Nav: Home

Hard times are coming: Brain tissue stiffness is crucial for neurogenesis

February 06, 2020

In mammalian adult brains, neural stem cells are only present in few specific parts, so called niches. Only these niches are capable of generating new neurons. For the first time, researchers defined the proteome of these niches, the entire set of expressed proteins, and compared it to other regions of the brain. The findings help to identify key regulators for neurogenesis, an important step towards activating neurogenesis after brain injuries.

What distinguishes neural stem cell niches from other parts of the brain? Why do only these niches contain neural stem cells and the rest of the brain does not? So far, we did not know what gives the niches their special function. Also, little was known about factors allowing the integration of new neurons into existing networks in the adult brain. A comparison of the proteome of neural stem cell niches and the region in which new neurons integrate with the remaining part of the brain, aimed to shed light about the unique niche environment allowing neurogenesis in the otherwise non-permissive adult mammalian brain.

Defining the niche characteristics

In a first step, Magdalena Götz and her team characterized the proteome of these specific brain regions. They used the largest neural stem cell niche in the subependymal zone of the brain and the olfactory bulb as this is the region where newly-generated neurons from the subependymal zone migrate, differentiate and integrate. They then compared this proteome to the cerebral cortex, an area where neither neurogenesis nor integration of new neurons occurs as in most parts of the adult mammalian brain. As a result, the team found that the proteome of the neurogenic niche evokes a niche-specific extracellular matrix architecture. One of the most important characteristics was the high solubility of the extracellular matrix. Other characteristic proteins however, such as those of the multifunctional enzyme transglutaminase 2, are hardly soluble meaning strongly cross-linked. Using pharmacological inhibitors as well as genetic experiments, the team was able to show that transglutaminase 2 is crucial for the regulation of neurogenesis. Furthermore, due to its cross-linking properties, the enzyme may contribute to the unique stiffness of the neural stem cell niche in otherwise soft brain tissue.

Turning the injured brain region into a neural stem cell niche

Having established the differences between the proteome of a neurogenic and a non-neurogenic site is a key step. It could help to find ways to convert the one to the other. Equally important for future cell replacement therapies is the generation of a beneficial environment for the integration of new neurons in the cerebral cortex by activating factors from the olfactory bulb, an area where new neurons are constantly being integrated. Next, the researchers want to compare these proteomes to the environment after brain injury. Their aim is to create new neurons after brain injury by turning the injured region into a neurogenic stem cell niche. Injured tissue demonstrates alternative phenotypes, that may create additional barriers for activating neurogenesis: "One of our collaborators at the University of Cambridge showed that scar tissue in the brain is particularly soft - a trait that is hostile to the function of neurogenesis. Overcoming this hurdle and generating a beneficial environment for repair will be the next steps of our research", says Götz.
-end-
Magdalena Götz is Head of the Division Physiological Genomics at the Biomedical Center of the Ludwig-Maximilians-University Munich and leads the Institute of Stem Cell Research at Helmholtz Zentrum München.

Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes, allergies and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,500 staff members. It is a member of the Helmholtz Association, a community of 19 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. http://www.helmholtz-muenchen.de/en

The Institute of Stem Cell Research (ISF) investigates the basic molecular and cellular mechanisms of stem cell maintenance and differentiation. From that, the ISF then develops approaches in order to replace defect cell types, either by activating resting stem cells or by re-programming other existing cell types to repair themselves. The aim of these approaches is to stimulate the regrowth of damaged, pathologically changed or destroyed tissue. http://www.helmholtz-muenchen.de/en/isf

Helmholtz Zentrum München - German Research Center for Environmental Health

Related Neurons Articles:

Paying attention to the neurons behind our alertness
The neurons of layer 6 - the deepest layer of the cortex - were examined by researchers from the Okinawa Institute of Science and Technology Graduate University to uncover how they react to sensory stimulation in different behavioral states.
Trying to listen to the signal from neurons
Toyohashi University of Technology has developed a coaxial cable-inspired needle-electrode.
A mechanical way to stimulate neurons
Magnetic nanodiscs can be activated by an external magnetic field, providing a research tool for studying neural responses.
Extraordinary regeneration of neurons in zebrafish
Biologists from the University of Bayreuth have discovered a uniquely rapid form of regeneration in injured neurons and their function in the central nervous system of zebrafish.
Dopamine neurons mull over your options
Researchers at the University of Tsukuba have found that dopamine neurons in the brain can represent the decision-making process when making economic choices.
Neurons thrive even when malnourished
When animal, insect or human embryos grow in a malnourished environment, their developing nervous systems get first pick of any available nutrients so that new neurons can be made.
The first 3D map of the heart's neurons
An interdisciplinary research team establishes a new technological pipeline to build a 3D map of the neurons in the heart, revealing foundational insight into their role in heart attacks and other cardiac conditions.
Mapping the neurons of the rat heart in 3D
A team of researchers has developed a virtual 3D heart, digitally showcasing the heart's unique network of neurons for the first time.
How to put neurons into cages
Football-shaped microscale cages have been created using special laser technologies.
A molecule that directs neurons
A research team coordinated by the University of Trento studied a mass of brain cells, the habenula, linked to disorders like autism, schizophrenia and depression.
More Neurons News and Neurons Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Warped Reality
False information on the internet makes it harder and harder to know what's true, and the consequences have been devastating. This hour, TED speakers explore ideas around technology and deception. Guests include law professor Danielle Citron, journalist Andrew Marantz, and computer scientist Joy Buolamwini.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at Radiolab.org/donate.     You can read The Transition Integrity Project's report here.