How Rogue Astrocytes Cause Neurodegeneration

 

You have a number of different cells throughout your body, all of which perform different functions or provide support. One extremely interesting type are astrocytes, star-shaped glial cells that are largely found throughout your central nervous system. They play a role in metabolic processes, inflammatory signaling, regulating blood flow, and managing brain circuit connectivity. But what happens when they go rogue? According to a study from the New York Stem Cell Foundation (NYSCF) Research Institute, they make contribute to neurodegeneration in conditions like multiple sclerosis, Alzheimer’s disease, and Parkinson’s disease. Check out the full study in Neuron to learn more about how researchers discovered the CD49f marker for astrocytes and what this told them about disease mechanisms.

What are Astrocytes?

As stated before, astrocytes are a type of glial cell. Glia make up a huge number of cells in the central nervous system. A description in Neuroscience explains glia as:

not [participating] directly in synaptic interactions and electrical signaling, although their supportive functions help define synaptic contacts and maintain the signaling abilities of neurons. Glia are more numerous than nerve cells in the brain.

There are 3 main types of glial cells: astrocytes, microglial cells, and oligodendrocytes. According to Tempo Biosciences, astrocytes support brain and neuronal function in multiple ways:

  • Maintaining brain homeostasis
  • Supporting neuronal metabolic processes
  • Controlling neuronal cell development, plasticity, and synaptogenesis
  • Regulating the sleep cycle
  • Filling spaces left by damaged or degenerated neurons
  • Acting as an immune support
  • Regulating water movement

Because human astrocytes and animal astrocytes aren’t the same, prior studies on mice models do not give researchers a full or completely relevant understanding of the cells’ intersection with neurodegenerative conditions.

As a result, NYSCF researchers created a plan: using stem cells to develop human astrocytes. This would allow them to both:

  • Learn the relationship to neurodegeneration
  • Develop drug therapy ideas to target rogue or malfunctioning astrocytes

The NYSCF Study

In prior research, the NYSCF team created a distinct set of protocols regarding how to convert stem cells into glial cells. Through this, they were able to identify CD49f, an astrocyte protein marker. By recognizing this marker, researchers could specifically isolate astrocytes from other cells.

Next, researchers determined that CD49f could be found in both healthy brain tissue and diseased brain tissue. After this, they began to look into how and why astrocytes went rogue in disease states.

Dr. Shane Liddelow, PhD, collaborated on the study. He noted that, in mice models of neurodegenerative diseases:

Astrocytes in inflammatory environments take on a reactive state, usually attacking neurons rather than supporting them.

But did this also happen in humans? To find out, the NYSCF team created a pro-inflammatory environment, similar to the brain of patients with neurodegenerative diseases. After collecting the byproducts from stem-cell-derived astrocytes, and exposing healthy neurons to these byproducts, researchers witnessed neuronal death.

Additionally, astrocytes experienced their own issues:

  • Losing their shape
  • Misfiring
  • Not taking on much glutamate
  • Failing to support neuronal maturation

Researchers hope that these findings will allow for the development of more targeted therapies for patients with neurodegenerative conditions.

Learn more about this here.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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