Tag Archives: C1q

Action-packed YouTube video clip

Immune cell in the brain swallows synapses to sculpt neurons during development.

Posted by NIHNINDS (National Institute of Neurological Disorders and Stroke) at YouTube on May 22, 2012.


The green thing is a mouse’s microglial cell. The movie is “courtesy Dorothy Schafer, Ph.D. and Beth Stevens, Ph.D. at Boston Children’s Hospital.” At this blog I have speculated that the kind of process shown in this brief video clip possibly happens less often in the brains of some people because they have lower levels of some of the complement chemicals that are a part of the immune system, with the result being the development of, or the retaining of, childhood or developmental synaesthesia. Some of the complement chemicals mark out synapses for destruction, I believe.

There’s a back-story to my theory

I can show data dating back to the year 2000 that supports my theory that low levels of complement proteins, which are a part of the human immune system, specifically C3, C4 and most likely C1q, are the biological cause of the development of inherited synaesthesia (at least in some cases). Before I had thought of the idea of a link between the immune system and synaesthesia I had, at the blog, published a theory that synaesthesia is in some way the neurological opposite of a variety of dementia named Benson’s syndrome (aka PCA, posterior cortical atrophy), based on my observations and reading. I had speculated that there could be some “magical chemical” that regulated the brain in some way and that oppositely extreme levels of this magical chemical could be the biological basis of both synaesthesia and Benson’s syndrome. Back in 2012 I read a small article in New Scientist magazine that blew my mind, because it appeared that it gave me some major clues about what that magical chemical could be. The article was about the exciting work of Dr Beth Stevens on microglial pruning in the brain and the immune system’s complement proteins. The term “pruning” was familiar to me from all of my reading about synaesthesia, which is a fun heritable brain-based phenomenon which I share with some of my first-degree relatives, along with specific gifts in literacy skills. The term “complement” in the context of the immune system, and the individual names of complement proteins were also familiar to me.

Being a super-recognizer, I’m pretty good at recognizing patterns, and I recognized that all these elements of information fitted together into an important and original multi-faceted theory. I was so excited that I published a brief outline of my theory at this blog in 2012. In 2013 I was shocked to discover that a prominent synaesthesia researcher and her co-author had published a theoretical journal paper titled “The immune hypothesis of synesthesia” which even included speculation that the “complement system” could be the element of the immune system responsible for the development of synaesthesia. I found no credit given in that paper to me or my blog. As I had published my theory first I believe I should have been fully acknowledged. I never thought that this could have been a case of two separate parties thinking of the same idea independently. I read their paper through and I looked into the educational and research background of both authors and their previous publications and found no study or writing about the immune system and no indication or explanation of why they might have suddenly had their own insight linking synaesthesia with some of the many elements of the incredibly complex immune system that only an immunologist would find interesting. 

This Easter I’d like to pose the question; can Simner and Carmichael offer data dating back to the year 2000 as the basis of their published version of “the immune hypothesis of synesthesia”? I can, and I would be willing to share my data with serious medical researchers.

A while ago I was sorting through some piles of old papers that I had stowed away years ago without sorting through them. These things happen during a busy family life. These piles had been sitting around for years, some of it photocopies of articles from New Scientist magazine that had struck me as interesting but which I hadn’t always had the time to read through properly. I was amused to find that I had stowed away an article from the March 1st 2008 issue titled “Thought control” by Bijal Trivedi. It was all about exciting research by the likes of Carla Shatz, Ben Barres, Simon John, Staffan Cullheim, Eliezer Masliah, Robert Terry and Lisa Boulanger about synapse loss in dementia and the interesting things that elements of the immune system appeared to be doing in the brain, contrary to the received wisdom that there is a thing called the blood-brain barrier that keeps the immune system out of the brain. I’m not sure whether or not I had read the article back then, but I can understand why it had sparked my interest. Back then it wasn’t enough of a spark to give me the idea of a link between the immune system and synaesthesia, because back then I hadn’t even heard of the terms “super-recognizer” or “Benson’s syndrome”, in fact the concept and the term of “super-recognizer” hadn’t yet been published. Back then I had not the slightest inkling that I had better than average ability in face recognition, so I hadn’t started thinking about whether it was more than a coincidence that I was both a synaesthete and a super, and which parts of the brain might be atypical in both. I hadn’t read the human interest story in The West about a Perth citizen who had been diagnosed with Benson’s, and felt curious about how the description of that type of dementia sounded like the opposite of skills that were superior or associated with synaesthesia in myself and kin. I must have forgotten about the content of the 2008 New Scientist article, if I had ever read it at all, because it would have been the ribbon which I could have used to wrap up my package of ideas neatly. Curiosity can be rewarded, even if it takes a couple of coins before the penny drops.


Is synaesthesia caused by low levels of complement? Is Benson’s syndrome (PCA) caused by too much complement C3? Could synesthesia and posterior cortical atrophy be considered in some way opposites?

A note of warning – If you are thinking about copying or plagiarizing any of the text, ideas or descriptions in this post and using it as your own work without giving me (C. Wright, author of the blog “Am I a Super-recognizer?”) the proper acknowledgement and citations, then think again. If you do that you will be found out and you will regret it. If you want to make reference to this post or any of the ideas in it make sure that you state in your work exactly where you first read about these ideas. If you wish to quote any text from this post be sure to cite this post at this blog properly. There are many established citation methods. If you quote or make reference to material in this blog in your work, it would be a common courtesy to let me know about your work (I’m interested!) in a comment on any of the posts in this blog. Thank you.

Top of C3 theory post

A quote from New Scientist magazine about a study of microglia responding to changes in synaptic function in mice by Assistant Professor Beth Stevens and colleagues:

“Synapses were marked out for destruction through labelling with an immune chemical called C3”

Immune cells gobble up healthy but idle brain cells. 1 June 2012 by Andy Coghlan New Scientst. Magazine issue 2867. http://www.newscientist.com/article/mg21428675.500-immune-cells-gobble-up-healthy-but-idle-brain-cells.html

A quote about her research at Prof Stevens’ professional web page:

“C1q and downstream complement proteins target synapses and are required for synapse elimination in the developing visual system.”

Beth Stevens, PhD, Boston Children’s Hospital http://www.childrenshospital.org/cfapps/research/data_admin/Site2674/mainpageS2674P0.html

A quote from Wikipedia about synaesthesia:

“This cross-activation may arise due to a failure of the normal developmental process of pruning, which is one of the key mechanisms of synaptic plasticity, in which connections between brain regions are partially eliminated with development.”

Wikipedia contributors Neural basis of synesthesia.  Wikipedia, The Free Encyclopedia, 25 May 2012, 01:45 UTC, http://en.wikipedia.org/w/index.php?title=Neural_basis_of_synesthesia&oldid=494244732

A quote from Wikipedia about Benson’s syndrome or Posterior Cortical Atrophy:

“The disease causes atrophy of the back (posterior) part of the cerebral cortex, resulting in the progressive disruption of complex visual processing.

Wikipedia contributors Posterior cortical atrophy Wikipedia, The Free Encyclopedia, 4 February 2012, 22:34 UTC, http://en.wikipedia.org/w/index.php?title=Posterior_cortical_atrophy&oldid=475033670

Two quotes by me from this blog:

“The idea that I have something like the opposite of Benson’s syndrome would neatly draw together all the elements of some odd phenomena that I have observed over a number of years…”

“I guess the million-dollar question is  – why does Benson’s syndrome affect only some specific parts of the brain? What is it about a certain group of areas of the brain that appear to make these areas prone to hyperconnectivity in some families, and vulnerable to dysfunction in Benson’s syndrome? Is there some magic chemical or process that regulates growth in these areas of the brain? I doubt that the answer could be so simple.”

The Opposite of Benson’s Syndrome? by C. Wright Am I a Super-recognizer? January 4, 2011. https://superrecognizer.wordpress.com/2011/01/04/the-opposite-of-bensons-syndrome/

My doubt has suddenly evaporated! Could complement be the “magic chemical”? Where’s my Nobel Prize in Physiology or Medicine?

The DOI link in the New Scientist article discussed above doesn’t work, but I’m quite sure this is the journal paper that the article is about:

Dorothy P. Schafer, Emily K. Lehrman, Amanda G. Kautzman, Ryuta Koyama, Alan R. Mardinly, Ryo Yamasaki, Richard M. Ransohoff, Michael E. Greenberg, Ben A. Barres, Beth Stevens Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner. Neuron. Volume 74 Issue 4 691-705, 24 May 2012. 10.1016/j.neuron.2012.03.026 http://www.cell.com/neuron/retrieve/pii/S0896627312003340

A number of other interesting journal papers can be found through Prof. Steven’s web page, some available to read in full text (if you can find the button to click on in the top right corner of the PubMed page). I also found a recently published item by Stevens and colleagues that looks like it is about the same subject as the New Scientist article, published in a conference abstract supplement of the journal Schizophrenia Research, which is a bit of a mystery as I didn’t think the title suggested schizophrenia. You need to pay to read the full text, which I didn’t. http://www.sciencedirect.com/science/article/pii/S0920996412700397

Here’s something else to read, if you’re keen. You can read the whole thing for free:

Marie-Ève Tremblay, Beth Stevens, Amanda Sierra, Hiroaki Wake, Alain Bessis and Axel Nimmerjahn The Role of Microglia in the Healthy Brain. Journal of Neuroscience. 9 November 2011, (45): 16064-16069; doi:10.1523/JNEUROSCI.4158-11.2011  http://www.jneurosci.org/content/31/45/16064.long


C3, C4, C5....

C3, C4, C5….