Autism and Inflammation: Rx SOUL

Dr. Weeks’ Comment:  Over the past 3 weeks, Laura and I travelled throughout Europe and spoke with hundreds of people who told us amazing stories about how beneficial SOUL, the drink made from anti-inflammatory seeds,  has been for them. Most exciting were the stories we heard about how beneficial SOUL was for children suffering from autism spectrum disorder (ASD).  So, in order to better understand a potential mechanism of action for SOUL helping these courageous kids, I reviewed the peer-reviewed scientific literature and was gratified to learn the following:

1.

Front Neurosci. 2013 Jul 22;7:123. doi: 10.3389/fnins.2013.00123. eCollection 2013.

Autism spectrum disorder in children born preterm-role of exposure to perinatal inflammation.

Meldrum SJ, Strunk T, Currie A, Prescott SL, Simmer K, Whitehouse AJ.

Source

School of Paediatrics and Child Health, The University of Western Australia Crawley, Perth, WA, Australia ; Centre for Neonatal Research and Education, University of Western Australia Perth, WA, Australia.

Abstract

Autism Spectrum Disorder (ASD) is the collective term for neurodevelopmental disorders characterized by qualitative impairments in social interaction, communication, and a restricted range of activities and interests. Many countries, including Australia, have reported a dramatic increase in the number of diagnoses over the past three decades, with current prevalence of ASD at 1 in every 110 individuals (~1%). The potential role for an immune-mediated mechanism in ASD has been implicated by several studies, and some evidence suggests a potential link between prenatal infection-driven inflammation and subsequent development of ASD. Furthermore, a modest number of contemporary studies have reported a markedly increased prevalence of ASD in children born preterm, who are at highest risk of exposure to perinatal inflammation. However, the mechanisms that underpin the susceptibility to infection-driven inflammation during pregnancy and risk of preterm birth, and how these intersect with the subsequent development of ASD in the offspring, is not understood. This review aims to summarize and discuss the potential mechanisms and evidence for the role of prenatal infection on the central nervous system, and how it may increase the susceptibility for ASD pathogenesis in children born preterm.

KEYWORDS:

autism spectrum disorders, immunology, prenatal infection, preterm

PMID: 23885233 [PubMed] PMCID: PMC3717511 Free PMC Article

Related citations

2.

Nutrition. 2013 Oct;29(10):1175-85. doi: 10.1016/j.nut.2013.01.012. Epub 2013 Jul 30.

Autism as a disorder of deficiency of brain-derived neurotrophic factor and altered metabolism of polyunsaturated fatty acids.

Das UN.

Source

UND Life Sciences, Shaker Heights, OH, USA. Undurti@hotmail.com

Abstract

Autism has a strong genetic and environmental basis in which inflammatory markers and factors concerned with synapse formation, nerve transmission, and information processing such as brain-derived neurotrophic factor (BDNF), polyunsaturated fatty acids (PUFAs): arachidonic (AA), eicosapentaenoic (EPA), and docosahexaenoic acids (DHA) and their products and neurotransmitters: dopamine, serotonin, acetylcholine, γ-aminobutyric acid, and catecholamines and cytokines are altered. Antioxidants, vitamins, minerals, and trace elements are needed for the normal metabolism of neurotrophic factors, eicosanoids, and neurotransmitters, supporting reports of their alterations in autism. But, the exact relationship among these factors and their interaction with genes and proteins concerned with brain development and growth is not clear. It is suggested that maternal infections and inflammation and adverse events during intrauterine growth of the fetus could lead to alterations in the gene expression profile and proteomics that results in dysfunction of the neuronal function and neurotransmitters, alteration(s) in the metabolism of PUFAs and their metabolites resulting in excess production of proinflammatory eicosanoids and cytokines and a deficiency of anti-inflammatory cytokines and bioactive lipids that ultimately results in the development of autism. Based on these evidences, it is proposed that selective delivery of BDNF and methods designed to augment the production of anti-inflammatory cytokines and eicosanoids and PUFAs may prevent, arrest, or reverse the autism disease process.

Copyright © 2013 Elsevier Inc. All rights reserved.

KEYWORDS:

Autism, Brain-derived neurotrophic factor, Cytokines, Inflammation, Lipoxins, Memory, Nitric oxide, Polyunsaturated fatty acids, Prostaglandins, Resolvins

PMID: 23911220 [PubMed – in process]

Related citations

3.

Pediatr Res. 2013 Oct;74(4):393-401. doi: 10.1038/pr.2013.126. Epub 2013 Jul 22.

Maternal inflammation promotes fetal microglial activation and increased cholinergic expression in the fetal basal forebrain: role of interleukin-6.

Pratt L, Ni L, Ponzio NM, Jonakait GM.

Source

Department of Biological Sciences, Rutgers University, Newark, New Jersey.

Abstract

BACKGROUND:

Perinatal exposure to infectious agents with associated maternal immune activation (MIA) leads to neuroanatomical and behavioral dysregulation reminiscent of autism spectrum disorders. Persistent microglial activation as well as increased choline acetyltransferase (ChAT) activity in the basal forebrain (BF) are characteristic of autistic subjects. Previous studies have shown that medium from activated microglia promotes cholinergic differentiation of precursors in the BF. We sought to determine whether MIA in vivo would lead to a similar effect on developing BF neurons.

METHODS:

Pregnant mice were treated with the viral mimic polyinosinic-polycytidylic acid (poly(I:C)) or saline.

RESULTS:

Poly(I:C) treatment resulted in increased production of cytokines and chemokines in fetal microglia and increased ChAT activity and cholinergic cell number in the perinatal BF. Whether microglial activation causes these changes is unclear. Examination of fetal brains from mice lacking interleukin-6 (IL-6 KOs) revealed an elevation in non-microglial-derived cytokines and chemokines over wild-type controls. Moreover, IL-6 KO offspring showed an elevation of ChAT activity even in the absence of poly(I:C) administration.

CONCLUSION:

 

 

 

 

AND DEPRESSION TOO ??…

BMC Med. 2013 Sep 12;11:200. doi: 10.1186/1741-7015-11-200.

So depression is an inflammatory disease, but where does the inflammation come from?

Berk M, Williams LJ, Jacka FN, O’Neil A, Pasco JA, Moylan S, Allen NB, Stuart AL, Hayley AC, Byrne ML, Maes M.

Source

IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, VIC, Australia. mikebe@barwonhealth.org.au.

Abstract

BACKGROUND:

We now know that depression is associated with a chronic, low-grade inflammatory response and activation of cell-mediated immunity, as well as activation of the compensatory anti-inflammatory reflex system. It is similarly accompanied by increased oxidative and nitrosative stress (O&NS), which contribute to neuroprogression in the disorder. The obvious question this poses is ‘what is the source of this chronic low-grade inflammation?’

DISCUSSION:

This review explores the role of inflammation and oxidative and nitrosative stress as possible mediators of known environmental risk factors in depression, and discusses potential implications of these findings. A range of factors appear to increase the risk for the development of depression, and seem to be associated with systemic inflammation; these include psychosocial stressors, poor diet, physical inactivity, obesity, smoking, altered gut permeability, atopy, dental cares, sleep and vitamin D deficiency.

SUMMARY:

The identification of known sources of inflammation provides support for inflammation as a mediating pathway to both risk and neuroprogression in depression. Critically, most of these factors are plastic, and potentially amenable to therapeutic and preventative interventions. Most, but not all, of the above mentioned sources of inflammation may play a role in other psychiatric disorders, such as bipolar disorder, schizophrenia, autism and post-traumatic stress disorder.

PMID: 24228900 [PubMed – in process] Free full text

Related citations

 

 

2.

Front Neurosci. 2013 Jul 22;7:123. doi: 10.3389/fnins.2013.00123. eCollection 2013.

Autism spectrum disorder in children born preterm-role of exposure to perinatal inflammation.

Meldrum SJ, Strunk T, Currie A, Prescott SL, Simmer K, Whitehouse AJ.

Source

School of Paediatrics and Child Health, The University of Western Australia Crawley, Perth, WA, Australia ; Centre for Neonatal Research and Education, University of Western Australia Perth, WA, Australia.

Abstract

Autism Spectrum Disorder (ASD) is the collective term for neurodevelopmental disorders characterized by qualitative impairments in social interaction, communication, and a restricted range of activities and interests. Many countries, including Australia, have reported a dramatic increase in the number of diagnoses over the past three decades, with current prevalence of ASD at 1 in every 110 individuals (~1%). The potential role for an immune-mediated mechanism in ASD has been implicated by several studies, and some evidence suggests a potential link between prenatal infection-driven inflammation and subsequent development of ASD. Furthermore, a modest number of contemporary studies have reported a markedly increased prevalence of ASD in children born preterm, who are at highest risk of exposure to perinatal inflammation. However, the mechanisms that underpin the susceptibility to infection-driven inflammation during pregnancy and risk of preterm birth, and how these intersect with the subsequent development of ASD in the offspring, is not understood. This review aims to summarize and discuss the potential mechanisms and evidence for the role of prenatal infection on the central nervous system, and how it may increase the susceptibility for ASD pathogenesis in children born preterm.

KEYWORDS:

autism spectrum disorders, immunology, prenatal infection, preterm

PMID: 23885233 [PubMed] PMCID: PMC3717511 Free PMC Article

Related citations

 

 

3.

Nutrition. 2013 Oct;29(10):1175-85. doi: 10.1016/j.nut.2013.01.012. Epub 2013 Jul 30.

Autism as a disorder of deficiency of brain-derived neurotrophic factor and altered metabolism of polyunsaturated fatty acids.

Das UN.

Source

UND Life Sciences, Shaker Heights, OH, USA. Undurti@hotmail.com

Abstract

Autism has a strong genetic and environmental basis in which inflammatory markers and factors concerned with synapse formation, nerve transmission, and information processing such as brain-derived neurotrophic factor (BDNF), polyunsaturated fatty acids (PUFAs): arachidonic (AA), eicosapentaenoic (EPA), and docosahexaenoic acids (DHA) and their products and neurotransmitters: dopamine, serotonin, acetylcholine, γ-aminobutyric acid, and catecholamines and cytokines are altered. Antioxidants, vitamins, minerals, and trace elements are needed for the normal metabolism of neurotrophic factors, eicosanoids, and neurotransmitters, supporting reports of their alterations in autism. But, the exact relationship among these factors and their interaction with genes and proteins concerned with brain development and growth is not clear. It is suggested that maternal infections and inflammation and adverse events during intrauterine growth of the fetus could lead to alterations in the gene expression profile and proteomics that results in dysfunction of the neuronal function and neurotransmitters, alteration(s) in the metabolism of PUFAs and their metabolites resulting in excess production of proinflammatory eicosanoids and cytokines and a deficiency of anti-inflammatory cytokines and bioactive lipids that ultimately results in the development of autism. Based on these evidences, it is proposed that selective delivery of BDNF and methods designed to augment the production of anti-inflammatory cytokines and eicosanoids and PUFAs may prevent, arrest, or reverse the autism disease process.

Copyright © 2013 Elsevier Inc. All rights reserved.

KEYWORDS:

Autism, Brain-derived neurotrophic factor, Cytokines, Inflammation, Lipoxins, Memory, Nitric oxide, Polyunsaturated fatty acids, Prostaglandins, Resolvins

PMID: 23911220 [PubMed – in process]

Related citations

 

 

 

4.

Pediatr Res. 2013 Oct;74(4):393-401. doi: 10.1038/pr.2013.126. Epub 2013 Jul 22.

Maternal inflammation promotes fetal microglial activation and increased cholinergic expression in the fetal basal forebrain: role of interleukin-6.

Pratt L, Ni L, Ponzio NM, Jonakait GM.

Source

Department of Biological Sciences, Rutgers University, Newark, New Jersey.

Abstract

BACKGROUND:

Perinatal exposure to infectious agents with associated maternal immune activation (MIA) leads to neuroanatomical and behavioral dysregulation reminiscent of autism spectrum disorders. Persistent microglial activation as well as increased choline acetyltransferase (ChAT) activity in the basal forebrain (BF) are characteristic of autistic subjects. Previous studies have shown that medium from activated microglia promotes cholinergic differentiation of precursors in the BF. We sought to determine whether MIA in vivo would lead to a similar effect on developing BF neurons.

METHODS:

Pregnant mice were treated with the viral mimic polyinosinic-polycytidylic acid (poly(I:C)) or saline.

RESULTS:

Poly(I:C) treatment resulted in increased production of cytokines and chemokines in fetal microglia and increased ChAT activity and cholinergic cell number in the perinatal BF. Whether microglial activation causes these changes is unclear. Examination of fetal brains from mice lacking interleukin-6 (IL-6 KOs) revealed an elevation in non-microglial-derived cytokines and chemokines over wild-type controls. Moreover, IL-6 KO offspring showed an elevation of ChAT activity even in the absence of poly(I:C) administration.

CONCLUSION:

These data suggest that elevations in cytokines and/or chemokines caused either by maternal poly(I:C) administration or by the absence of IL-6 are associated with alterations in cholinergic development in the BF.

 

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Dr. Weeks’ Comment:  Over the past 3 weeks, Laura and I travelled throughout Europe and spoke with hundreds of people who told us amazing stories about how beneficial SOUL, the drink made from anti-inflammatory seeds,  has been for them. Most exciting were the stories we heard about how beneficial SOUL was for children suffering from…
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