Monday, 18 May 2015

Astrocytes - “Stars of the brain”


Astrocytes, the most prevalent cell type in the brain, are increasingly recognised as playing a role in neurodegenerative diseases including Alzheimer’s disease. 


When you think of the brain and the cells that comprise it what do you think of? I’m guessing it’s neurons? Although it is true that there are billions of neurons in the brain and that they are responsible for executing everything we say and do there are another population of cells in the brain which for a long time have been overlooked – the glial cells.

Glia – sticky cells?

The word glia literally translates as ‘glue’ and these cells were first officially described back in 1846, when a German Anatomist called Rudolf Virchow described a connective substance that forms a ‘cement’ in the central nervous system (the brain and spinal cord) in which the neurons were embedded. For a long time after (and despite the work carried out by these early physiologists showing that these cells were not simply ‘glue’) most studies of the brain have focused on neurons with little regard to the potential role of glia in brain function or their contribution to disease. However in recent years there has been an increasing recognition that glia are crucial for healthy brain function and these cells are now stepping into the limelight and being given the recognition they deserve.

There are several different types of glia in the brain; 

oligodendrocytes which ensheath neurons enabling the fast transmission of neuronal signals; microglia are the defence cells of the brain, they scavenge for pathogens, damaged neurons and plaques; finally there are the astrocytes and these cells are the focus of this blog.

The stars of the brain

Astrocytes are typically star shaped, hence their name (Greek astron = star, and kytos = cell, hence a star-shaped cell). They were first officially described by Santiago Ramón y Cajal in 1909 (although the concept of glia and their morphology had already been around for about 60 years). Cajal won the Nobel Prize in Physiology in 1906 for his work on neurons but he also had a very keen interest in glia. The drawing below is one of Cajal’s early depictions of human astrocytes surrounding a blood vessel in the cerebral cortex of human brain.





Cajal’s drawing of fibrous astrocytes in human cerebral cortex
(Garcia-Lopez et al, 2010).
 In human brain it is estimated that there are 1.4 astrocytes for each neuron, and one single astrocyte can contact up to 1 million neuronal processes – amazing (and quite hard to imagine)! It is thought a lot of the complexity of human brain can be attributed to the evolution of astrocytes since human astrocytes are larger and more complex than those of other mammals. There are also distinct populations of astrocytes in human brain that are not found in the brains of other mammals. You can get an idea of the complexity of these cells in the image below from a researcher called Nancy Oberheim who also has a huge interest in these cells. The astrocytes can be seen in white, with neurons in red, you can see how complex (and pretty) the astrocytes are with long projections which will be extending to numerous (thousands and thousands) of neurons. 



Human astrocytes are shown in white, with neurons in red, from Oberheim et al., 2009.
Notice how the blood vessels are also white, this is because astrocytes
ensheath blood vessels so that they can regulate blood flow to the brain and
regulate the passage of substances in and out of the brain

Astrocytes are the workhorses of the brain

Astrocytes have numerous functions, a few of which are outlined below to highlight just how important these cells are for brain functioning! They are responsible for maintaining the barrier between the brain and the rest of the body (called the blood-brain barrier), which prevents the unregulated passage of substances into the brain. They are crucial in the formation and maintenance of synapses (the junctions between neurons), without these synapses neurons would not be able to signal to one another and they also regulate blood flow to the brain, increasing blood flow when there is a lot of brain activity and reducing it when brain activity decreases. In addition they are also crucial in repairing damage which occurs due to injury or disease.

Why all the fuss about these cells?

My specific interest in these cells relates to their emerging role in Alzheimer’s disease. In fact astrocytes are the focus of a number of researchers here at SITraN since there is evidence for astrocyte involvement in Motor Neurone Disease and Parkinson’s disease
as well as other diseases of the brain. My interest in astrocytes was sparked during my PhD at the Institute of Psychiatry where I discovered that astrocytes actually seemed to enhance the effect of toxic amyloid proteins.



Images from my PhD showing how astrocytes (in green) change in the presence of
toxic amyloid peptides which are present in Alzheimer’s brain.  Garwood et al., 2011

From London I moved here to SITraN as Prof. Stephen Wharton’s research group focused on astrocytes in ageing brain and Alzheimer’s disease – a perfect match! I have recently been awarded a research fellowship from the Alzheimer’s Society to continue investigating the role of astrocytes in Alzheimer’s disease, this will focus on how astrocytes respond to insulin and the role this plays in Alzheimer’s disease. This is interesting because there is a strong link between diabetes and Alzheimer’s disease and because evidence suggests the brain becomes resistant to insulin at the earliest stages of Alzheimer’s disease. In addition I am developing a system to grow astrocytes and neurons in a three-dimensional environment so it more closely mimics human brain.

I hope I have convinced you that astrocytes are very important cells that are deserving of our research time and do not simply function as ‘glue’. Below is one of my favourite cartoons from cartoon neuroscience which highlights just one of the roles of astrocytes! 


 Follow the Star!
Reproduced with permission from Immy Smith http://www.redbubble.com/people/immy


 By Dr Claire Garwood



I am an Alzheimer Society Research Fellow and my research focuses on understanding the role of astrocytes in the disease process.  You can follow me on my twitter account (@geekyclaire) or find me on Researchgate for a full list of up to date publications and research (www.researchgate.net).






Image references:
1. Garcia-Lopez P, Garcia-Marin V, Freire M (2010).
The histological slides and drawings of Cajal. Front. NeuroAnat. 4:9. 

2. Oberheim NA, Takano T, Han X, He W, Lin JH, Wang F, Xu Q, Wyatt JD, Pilcher W, Ojemann JG, Ransom BR, Goldman SA, Nedergaard M (2010).
Uniquely hominid features of adult human astrocytes. J Neurosci. 29(10):3276-87.

3. Garwood CJ, Pooler AM, Atherton J, Hanger DP, Noble W (2011).
Astrocytes are important mediators of Aβ-induced neurotoxicity and tau phosphorylation in primary culture. Cell Death Dis. 2;2:e167.
 
4. Cartoon reproduced with permission from Immy Smith http://www.redbubble.com/people/immy


 

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