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1. 10/9/2014 An Unexpected Discovery in the Brains of Autistic Children | LinkedIn High Sch Study in Canada - You pay over $10K for your child's annual tuition? Try…
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  • 1. 10/9/2014 An Unexpected Discovery in the Brains of Autistic Children | LinkedIn High Sch Study in Canada - You pay over $10K for your child's annual tuition? Try High Sch in Canada. Society for Neuroscience 30,078 members Member Discussions Promotions Members Search An Unexpected Discovery in the Brains of Autistic Children Gerald Nsugbe -- Top Contributor We may be permitted to adopt a useful but temporary working model, the 4 Cs (cause, consequence, compensation and confound), as described in a previous article (http://sfari.org/news-and-opinion/viewpoint/2012/insights-for-autism-from-schizophrenia):- 1. We postulate the cause of autism to be disturbed foetal circulation within one or more layers of the cerebral cortex under development in a particular region especially during the second and third trimesters of pregnancy; 2. Under compensation, we postulate that other layers of the cortex having a separate but undisturbed supply of blood would, as a result, receive more nutrients than would normally be the case and thus compensate for the lack of development of adjacent layers affected by circulatory disturbance. 3. Under the heading of consequence, therefore, normally nourished cortical layers would erupt into those poorly nourished cortical layers: http://www.wired.com/2014/03/disordered-cortex-autism/ . 4. Under the hypothetical heading of ‘compound’, we have the disordered arrangement of cortical layers (eruption) resulting in the symptoms of autism characterized by social, ehavioural and intellectual deviance or abnormality. In the most serious cases of autism, all layers of the cortex of a particular region may conceivably be affected by stunted development as a result of particularly poor supply of nutrients to all the layers in that region. Circulatory disturbance arising from a heritable and spontaneous over-constriction of a blood vessel-- potentially in any part of the human body—is, in my view, a well-established but very poorly understood phenomenon in medical physiology. It is apparently due to a highly variable pattern of mutant or polymorphic genetic factors associated with the nervous system which I have tried to fathom in my book and characterized as libido-related in evolutionary terms: https://createspace.com/4515056, Amazon.com or http://www.amazon.com/dp/B00I1LSBHO. In cases where precocious development of a certain mental faculty is observed in autism, we may postulate the reverse of circulatory disturbance to have occurred, resulting from over-supply of blood nutrients to a particular region of the developing cortical layers occasioned by over-activity of parasympathetic impulses of the autonomic nervous system and the excessive dilatation of blood vessels. Viewed thus, there are potentially fewer inherent contradictions in the explanation of autistic disorders.A n Unexpected Discovery in the Brains of Autistic Children | WIRED wired.com Nobody knows what causes autism, a condition that varies so widely in severity that some people on the spectrum achieve enviable fame and success while others require lifelong assistance due to severe problems with communication, cognition, and... Like (3) 0Comment (14) 0Unfollow 05 days ago Comments Dr Pavithra Krishnan, Aleksandra Richardson and 1 other like this 14 comments 0Jump to most recent comment Top Contributors in this Group Gerald Nsugbe -- Your group contribution level Congrats! Regularly add great discussions and comments to stay a Top Contributor. Latest Activity  See all members - Top Contributor Matthew Worley likes a discussion in Society for Neuroscience. Sven H. Do postdocs need leadership skills? Is it really necessary to invest time and money to train postdocs in management and leadership skills? Do postdocs need leadership skills? In the US postdocs are often “ lab rats” who primarily create experimental data. In Europe, they have more management functions. They are in a sandwich position between the crazy professor and the demanding PhD... 57m ago Adolfo Talpalar commented on a discussion in Society for Neuroscience. SAMUEL BERNARDO T. ¿BEBER VINO PROMUEVE LA LONGEVIDAD? Research on resveratrol may someday lead to improved health and extended life. However, it appears that there is no Gloria Hoffman Professor at Morgan State University While vascular alterations could be an important contributor in autism, I believe it is overly https://www.linkedin.com/groupItem?view=gid=131689type=memberitem=5924176822693568512commentID=5925505721234919424rep… 1/6
  • 2. 10/9/2014 An Unexpected Discovery in the Brains of Autistic Children | LinkedIn Gloria Home Profile Connections Jobs Interests Business œ Search groups... Services
  • 3. Upgrade Tamara Manjeet link between dietary resveratrol levels and the rates of heart disease, cancer, and... more Can drinking wine really promote longevity? Research on resveratrol may someday lead to improved health and extended life. However, it appears that there is no link between dietary resveratrol levels and the rates of heart disease, cancer, and death in humans.... 1h ago Manjeet Sharma likes a discussion in Society for Neuroscience. Namita R. Study Identifies Unexpected Clue to Peripheral #Neuropathies - Neurological Associates of West Los Angeles http://ow.ly/CpfAg New research shows that disrupting the molecular function of a tumor suppressor causes improper formation of a protective insulating sheath on peripheral nerves – leading to peripheral neuropathies... more Study Identifies Unexpected Clue to Peripheral Neuropathies -... New research shows that disrupting the molecular function of a tumor suppressor causes improper formation of a protective insulating sheath on peripheral nerves – leading to peripheral neuropathies and muscle wasting in mice similar... 2h ago See all activity- About Feedback Privacy Terms LinkedIn Corp. © 2014 simplistic to assign it as the CAUSE. Data from autistic individuals who had the disorder as a consequence of thalidomide treatment have autisic phenotypes because select neurons of the brainstem failed to form, The largest genetic component in autism arises from failure of neurons to produce FMRP and that too is not directly ascribable to a vascular source. Paths to autism like other functional disorders are very likely diverse. Like (1) 0Reply privately0Flag as inappropriate 04 days ago Manjeet S. likes this Tamara Cutler Student at University of California, Los Angeles I agree with Gloria. Any model proposing a single cause is inadequate. A good model will accommodate many causes converging on the phenotypic outcome. Maternal antibodies that bind to neuron specific proteins (http://www.medscape.com/viewarticle/807760) and several environmental toxins (http://www.sciencedaily.com/releases/2012/04/120425140118.htm) that interfere with neuronal development are already suspected. Like (1) 0Reply privately0Flag as inappropriate 03 days ago Manjeet S. likes this Feedback Manjeet Sharma Researcher Dr Hoffman, In reproductive biology, the hpg mouse model of infertility occurs naturally and is due to the failure of some neurons to move in their designated region from the neural crest to the hypothalamic region during development. Therefore, their hypothalamo-pituitary axis remains defective because gonadotrophin releasing hormone is not available to the pituitary . Reproductive hormones are not released. Exogenous hormones reverse the infertility. There is a total disconnect between the hypothalamus and pituitary. This neurodevelopmental disorders has been documented (and is due most likely due to an aberration of a factor involved in neuronal migration. Here, in the case of autistic individuals, a similar event seems to be happening in the cortical regions associated with socialising/intellectual (deviant) behaviours. When a child is born it has already developed through 9 months (almost three quarters of a year!). Its biological age is already 9 months at birth. Why do we attach more importance to his administrative age rather than his biological age? Exposure to exogenous chemicals during 3 quarters of a year (in utero) must therefore be taken into account (rather than post natal exposure) when considering developmental defects since structural changes (and neuronal migration) are less likely to occur after birth. Nutrition in utero could also be very important given the spectrum that exists in this disorder. Like 0Reply privately0Flag as inappropriate 03 days ago Gerald Nsugbe -- Top Contributor Gloria, I am happy that the word “functional” appears in your polite riposte to my comment because I am only concerned with natural causes of autism which thalidomide treatment is clearly not. In the field of medicine, although not myself a medic, I have observed that distinct sub-types within a particular disease spectrum, such as ASD and IBS (Irritable Bowel Syndrome), invariably mimic themselves under different polymorphic and mutant guises, for example CGG repeats in the case of X-Fragile Syndrome: www.casinapioiv.va/content/dam/accademia/pdf/sv117/sv117- bear.pdf. Deletion or silencing of the FMRP gene, which leads to excessive synaptic plasticity, simply mimics the related emotional disorder of schizophrenia with positive symptoms in which there is analogous neuronal hyper-excitability, for instance in relation to visual cortex neurons. I have explained this hyper-excitability to be related to the parasympathetic arm of the autonomic nervous system; while, the negative symptoms of schizophrenia (which shares with ASD the symptom of social withdrawal) I have described to be related to an over-excitability of its ‘sympathetic’ counterpart (https://createspace.com/4515056, Amazon.com; or, http://www.amazon.com/dp/B00I1LSBHO). Suggested It is precisely discussion this same over-activity of the sympathetic arm which clearly gives rise I have to over-done constriction this before of when blood vessels postulated to be a cause of at least a proportion of cases the of group ASD, no was matter getting how st... small. What ) is important to note here is that the main cause of ASD (excessive synaptic excitability resulting from absence of FMRP) mimics/parallels neural over-excitability associated with circulatory disturbance regarding a putative and far less significant proportion of cases of autism. Tamara, in line with the particular point you raised, do you not think it possible, even probable, that the fetal circulatory disturbance I have postulated could give rise to an autoimmune response on the part of the fetus which may in turn trigger maternal antibodies especially in a situation where there is Rhesus factor incompatibility between the mother and fetus? Moreover, circulatory disturbance in the manner I have postulated could easily lead to a pathological environmental insult associated with cortical layer development or under-development. Manjeet, thank you for your contribution and, in particular, for acknowledging nutrition as possibly being a very important factor. The issue of neurons failure to move ‘in their designated region from the neural crest to the hypothalamic region during development’ is also connected with some genetic aberration, This is true of Kallmann Syndrome (KS) which I also mention in my book as being a possible phenotypic result of genetic damage or deletion due to the adverse effects of overactive autonomic nervous system impulses causing over-constriction of blood vessels supplying the affected part of the developing fetal brain. https://www.linkedin.com/groupItem?view=gid=131689type=memberitem=5924176822693568512commentID=5925505721234919424rep… 2/6
  • 4. 10/9/2014 An Unexpected Discovery in the Brains of Autistic Children | LinkedIn Gloria Gloria Gloria Tom Delete 03 days ago Gloria Hoffman Professor at Morgan State University Manjeet, I am a little uncertain whether the hpg mouse you mentioned was the one used years ago to understand the GnRH system, but in that mouse, the neurons went to the correct place but lacked the ability to synthesize GnRH. That said, on the Autism end of the world, the studies I was referring to were published years ago by Patty Rodier at Rochester. She is an expert in developmental sequences and based on the associated developmental abnormalities in the autistic thalidomide cohort in Germany could pinpoint the exact day the mother received the drug and which neurons were leaving the mitotic cycle that day. That study then showed the facial motoneurons failed to develop and then produced the lack of affect that accompanied the behavioral syndrome. While we are still trying to understand the Fragile X disorders (and this is not going to be a simple one-system model, it is going to be important to understand the old adage that many roads lead to Rome. I think it is interesting that the vasculature could be affected as a consequence of disruptions in many different components of neural function. Indeed another interesting disorder was septo-optic dysplasia in which the pituitary fails to be in the right location (since there is no optic chiasm to stand behind, and in that instance, the pituitary portal vasculature is missing and ergo! no pituitary function. Do we really fully understand why vessels locate where they do in the brain? - fixing it will be the challenge. Like 0Reply privately0Flag as inappropriate 03 days ago Gloria Hoffman Professor at Morgan State University I'm sure anyone who has led gross anatomy laboratories or done angiograms can point out variations is vessel patterns that could have functional consequences. Like 0Reply privately0Flag as inappropriate 03 days ago Gloria Hoffman Professor at Morgan State University The point I was trying to make with the thalidomide example is that one can get a syndrome from a variety of mechanisms and even though that drug was easy to cast in that role, one could certainly affect neuron patterning by any of many steps. The autoimmune idea has only one slight hitch - the fetal immune system is largely incompetent in utero and maternal antibodies are what protect the fetus early on. Perhaps some disorder then arises as the newborn's immune system kicks in, but we must keep an open mind that it could be a subgroup in the autism spectrum that would be affected by that mechanism not likely all those affected. I recall reading some articles out of the Brain Institute in California who also associated immune function with autism but but we must keep in mind that correlation is not causality. Like 0Reply privately0Flag as inappropriate 03 days ago Tom Lord Owner, Unbounded River LLC There are many things that can be said about the brain. All are partly true but none are completely true. I'm sure blood flow and nutrition are important but I believe that the most promising research is on a different track. 200 years ago the rate of autism was about 1 in 10,000. The rate jumped up dramatically in the 1950s to where it is now at a rate some say is as high as 1 in 75 children. Most children with autism are boys. What happened in the 1950s and beyond that could have led to this dramatic increase in autism spectrum? In the 1950s farmers began to use huge amounts of chemical pesticides. Hundreds of millions of tons of these pesticides are dumped into the food supply every year. Even pesticides that are banned in the United States are still used in countries that the US imports food from. There can be many causes of autism. But the impact of hundreds of millions of tons of pesticides dumped into the food supply every year should not be overlooked. But there are huge industrial and political forces that do not want this information to be disseminated. John Boehher, the US speaker of the House is from Iowa and he is bought and sold by the corn industry. Genetic engineering of basic foods such as corn as wheat are allowed without any government regulation. Genetically engineered wheat now has a higher glycemic index than table sugar. Corn is being grown that can produce its own 'natural pesticide' to fight off hostile insects. When a child is in the womb it has more neurons than an adult. In the third trimester, the stem cells differentiate and become specialized cells. There is also a process called 'pruning' where unused neurons die off. The brains of Autistic children have more neurons than the brains of normally developing children. It would seem that a genetic change takes place that interferes with this complex process of pruning and differentiation. The genetic change is most likely on the Y chromosome that determines the sex of the child and that is why more children with autism are boys. There is no simple fix for this problem. I do believe that if commercial pesticides were removed from the food supply, the rate of autism would plummet. However, these genetic changes are cumulative and they are passed down from generation to generation once the change takes place. These are all complicated processes. Is a genetic fix possible? I wouldn't rule it out however we would still have to remove the poisons from the food supply. Currently there is no political action to do this since big money has purchased our elected representatives to work against needed change. Like (2) 0Reply privately0Flag as inappropriate 03 days ago Howard E., Tamara C. like this https://www.linkedin.com/groupItem?view=gid=131689type=memberitem=5924176822693568512commentID=5925505721234919424rep… 3/6
  • 5. 10/9/2014 An Unexpected Discovery in the Brains of Autistic Children | LinkedIn Manjeet Tom Manjeet Sharma Researcher Dr Hoffman, it is the same natural mutants hpg mice. Initially it was said that there was a problem with migration of neurons but later on it was clarified that the problem is with the GnRH synthesis (defective version is still being synthesized but it lacks the LHRH activity). Thalidomide horror would be difficult to forget. I did read that it also affected the vasculature which means a lot for the fetal development while in utero.In fact, some time back I came across a report which suggested that the same thalidomide could be useful to stall HIV proliferation/integration? Is it right. If it is, then the drug has the potential to interfere with fetal gene expression which could be responsible for some of the structural changes seen in autistic brains. I was working with Tamoxifen some years back. The drug affected the viability of the pups sired by treated males. When we looked at the histology, we found that the vasculature was severely affected in the resorbed fetuses and the development was stalled at about 9-11 days of age. In fact, the student who was looking into this effect did immunohistochemistry of the resorbed fetuses vs age matched control fetuses and suggested that VEGF appeared reduced. Drugs can also have a direct effect on the development of blood vessels with consequences to fetal development. Like 0Reply privately0Flag as inappropriate 02 days ago Gerald Nsugbe -- Top Contributor The point which I failed to emphasize in my comment in which I mentioned Kallmann Syndrome is an analogous situation: in which a proportion (at least 50% ?) of cases of Fragile X Syndrome would, in my opinion, involve phenotypic deletion or damage to the FMR 1 gene occasioned by an environmental insult arising from postulated circulatory disturbance. My strenuous argument, therefore, is that there are frequently two basic elements involved in autistic spectrum disorder: a genetically determined predisposition to develop autism and the environment such that any environmental insult may have adverse effects that turns that pre-disposition into full-blown autism as in my putative cases of Fragile X Syndrome. I put it to Tom Lord, therefore, that all that has happened in the past fifty or so years is that toxic elements in the food chain partly arising, as you say, from the importation of foods grown with banned pestic
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