Ginger Taylor Questions Seth Mnookin
Autism Research Institute Features Network for Individuals with Hearing and Visual Impairments

AofA Science Summary: possible link between the elevated serum levels of neurokinin A and anti-ribosomal P protein antibodies in children with autism

Science post imageJ Neuroinflammation. 2011 Dec 21;8(1):180. [Epub ahead of print]

The possible link between the elevated serum levels of neurokinin A and anti-ribosomal P protein antibodies in children with autism.

Mostafa GAAl-Ayadhi LY.




Neurogenic inflammation is orchestrated by a large number of neuropeptides. Tachykinins (substance P, neurokinin A and neurokinin B) are pro-inflammatory neuropeptides that may play an important role in some autoimmune neuroinflammatory diseases. Autoimmunity may have a role in the pathogenesis of autism in some patients. We are the first to measure serum neurokinin A levels in autistic children. The relationship between serum levels of neurokinin A and anti-ribosomal P protein antibodies was also studied.


Serum neurokinin A and anti-ribosomal P protein antibodies were measured in 70 autistic children in comparison to 48 healthy-matched children.


Autistic children had significantly higher serum neurokinin A levels than healthy controls (P < 0.001). Children with severe autism had significantly higher serum neurokinin A levels than patients with mild to moderate autism (P < 0.001). Increased serum levels of neurokinin A and anti-ribosomal P protein antibodies were found in 57.1% and 44.3%, respectively of autistic children. There was significant positive correlations between serum levels of neurokinin A and anti-ribosomal P protein antibodies (P = 0.004).


Serum neurokinin A levels were elevated in some autistic children and they were significantly correlated to the severity of autism and to serum levels of anti-ribosomal P protein antibodies. However, this is an initial report that warrants further research to determine the pathogenic role of neurokinin A and its possible link to autoimmunity in autism. The therapeutic role of tachykinin receptor antagonists, a potential new class of anti-inflammatory medications, should also be studied in autism.



More on PBDE's

Polybrominated diphenyl ethers in relation to autism and developmental delay: a case-control study

"Few studies of autism have addressed environmental pollutants, and little research has been conducted in humans to assess neurodevelopmental toxicity of brominated flame retardants. Polybrominated diphenyl ethers (PBDEs) are flame retardants used widely in carpeting, foam furniture and car seats, textiles, plastic casings for television sets and computers, household appliances, and construction materials. The foam products have contained primarily penta-BDEs; plastic casings on small appliances and computers have been primarily octa-BDEs; and television sets, electrical wiring, and backings on draperies have generally been deca-BDEs [1]. Levels of PBDEs in human breast milk rose rapidly for several decades in Sweden but then declined, most probably in response to regulatory actions [2]. Concentrations reported in human blood are consistently higher in the U.S. than in Europe [3,4] and recent reports suggest that body burdens in California are among the highest worldwide [5-7]. Food, dust and air are the main routes of exposure [4,8].PBDEs cross the placenta and are mobilized into breast milk during lactation [9,10]. A body of evidence has accumulated from experimental animal studies showing adverse neurodevelopmental consequences following prenatal and early life exposures [11-14]. These include hyperactivity and permanent alterations in spontaneous behaviors, deficits in learning and memory, and failure to habituate to novel stimuli, with effects seen at exposure levels comparable to those observed in humans [14]. In mice, exposures on postnatal days 3 and 10, but not postnatal day 19 altered motor behaviors, suggesting specific windows of vulnerability that translate to prenatal periods in humans [12].Possible mechanisms relevant to neurodevelopmental toxicity include disruption of thyroid hormone or sex steroid homeostasis during the prenatal period [15-18], a period in which these systems play critical roles in fetal development, particularly in the formation of the external granule cell layer of the cerebellum [18]. PBDEs also show evidence of immunotoxic effects in rodent experiments [19]. Meanwhile, increasing research suggests neuroimmune pathways could contribute to autism [20,21]. In mechanistic studies, PBDEs also disregulate neuronal Ca2+ signaling events [22,23], effects that appear to be magnified by hydroxylation of parent structure and that predict neurotoxic potential [22,24]. Several genes associated with autism risk are tightly regulated by Ca2+ (e.g., neuroligin-3 [25]), or are themselves regulators of cellular Ca2+ signals (e.g., Timothy Syndrome). Several congeners activate the pregnane X receptor, resulting in induction of cytochrome P450 enzymes [26]."

Mouse cerebellar astrocytes protect cerebellar granule neurons against toxicity of the polybrominated diphenyl ether (PBDE) mixture DE-71.

"Astrocytes were found to protect neurons against the toxicity of the PBDE mixture DE-71. Astrocytes from Gclm (-/-) mice, which lack the modifier subunit of glutamate cysteine ligase and, as a consequence, have very low GSH levels, were much less effective at protecting CGNs from DE-71 toxicity. The protective effects were mostly due to the ability of Gclm (+/+) astrocytes to increase GSH levels in neurons. By increasing GSH, GSH ethylester provided a similar protective effect. In vivo, where both neurons and astrocytes would be either Gclm (+/+) or Gclm (-/-), the toxicity of DE-71 to CGNs is predicted to vary 16.8-fold, depending on genotype. Hence, in addition to being intrinsically more susceptible to DE-71 toxicity because of their low GSH content, CGNs in Gclm (-/-) mice would also lack the full protective effect provided by astrocytes. Since several polymorphisms, including some in the Gclm gene, cause very low levels of GSH, it may be speculated that such individuals might display a higher susceptibility to the neurotoxic effects of PBDEs."

Polymorphisms - low GSH...ok, but other things deplete GSH


The mitochondrial issues may be related to methylation as well as the other metabolic isues related to Ros we have encountered and noted. I don't know if the the specific problems in the release below may be involved in communication/hearing in Autism, but it seems plausiblein many cases.

How Mitochondrial DNA Defects Cause Inherited Deafness

"The team found that cell lines containing this mutation are prone to cell death not directly due to the mutation, but rather because it enhanced a normal chemical modification of the RNA called methylation, which regulates ribosome assembly"...

"Our lab had previously discovered that overexpression of the enzyme responsible for this methylation could cause cell death, even in cells without the deafness mutation,"...

This new mouse model will be instrumental in understanding genetic and environmental factors known to impact mitochondrial disease pathology."

The researchers found that reactive oxygen molecules produced by diseased mitochondria are what trigger events leading to a cell death-inducing gene expression program. By genetically depleting the protein ultimately responsible for activating this programmed cell death response, they were able to restore normal hearing to the mice.

The study not only sheds light on inherited deafness in humans, but possibly also age-related hearing loss and other human diseases. First author Nuno Raimundo, a postdoctoral associate in pathology, said, "Mitochondrial diseases are complicated because different tissues are affected in often unpredictable ways. Defining the molecular mechanism underlying death of only a specific subset of cells in the inner ear is a major step toward unraveling this complexity."


I meant to highlight this quote from the first article which seems a bit at odds with the drum beat of "the genes and their mutations predominantly cause Schizophrenia or Autism". I still believe certain genetic profiles{normally non defective} in the mother and child {and possibly the father to some degree} are more sensitive to insults that lead to Autism.

"Over the past few years, researchers have increasingly recognized that cellular-level changes not tied to genetic defects play important roles in causing disease. There is a range of such so-called epigenetic effects that change the way DNA functions without changing a person's DNA code."


There is a vast amount of information that could be looked at to illuminate how all the transciption and immune reaction homeostasis and function is altered in immune related autism and other immune imbalance conditions including Neurokinin and the others mentioned in this thread along with many other immune compliment factors. The emergence of gene regulation/exprsssion, epigentic changes, and histone/dna/chromatin function may be the central bridge between enviromental factors and the actual link base inherited genetic factors that alone would much, much less often cause autism.

In lupus certain classes of drugs bring about the condition including it seems Isoniazid as it can cause the production of anti-histone antibodies. Noting how vaccines induce dna release and free histone those already susceptible to having a degree of antihistone antibodies may be the ones who are sensitized and develop a chronic dgree of of chromatin alteration in an ongoing condition heightened or caused by certain vaccines. The first piece below focuses on Schizophrenia and these isssues, but it is new apparently as to it's importance. I had already thought this was part of the problem and suggest it will be found as involved in Autism as well. The dgree and timing of the onset of the effects may be a part of the difference in Autism compared to Schizophrenia. The second piece is related , but focuses on Diabetes, epigenetices, and dna methylation.

Brain Cell Malfunction in Schizophrenia Identified

"A great deal of epigenetic research has focused on chemical alterations to DNA itself. Histone alterations have been much more difficult to study because such research requires that the histones and DNA remain chemically intact. Many researchers feared that these bonds were disrupted in the brain after death. However, Thomas's group was able to develop a technique for maintaining the histone-DNA interactions. "While many people thought this was lost, we were able to show that indeed these interactions are preserved in post-mortem brain, allowing us to carry out these studies," said Thomas.

Compared to healthy brains, the brain samples from subjects with schizophrenia showed lower levels of acetylation in certain histone portions that would block gene expression. Another critical finding was that in younger subjects with schizophrenia, the problem was much more pronounced."

Scientists Map Susceptibility to Type 2 Diabetes

"DNA methylation is a naturally occurring mechanism used to regulate genes and protect DNA from some types of cleavage. It is one of the regulatory processes that are referred to as epigenetic, in which an alteration in gene expression occurs without a change in the nucleotide sequence of the DNA. Defects in this process cause several types of disease that afflict humans....

This analysis not only revealed, for the first time, a clear-cut epigenetic signature in T2D, telltale methylation signature marks were also shown to appear on the DNA of young individuals who latter developed impaired glucose metabolism, even before the appearance of clinical diabetic manifestations.

These findings shed new light on the mechanism of individual predisposition to T2D and pave the way for the elucidating of similar mechanisms in a long list of common human diseases, including many metabolic, autoimmune and psychiatric disorders.

Given that epigenetic marks are sensitive to a wide range of environmental clues, including diets, chemical exposures, intrauterine environments, and also to therapeutic drugs, these finding may open the way for the development of new prevention and/or intervention epigenetic therapies."


Fetal cell lines MRC-5,RA27/3,WI-38 are used in the MMR
vaccines from GSK and Merck. Could some protein
particles from the fetal cell line (or contamination)turn on the immune system of these autistic children and injury
occured by the antibodies in the disrupted(by heavy metals,
polysorbates,inflammation etc.)blood brain barrier.If antibodies present,then antigens were introduced.Lot of the parents do not know that fetal cell lines were/are used.So
much for informed choice discussion.There appears to be a good possibility that autism is an auto-immune disorder.Or I would say the children immune system become damaged by the
vaccine.Did you ever wonder why big pharma wanted the blanket immunity?for their "safe and effective" vaccines???


These areas have caught my eye and this article gives a lot of good info about Neurokinin and substance P and its relation to certain processes though in rats. I won't highlight anything, but the article is informative and may tie to the other two pages linked below in scope.

Protein Kinase C Is Involved in Neurokinin Receptor Modulation of N- and L-Type Ca2+ Channels in DRG Neurons of the Adult Rat
The connection to dorsal root ganglia neurons may tie to certain aspects of the biological tied to estrogen levels manifested in girls imparticular.

"Autism, Bizarre Estrogen Dominance and Seizures"

"Estrogen Elicits Dorsal Root Ganglion Axon Sprouting via a Renin-Angiotensin System"


Similar findings in Neuropsychiatric systemic lupus erythematosus

Autoantibodies involved in neuropsychiatric SLE and antiphospholipid syndrome

The role of measurement of serum autoantibodies in prediction of pediatric neuropsychiatric systemic lupus erythematosus

No wonder then that some ASD children, especially on the more severe end, often respond to treatments that are used first line for managing recognised autoimmune disorders such as Lupus and MS. IVIGs are often used, corticosteroids etc.



what is really interesting is that these researchers found higher levels of ostoepontin, substance P, and gangliosides M1 in autism, and that presence of these substances correlates with how badly the kids were affected, how severe their 'autism' ...

How interesting that exactly the same thing is found in HIV infection, where levels of ostoepontin, substance P, and gangliosides M1 in infected children and adults correlates to the severity of the disease and neurological symptoms.


These authors published two more interesting studies this year, both showing correlations between levels of autoimmune markers and autism severity

Increased serum osteopontin levels in autistic children: relation to the disease severity

Increased serum levels of anti-ganglioside M1 auto-antibodies in autistic children: relation to the disease severity

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