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Salamanders can regenerate their brains

To summarize: Salamanders have the ability to regenerate brain regions after injury. The researchers mapped the cell types and genes associated with neurodegeneration in the salamander brain, finding some similarities in the human brain. The findings could pave the way for new neurodegenerative therapies.

resource: conversation

Salamander (Mexican mushroom) is an aquatic salamander known for its ability to regenerate the spinal cord, heart and limbs. These amphibians also readily make new neurons throughout their lives. In 1964, researchers observed that adult salamanders could regenerate parts of their brains, even when most of the parts were completely removed. But one study found that salamander brain regeneration has a limited ability to rebuild its original tissue structure.

So how do salamanders regenerate their brains perfectly after injury?

As researchers studying regeneration at the cellular level, my colleagues and I in the Treutlein lab at ETH Zurich and the Tanaka lab at the Institute of Molecular Pathology in Vienna wondered whether salamanders were able to regenerate all the different types of cells in their brains, including A connection that connects one brain area to another.

In our recently published study, we created an atlas of the cells that make up part of the salamander’s brain, revealing how it regenerates and brain evolution across species.

Why look at cells?

Different cell types have different functions. They are able to specialize in certain roles because each of them expresses different genes. Understanding what types of cells are in the brain and what they do can help shed light on the overall picture of how the brain works. It also allows researchers to compare evolution and try to find biological trends across species.

One way to learn which cells are expressing which genes is to use a technique called single-cell RNA sequencing (scRNA-seq). The tool allows researchers to count the number of active genes in each cell of a given sample. This provides a “snapshot” of the activity each cell was performing at the time of collection.

Credit: UCSF

The tool helps to understand the types of cells present in the brains of animals. Scientists have used scRNA-seq in fish, reptiles, mice and even humans. But a major piece of the brain evolution puzzle has been lost: amphibians.

Mapping axonal brains

Our team decided to focus on the telencephalon of the salamander. In humans, the telencephalon is the largest part of the brain and contains an area called the neocortex, which plays a key role in animal behavior and cognition.

During recent evolution, the neocortex has grown substantially in size compared to other brain regions. Likewise, the cell types that make up the telencephalon are highly diverse and complex over time, making this region an interesting area of ​​study.

We used scRNA-seq to identify the different types of cells that make up the salamander telencephalon, including different types of neurons and progenitor cells, or cells that can divide into more of themselves or become other cell types.

We determined which genes are active when progenitor cells become neurons and found that many genes pass through an intermediate cell type called neuroblasts — previously not known to exist in salamanders — before becoming mature neurons.

Credit: TED Ed

We then tested the salamander’s regeneration by removing part of its telencephalon. Using a specialized scRNA-seq method, we were able to capture and sequence all new cells at various stages of regeneration from 1 to 12 weeks after injury. Ultimately, we found that all removed cell types were fully recovered.

We observed that brain regeneration occurs in three main stages. The first stage begins with a rapid increase in the number of progenitor cells, a small fraction of which activate the wound healing process. In the second stage, progenitor cells begin to differentiate into neuroblasts. Finally, in the third stage, neuroblasts differentiate into the same type of neurons that were initially lost.

Surprisingly, we also observed that the severed neuronal connections between the resection area and the rest of the brain had rewired. This rewiring indicates that the regeneration area has also regained its original function.

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Amphibians and the human brain

Adding amphibians to the evolutionary puzzle allows researchers to infer how the brain and its cell types have changed over time, as well as the mechanisms behind regeneration.

When we compared our salamander data with other species, we found that cells in its telencephalon behaved well with the mammalian hippocampus (a region of the brain involved in memory formation) and the olfactory cortex (a region of the brain involved in sensation). strong similarity. smell. We even found that one axonal cell type shares some similarities with the neocortex, the brain region in humans known for perception, thinking, and spatial reasoning.

These similarities suggest that these regions of the brain may be evolutionarily conserved or remain comparable over evolution, and that the mammalian neocortex may have an ancestral cell type in the amphibian telencephalon.

This shows a salamander.
Salamanders are model organisms that researchers use to study a variety of biological topics.Image is in the public domain

While our research sheds light on the process of brain regeneration, including which genes are involved and how cells eventually become neurons, we still don’t know what external signals initiate this process. Furthermore, we do not know whether the processes we identified still apply to animals that evolved later, such as mice or humans.

But we’re not alone in solving the brain evolution puzzle. The Tosches lab at Columbia University explored the diversity of cell types in another salamander, side earwhile collaborators from the Fei lab at the Guangdong Academy of Medical Sciences in China and the life sciences company BGI have explored how cell types are spatially arranged in the salamander forebrain.

Identifying all the cell types in the salamander brain could also help pave the way for innovative research in regenerative medicine. The brains of mice and humans have largely lost their ability to repair or regenerate themselves. Medical intervention for severe brain injury currently focuses on drugs and stem cell therapy to promote or facilitate repair.

Examining the genes and cell types that enable the salamander to achieve near-perfect regeneration may be the key to improving the treatment of severe injuries and unlocking the regenerative potential in humans.

About this neuroregeneration and evolutionary neuroscience research news

author: Ashley Maynard
resource: conversation
touch: Ashley Maynard – Conversation
picture: Image is in the public domain

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