Q 1 & 2: What Are Astrocytes? What Do Astrocytes Do?

Astrocytes or astroglia are the largest and most numerous types of glial cells (see below) in the Central Nervous System (CNS). There are various subtypes of astrocytes within the different regions of the brain that show a heterogeneity of shape and function.  Astrocytes usually have a star-shaped structure created by processes or tendrils that extend from the cell and can be long, short, straight, crooked, highly-branched, or more simple in shape. Numerous subtypes have been described in humans, including fibrous, protoplasmic, Layer-1, interlaminar and varicose projection astrocytes. The unique functions of each and their role in disease is currently the subject of much research.

The broad role of astrocytes is to maintain brain homeostasis and neuronal metabolism. It’s hypothesized that the “star-shape” supports the neurons and creates the microarchitecture of the brain parenchyma illustrating that form-follows-function rule seen across biology. They provide neurons with mechanical support, control neuronal cell development, plasticity and synaptogenesis, release nutritional and energy substrates like glucose and lactate and play a role in neurotransmission, vasomodulation and repair. Astrocytes also maintain and control the concentrations of ions, neurotransmitters and metabolites and regulate water movements. More recently, it has been suggested that astrocytes play a role in the regulation of the sleep/wake cycle. Lastly, astrocytes play a role in immunodefense. No wonder these cells are so heterogeneous, they play a role in almost everything!

Jargon Alert!

“Astro-” means star
“-cyte” means cell
“Glia” means glue

Quick Fact!

Question: What are glial cells?

Answer: Supportive “glue” cells that provide a structure to support and insulate neurons. They cannot conduct electrical impulses and they’re the most abundant cell type in the CNS. Types of glial cells include: oligodendrocytes, astrocytes, ependymal cells, Schwann cells, microglia, and satellite cells.

Q 3: What Is the Immune Role of Astrocytes?

Like many cells with an immune function, astrocytes can either be pro- or anti-inflammatory. This dichotomy allows them to contribute to the neuroimmune state of the brain and may play a key role in disease prevention and treatment. Whether astrocytes promote or suppress an inflammatory response seems to be largely decided by the microenvironment in which they exist and receive signal from.

The immune roles of astrocytes include:

  • Antigen-presentation to T cells.
  • Reprogramming T cells to a pro- or anti-inflammatory phenotype.
  • Induce T cell apoptosis.
  • Secrete pro- or anti-inflammatory mediators.
  • Detection of pathogens through an array of receptors, including Toll-like receptors, nucleotide-binding oligomerization domains, double-stranded RNA-dependent protein kinase, scavenger receptors, mannose receptor and components of the complement system.
  • Secretion of soluble mediators, such as CXCL10, CCL2, interleukin-6 and BAFF, which have an impact on both innate and adaptive immune responses.

Q 4: What Is the Role of Astrocytes in Glial Scar Formation?

Rather than forming a fibrous scar in response to injury like other parts of the body, the brain forms a glial scar composed of reactive astrocytes, a process called astrogliosis. This process is seen in infection, neurodegenerative diseases, infarction, brain cancer, acute traumatic brain injury and demyelinating diseases.

Q 5: How Do Astrocytes Play a Role in Neurodegenerative Diseases Like Alzheimer’s Disease?

Historically, it was thought that the overactivity of astrocytes in Alzheimer’s Disease was exacerbating the disease state of patients and contributing to the deteriorating of the nervous components of the body. Key to this was the finding of reactive astrocytes intricately associated with amyloid plaques. More recently, mouse studies have called this into question as reducing the number of astrocytes appeared to worsen the disease not ameliorate it. Current thinking is that the activated state of astrocytes in neurodegenerative disease may be less offensive and more defensive a response that promotes a neuroprotective response. The formation of glial scars in neurodegenerative disease may be to isolate the site of injury and promote healing. Where this response seems to sour is when it reaches such a point that it’s damaging tissue resulting in an endless cycle of damage leading to inflammation leading to damage and repeat. In the later stages of neurodegenerative disease, astrocytes seem to become dysfunctional and less able to carry out their normal functions, suggesting that disease progression may be linked to how long astrocytes can carry out their vital duties before becoming overly distracted by nearby neural damage. As in the case with many cells of the body, the exact role of astrocytes in neurodegeneration seems to be dependent on nuances the exact nature of which requires more research to define.

Q 6: How Are Astrocytes Detected and Identified?

Astrocytes can be selectively stained for study using unique biomarkers found intra- or extracellularly.

The list of markers for astrocytes includes:

  • ​​Glial fibrillary acidic protein (GFAP) – an intermediate filament protein of the cell cytoskeleton that is responsible for the star-shape of the astrocyte. Mutations in GFAP are implicated in Alzheimer’s Disease.
  • S100 beta –  a calcium-binding protein involved in the regulation of cell cycle progression and differentiation. This protein is also found in primarily in astrocytes encapsulating brain capillaries. It is also found in oligodendrocyte precursor cells (OPCs) so co-labelling is recommended.
  • Excitatory amino acid transporters 1 and 2 (EAAT1 and 2) – Na+-dependent glutamate transporters that remove excess glutamate from the extracellular space.
  • Aldehyde dehydrogenase 1 family, member L1 (ALDH1L1) – a catalytic enzyme involved in neural tube development.

Q 7: What Are Astrocytomas?

Astrocytomas are tumors derived from astrocytes. They can occur in most major parts of the CNS including the brain stem, spinal cord and the central parts of the brain. Tumors are graded along a scale of I-IV based on how likely they are to spread and the rate at which they’ll grow. More information can be found on the American Brain Tumor Association’s site.

Conclusion

Astrocytes are extremely heterogeneous glial cells with diverse, critical functions in the CNS. These include homoeostasis, defence and regeneration. While their role in neurodegenerative disease was thought to be deleterious, it is now thought to be far more complex and may depend on the stage of the disease as well as a variety of other factors like the part of the CNS in which the astrocyte exists and the microenvironment in which the astrocyte is found. As researchers continue “star-gazing” and learning more about these cells, their potential as targets in neurodegenerative disease is fast becoming a very interesting area and so hopefully clinical trials targeting these cells are not too far into the future.


Article by Olwen Reina. Contact Olwen at olwen@tempobioscience.com.