
mouse model regenerate some retinal neurons.

Next, the researchers will aim to identify the number of gene regulatory networks responsible for neuronal regeneration and exactly which genes
within the network are responsible for regulating regeneration.


========================================================================== Story Source: Materials provided by University_of_Notre_Dame. Original
written by Brandi Klingerman. Note: Content may be edited for style
and length.


========================================================================== Journal Reference:
1. Thanh Hoang, Jie Wang, Patrick Boyd, Fang Wang, Clayton Santiago,
Lizhi
Jiang, Sooyeon Yoo, Manuela Lahne, Levi J. Todd, Meng Jia, Cristian
Saez, Casey Keuthan, Isabella Palazzo, Natalie Squires, Warren
A. Campbell, Fatemeh Rajaii, Trisha Parayil, Vickie Trinh, Dong Won
Kim, Guohua Wang, Leah J. Campbell, John Ash, Andy J. Fischer,
David R. Hyde, Jiang Qian, Seth Blackshaw. Gene regulatory
networks controlling vertebrate retinal regeneration. Science,
2020; eabb8598 DOI: 10.1126/science.abb8598 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/10/201005122142.htm

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