Category Archives: Autism
Public Release: 21-Jul-2016
Transcript of video content:
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Got 2 minutes to spare? Then sit back and enjoy a mix of fact, fantasy & tongue-n-cheek from “yours truly” (Dr. Anthony G. Payne)
I have worked with a coenzyme called pyrroloquinoline quinone (PQQ) for quite a while now and think it is worth a “look see” by physicians and others for its preventative and therapeutic potential. Let’s dive into this now:
First, let’s “do the time warp, now”: During 1994-5 I worked in an Ag lab and large greenhouse complex outside Lincoln, Nebraska (Which was devoted to the testing of various nature-derived growth accelerants on culinary & medicinal mushrooms). One of the principle consulting researchers who rubbed elbows with me was Andy Anderson, PhD, who discovered a radioresistant bacterium back in 1956 while irradiating food at the Oregon Agricultural Experimental Station in Corvallis (As I recall from our chitchat, he was irradiating canned foods to see if this would reliably preserve them against spoilage). The bacterium was subsequently dubbed Deinococcus radiodurans and is indisputably the most radioresistant organism discovered to-date.
Anyway, while kibitzing with Dr. Anderson we discussed possible mechanisms by which Deinococcus radiodurans was able to escape destruction by intense gamma ray exposure. One of things we tossed about as a putative key player was, yes, pyrroloquinoline quinone (PQQ). There was, in fact, things pointing to this that went back in the literature to the 1960s (PQQ was discovered in 1964, as I recall).
Now, fast forward to modern times: Doctors, patients, consumer advocates and others are mindful that x-rays, SPECT scans, and other screening scans that involve radiation can have deleterious “downstream” effects — which got me to thinking about Dr. Anderson and our chat about pyrroloquinoline quinone (PQQ). Mind you, I’ve shared information on use of purified PQQ with physicians and others as a promising preventative/remediative measure with respect certain cardiovascular and neurologic conditions and insults for many years now (In part due to its ability to stimulate mitochondriogenesis). Granted, it is poorly assimilated in the gut but thankfully works at low levels and is, in fact, recycled many times over in vivo. But I hadn’t thought about PQQ as a possible radioprotective compound since 1994 and my days in “The little lab on the prairie”.
With that old chat-fest with Dr. Anderson in mind I shot over to PubMed and did a search to see if any contemporary studies had been done that linked PQQ to radioprotection. And, bingo, I struck pay dirt —
|Pyrroloquinoline quinone and a quinoprotein kinase support γ-radiation resistance in Deinococcus radiodurans and regulate gene expression.|
|Rajpurohit YS, Desai SS, Misra HS.|
|J Basic Microbiol. 2013 Jun;53(6):518-31. doi: 10.1002/jobm.201100650. Epub 2012 Sep 7.|
|Production and radioprotective effects of pyrroloquinoline quinone. (Mouse study)|
|Xiong XH, Zhao Y, Ge X, Yuan SJ, Wang JH, Zhi JJ, Yang YX, Du BH, Guo WJ, Wang SS, Yang DX, Zhang WC.|
|Int J Mol Sci. 2011;12(12):8913-23. doi: 10.3390/ijms12128913. Epub 2011 Dec 5.|
In light of the animal study especially, it follows that PQQ given well before & following an x-rays, SPECT scans & the like could (should?) afford radioprotection of those neural & other tissues it cycles through.
Now, this isn’t all there is to PQQ. While visiting with a physical anthropologist we got into discussing one of my favorite hominins (australopithecines), Paranthropus boisei (Also referred to as Australopithecus boisei) who is popularly referred to as “Nutcracker Man”. I knew from various recent papers & popular articles that Paranthropus boisei thrived on a tuber known as “tiger nuts”. See this article: http://www.sci-news.com/othersciences/anthropology/science-paranthropus-boisei-tiger-nut-diet-01680.html
Anyway, with PQQ on my mind I asked this anthropologist if she knew whether “tiger nuts” are rich in this coenzyme. She didn’t know so we did a literature search and found that PQQ tends to occur in very high amounts in tubers!
While it will take gas chromatograph testing to determine the exact PQQ content in tiger nuts, I think the fact they helped nourish & sustain such a robust hominin as Paranthropus boisei suggests they may also be worth consuming on the part of physically active folks (Athletes especially) as well as those predisposed to developing certain neurologic or cardiovascular diseases and conditions. I then did some on-line digging and came up with a US based firm that markets tiger nuts and has posted this tuber’s impressive nutritional profile: https://tigernutsusa.com/ ( Note Bene: I have no commercial or other interest in this firm or any other that grows, harvests, sells, markets, or processes PQQ or tiger nuts).
So, all told, I think there is (ahem) “food for thought” in all this with respect to the possible use of PQQ by radiologists, dentists and other health care professionals in patients of theirs doing radiation-based scans (pre & post exposure measure), and also for the inclusion of tiger nuts in various diet plans and programs.
Go to http://www.scribd.com/doc/223658050/PQQ-Nutcracker-Man-Tiger-Nuts-Radiation-protection-heart-nervous-system-benefits where you’ll find 52 citations from PubMed on PPQ. Among these you will find published papers suggesting PQQ might prevent and/or remediate Alzheimer’s disease related processes, neural damage due to methylmercury exposure, TBIs, and much more in patients (Granted, many of these studies involved cell culture work but there are also those involving animal models and a few, humans).
Choctaw Doc (Anthony G. Payne)
REVIEW ARTICLE ON PQQ & HEALTH:
REVIEW ARTICLE ON PQQ IN VARIOUS BIOLOGIC PROCESSES:
HYPOTHESIS: Two ways in which cytomegalovirus carrying male germ cells may play a role in the genesis of autism spectrum disorder
Recently a paper was published showing that 33 of every 10,000 children born to older men (40 years of age or older) have autism spectrum disorder compared to 6 of every 10,000 children born to younger men (<30 years of age). Excerpts from a report in Nature News titled “Male biological clock possibly linked to autism, other disorders” will help flesh this out:
“In a study of more than 100,000 people, along with records about their parents’ ages, Avi Reichenberg at King’s College London and his colleagues found that 33 out of every 10,000 offspring of men 40 years or older had autism spectrum disorder—a 475% increase compared to offspring of men younger than 30, who fathered afflicted children at a rate of 6 per 10,000 (Arch. Gen. Psychiatry 63, 1026–1032; 2006). This association is now being tested in a larger study, says Reichenberg. A study this September showed a similar but less pronounced association of parental age with bipolar disorder (Arch. Gen. Psychiatry 65, 1034–1040; 2008).
“Spontaneous mutations can arise in both sperm and eggs. As women age, for example, they have an increased risk of delivering a child with Down’s syndrome and other disorders caused by large-scale chromosome problems in eggs, such as trisomy. But unlike eggs, sperm arise from stem cells that continuously divide—about 840 times by the time a man is 50 years old (Cytogenet. Genome Res. 111, 213–228; 2005). The theory is that the chances of mutations increase with each round of DNA replication—a process that could underlie estimates that the mutation rate in males is about five times that in females (Nature 416, 624–626; 2002).
“Any mutation you can think of occurs more frequently in the sperm of older men,” says Sebat.
For a very long time it was thought mutations associated with the passage of time was something primarily peculiar to the ovum (A woman’s unfertilized egg). The belief that the genetic material in male sperm was somehow spared age-related mutations was driven home to me by a stem cell biologist I interacted with from 2008 to 2010, who was convinced that the male body had mechanisms in place that help insure that few if any mutations wound up in mature male sperm in healthy males regardless of age. This struck me as wishful thinking and I was quick to lock horns with this chap over this. Now comes tentative evidence – again, the results of the study just announced (above) – that would appear to vindicate my position. Although it is always fun to be right, I got to wondering what other players besides normal aging might be producing mutations in at least some men’s semen that set the stage in their progeny for the development of autism and other neurological conditions. The first thing that popped to mind was pathogenic microorganisms – especially viruses. A quick check of published research brought up one particular bit of research that seemed to signal I was on the right track:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3143078/pdf/2042-4280-2-7.pdf – “Detection of human cytomegalovirus in motile spermatozoa and spermatogenic cells in testis organotypic culture”
The long story short with respect to this study is that it found HCMV in male germ cells from semen samples (91 fertile and 47 infertile men) and in testis tissue culture. There was a decrease in the number of immature germs cells that is believed attributable to the HCMV. In short, the presence of the HCMC in a man’s reproductive tract – and, mind you, 50-80 of every 100 Americans harbor the HCMV according to the CDC – tosses a monkey-wrench in the genetic apparatus of sperm resulting in infertility. There are undoubtedly other viruses that populate the male reproductive system including others of the herpes family that may well have a similar effect.
What if the genetic changes go beyond infertility? What if HCMV produces genetic mutations in fertile men’s sperm? Some of these, I conjecture, could set the stage for producing autism in children they father.
Now – and here is where my off-the-cuff theorizing gets really interesting – what would happen if a HCMV-infected spermatozoon fertilizes a female ovum? In some instances it becomes activated and effects varying damage to one or more developing fetal tissues/organs including the brain and even generates defects severe enough to result in miscarriage. However, what I propose is that most HCMV transmitted to a fetus at conception by an infected male germ cell (sperm) is latent (inactive)and winds up in various tissues though primarily the CNS [The virus preferentially infects neurons probably brain stem & progenitor cells too (This is the case in mouse models of CMV infection)]. Though not active in the sense it produces clinical symptoms it could conceivably cause subtle neurologic changes and damage that is later manifest as autism spectrum disorder (One murine study notes: “Infection of neurons may tend to become persistent by evasion of immune reactions, anti-apoptotic effects and neuron-specific activation of the e1-promoter, presumably causing functional neuronal disorders. It has also been shown that CMV infection in developing brains may become latent in neural immature cells”. These effects were observed in active infections. However, it may affect subtle genetic damage in neurons in a child’s developing brain though the virus is latent or largely inactive).
This body of conjecture is testable. And, if it turns out HCMV is damaging some men’s germ cell DNA in ways that set the stage for autism (and possibly other neurologic disorders) in children they father and/or the virus is being passed on to zygote (by the male gamete) and ultimately the embryo’s developing CNS where it sets the stage for the development of autism or other neurologic disorders years after birth, testing for the HCMV’s presence in semen and (when determined to be present) interfering with the HCMV in the man’s reproductive tissues by treating with extant antiviral drugs are measures that might reduce the likelihood the virus will wreck biologic havoc either in the developing embryo or later in the developing baby or child.
I hope some enterprising grad student or researcher transforms my ruminations into suitable bench experiments and runs with it.
Additional Reading: This paper titled “Neuropathogenesis of Congenital Cytomegalovirus Infection: Disease Mechanisms and Prospects for Intervention” delves deeply into technical issues I only touched on above as well as prevention and treatment aspects of HCMV infections.
© 2012 by Dr. Anthony G. Payne. All rights reserved. If you are a grad student or researcher who runs with one or both of the ideas articulated above, please let me know what you do and the outcome: firstname.lastname@example.org
You can access this hypothesis as a PDF document by clicking this link: http://www.healingcare4u.org/articles/HYPOTHESIS%20-%20HCMV%20and%20autism%20-%209-9-2012.pdf