When neuroscience is the topic, neurons tend to take all of the spotlight due to their association with information processing. However, glial cells have also been shown to contribute to higher functions such as the modulation of nociception, the sensation of pain, in addition to performing supporting roles (Spitzer, Agathou and Karadottir, 2013). Due to their involvement with nociception, glial cells have been looked at as a possible drug target in patients with chronic pain.
The association between glial activation and chronic pain has been confirmed by numerous studies. Loggia et al. (2015) recently showed evidence for brain glial activation in chronic pain patients using positron emission tomography-magnetic resonance imaging (PET-MRI). Increased brain levels of translocator protein (TSPO), a marker for glial activation, were observed in patients with chronic low back pain (Figure 1). Due to such evidence, targeting glial cells (as drug targets) has developed into a valid consideration for combatting chronic pain (Watkins and Maier, 2003; Romero-Sandoval, Horvath and DeLeo, 2008).
One of these targets–astroglia, macroglial cells also known as astrocytes–have supporting functions in the blood-brain barrier where they aid endothelial cells in forming the blood-brain barrier structure (Nicholls et al., 2012). Following spinal cord injury (SCI), astroglia are involved in the chronic dysregulation of glutamate uptake, which leads to various forms of neuropathic pain (Falnikar et al., 2016). However, upon astrocytic over-expression of glutamate transporter GLT-1, functional glutamate levels are restored, making astrocytes a promising target in the treatment of chronic pain involving SCI (Figure 2). Fortunately, the drug propentofylline has been shown to enhance expression of GLT-1 in vitro and in vivo, giving hope to SCI patients in terms of treatment options (Romero-Sandoval, Horvath and DeLeo, 2008).
The association between glial cells and the modulation of nociception has been well established. In addition, research supporting drug targets that attenuate chronic pain due to glial involvement is underway. Studies of specific targets such as glial subtypes and receptor proteins involved in glial-neuronal interactions should further elucidate the mechanistic nature of targeting glia. It is true that we often do not notice what is immediate, proximate, or abundant. Taking the example of glia, let us not forget to notice these “other” cells ever again.
References
Falnikar, A., Hala, T.J., Poulsen, D.J. and Lepore, A.C., 2016. GLT1 overexpression reverses established neuropathic pain-related behavior and attenuates chronic dorsal horn neuron activation following cervical spinal cord injury. Glia, [e-journal] 64(3), pp.396–406. http://dx.doi.org/10.1002/glia.22936.
Loggia, M.L., Chonde, D.B., Akeju, O., Arabasz, G., Catana, C., Edwards, R.R., Hill, E., Hsu, S., Izquierdo-Garcia, D., Ji, R.-R., Riley, M., Wasan, A.D., Zürcher, N.R., Albrecht, D.S., Vangel, M.G., Rosen, B.R., Napadow, V. and Hooker, J.M., 2015. Evidence for brain glial activation in chronic pain patients. Brain, [e-journal] 138(3), pp.604–615. http://dx.doi.org/10.1093/brain/awu377.
Nicholls, J.G., Martin, A.R., Fuchs, P.A., Brown, D.A., Diamond, M.E. and Weisblat, D.A., 2012. From neuron to brain. 5th ed. Sunderland, Mass: Sinauer Associates.
Romero-Sandoval, E.A., Horvath, R.J. and DeLeo, J.A., 2008. Neuroimmune interactions and pain: Focus on glial-modulating targets. Current opinion in investigational drugs, [e-journal] 9(7), pp.726–734. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2696046/.
Spitzer, S., Agathou, S. and Karadottir, R.T., 2013. Clever glia. Stem Cell Research & Therapy, [e-journal] 4(4), p.100. http://dx.doi.org/10.1186/scrt311.
Watkins, L.R. and Maier, S.F., 2003. GLIA: A novel drug discovery target for clinical pain. Nature Reviews Drug Discovery, [e-journal] 2(12), pp.973–985. http://dx.doi.org/10.1038/nrd1251.
Wen, Y.-R., Tan, P.-H., Cheng, J.-K., Liu, Y.-C. and Ji, R.-R., 2011. Role of microglia in neuropathic pain, postoperative pain, andmorphine tolerance. Journal of the Formosan Medical Association, [e-journal] 110(8), pp.487–494. http://dx.doi.org/10.1016/S0929-6646(11)60074-0.
Comments
15 Responses to “Glia: the “other” cells in neuroscience”
Hi everyone,
I found it really interesting how Neuroscience and Drug Discovery can intersect when looking at some recent scientific developments involving an often forgotten part of the brain, the glia (a.k.a. glial cells) and their ability to modulate pain when acting as a drug target. I hope you enjoy the read!
Sincerely,
Aakanx
Hi Aakanx,
I really enjoyed your blog post! I really liked how you brought together what we are learning in neuroscience and drug discovery. I just have a few suggestions:
1. I had a bit of trouble understanding the purpose of your second paragraph. You could maybe consider moving it into your first paragraph write when you introduce glial cells. I am not sure if it does but possibly tie the fact that glial cells contribute to neuronal information processing to nociception.
2. I think it may be beneficial if you could possibly expand on how targeting those potential drug targets in Figure 2 may help with chronic pain in terms of the pathways they are responsible for.
Thanks for a great read!
Dominique Tertigas
Hi Dominique,
Thanks for your comments! I merged the first and second paragraphs to have a single introductory idea, and expanded on the drug targets section, focusing on targeting astrocytes, as per your suggestions.
Thanks,
Aakanx
Hi Aakanx,
What an interesting post! Glial cells are often overlooked for their importance. I think overall you did a good job presenting research related to pain. Below are a few comments.
1. As much as we like to consider neuroscience to be the study of the brain there are many other associated organs/pathways involved so your title may be slightly misleading. Also as your post is primarily talking about pain and nociception it would be nice if the title was representative of that.
2. I am not entirely sure what you mean by glial cells making up “90 % of the brain”. Is this by volume, by area? I think a citation is also needed.
3. In your third paragraph, you state that some studies have investigated the relationship between pain and glial cells. By citing 4 articles it gives the impression that these are the only 4 articles that looked into the relationship. If this is not the case I would recommend not citing any (as you do not bring them up again).
Otherwise a great start! I hope these comments are useful.
—
Sloane Kowal
Hi Sloane,
I have changed the title such that it does not imply glia are only present in the brain. However, I would like to keep the title a little broader; so, I will leave pain out of the title. I see the issue with glia making up “90 % of the brain” (this was referring to 90 % of cells in the brain). I have removed it completely as I realized keeping it would contradict your first point about implying neuroscience is “the study of the brain.” I also omitted the four citations in sequence as there have been more than four studies that looked into the relationship. Thank you so much for your comments – they were indeed very useful!
Thanks,
Aakanx
Hi Aakanx,
Interesting blog post, I actually had no idea that glial cells were overlooked. It was nice how you brought to light that glia can be used for fashioning new drugs. I do have a few suggestions:
1. I feel as though your title is misleading to what your content is about. You briefly touch upon the fact that glial cells are forgotten, and you focus more on how they can be targeted for chronic pain. I feel as though you should structure your blog post in terms of glial cells and pain rather than them not being noticed enough.
2. In your second paragraph: “Of note,..” Is not necessary. I recommend just beginning the sentence with “Glial cells have been shown…”. It provides a smoother transition.
3. In your third paragraph, you state that glial cells are activated in patients with chronic pain. Then your fourth paragraph discusses how glial cells are targets for drugs to help chronic pain. I think those two paragraphs should be merged together. For example, talk about how glial cells are activated for chronic pain patients, then talk about how this has caused them to be a new interest for drug targeting. I don’t think the process of how they found glial activation is necessary.
Overall great topic! I hope these suggestions help, happy editing 🙂
-Mehreen Butt
Hi Mehreen,
I edited the structure of my blog post to focus more on glia and pain as opposed to them being overlooked, I removed the sentence including “Of note” completely to better focus my introduction on one point rather than two, and I edited the two body paragraphs such that I would not have to merge them (their individual ideas are more distinct now). Thank you for your suggestions – they were very helpful!
Thanks,
Aakanx
Hey Aakanx,
Interesting post, you had some good figures and explained scientific concepts cleanly. Some points to keep in mind:
-In your second paragraph you talk about the Neuron Doctrine but dont say what this is. As others have said, it feels like your trying to make the post about how Glial cells were not thought to be important and now we know better however, this point is not strong enough. I actually had intensive comments about this issue but decided to just tell you it doesn’t really fit nicely anywhere – i would take it all out.
– your use of colons in the third paragraph could easily be replaced with a period. In the same sentence you could probably take out “integrated imaging technique” its a vague term that adds nothing but length to your post.
– What do you mean by “regional comparisons” in your Figure one caption? You have a good figure but your caption should make it be able to stand alone clearly even out of context.
Keep it up!
Felipe R.M.
Hi Felipe,
I really appreciate your comments – I have made edits accordingly. Firstly, I have better structured my post to emphasize one point instead of two. I removed “neuron doctrine” and “integrated imaging technique.” And I rephrased my Figure 1 caption such that it better stands alone without much context; “regional comparisons” referred to comparisons within/between subject brain regions.
Thanks,
Aakanx
Hi Aakanx,
What an interesting post – I didn’t know that glia cells had roles beyond just neuronal support. You did a great job conveying glia function in terms of pain reception and I liked how you incorporated a study to support the role of nociception. Also, great use of sources. Here are a few suggestions:
– I think the second second sentence of your intro paragraph could be reworded as follows: “Glial cells have surprisingly only recently come to the forefront, despite that fact that they comprise 90% of cells in the brain.”
– On a similar note, I wonder if this statement is entirely true. You introductory paragraph (and your next paragraph) emphasize that glial cells have only recently come to the forefront and only contribute to supporting roles, but then you state that it has been known for over a decade that glia are involved in nociception. That is quite a long time.
– In the intro paragraph, I don’t think ‘thereafter’ is the right term. Perhaps use ‘thus’ or ‘therefore’ as the consequence of glia role is nociception is looking at them as drug targets.
– Just a stylistic thing: figure captions should be left centered OR you should center your figures and caption on the page.
Hope these suggestions help.
Cheers,
Sara
Hi Sara,
Thank you so much for your suggestions! I ended up omitting the sentence with “90 % of cells in the brain,” but I do prefer your phrasing if I had kept the sentence. As I edited the structure of my post to focus less on glial cells “recently coming to the forefront,” I have accounted for your second comment. I changed “thereafter” to “therefore.” I believe I have centred my figures and captions both on the page, as per your stylistic suggestion.
Thanks,
Aakanx
Hi Aakanx!
I found this to be an interesting topic for a blog post – I agree that it is very interesting that what we are talking about in drug discovery and neuro are intersecting. Like Dominique said, I agree that it would make sense to combine your first and second paragraphs, because they appear to overlap a bit. Another suggestion would be to change the introduction to the third paragraph, as I find it a little bit confusing, by first mentioning that this is something that we have know for a while, and then restating it as though it is new research. Perhaps you could combine these two sentences into one? One more specific suggestion would be to further explain the images that you used, and how they relate to what you are saying in the body of your post. Overall, I found the basis of your post really interesting, although it left me with a few more questions, and if the word count allows, I would suggest expanding more on the specifics of some of these studies.
Happy editing,
Mary Anne
Hi Mary Anne,
I agreed with all of your suggestions and have made edits accordingly. I did have some more space in word count and so I was able to expand more on details.
Thanks,
Aakanx
Hi Aakanx,
I really enjoyed reading your blog post and I had no idea how much of a role glial cells have in our bodies! The topic was very related to our Neuroscience unit and it was nice to hear about some of the less discussed cells that are still very important. Your figures were very useful and your captions were descriptive and concise, nice! The second paragraph felt kind of like another introduction to the topic, maybe find a way to combine the first two paragraphs? You also say that glial cells have only come into the light recently but then go on to say that we have known specific things about them for over a decade. This is contradictory and it might be good to specify how “recently” glial cells have really come to the forefront.
Altogether it was a very good read!
Isla
Hi Isla,
Thank you for your comments! I agree with your suggestions; I have made the appropriate changes.
Thanks,
Aakanx