Changes in blood-brain barrier, intestinal permeability found in individuals with autism

The group analyzed postmortem cerebral cortex and cerebellum tissues from 33 individuals - 8 with ASD, 10 with schizophrenia and 15 healthy controls. Altered expression of genes associated with blood-brain-barrier integrity and function and with inflammation was detected in ASD tissue samples, supporting the hypothesis that an impaired blood-brain barrier associated with neuroinflammation contributes to ASD.
In keeping with the hypothesis that the interplay within the gut-brain axis is a crucial component in the development of neurodevelopmental disorders, the group also analyzed intestinal epithelial tissue from 12 individuals with ASD and 9 without such disorders. That analysis revealed that 75 percent of the individuals affected by ASD had reduced expression of barrier-forming cellular components, compared with controls, and 66 percent showed a higher expression of molecules that increase intestinal permeability."

See also:-

The barrier, airway particle clearance, placental and detoxification functions of autism susceptibility genes.Pubmed

The type, not just the amount, of sugar consumption matters in risk of health problems

Female rats were given a liquid solution of either glucose (a form of sugar found naturally in the body after carbohydrates are broken down) or fructose (sugar found in fruit and fruit juices) in addition to their normal diet of solid food. The rats received the sweetened solutions for eight weeks, roughly equivalent to a person eating large amounts of sugar for six years. The sugar-fed rats were compared with a control group that received plain drinking water in addition to their food supply.
Researchers found that although both sugar-fed groups consumed more calories than the control group, the total calorie intake of the glucose-fed rats was higher than the rats that were given fructose. Another surprising observation was that "despite this difference, only the fructose group exhibited a significant increase in final body weight," wrote the research team.
In addition to higher weight gain, the fructose group showed more markers of vascular disease and liver damage than the glucose group. These included high triglycerides, increased liver weight, decreased fat burning in the liver (a factor that can contribute to fatty liver) and impaired relaxation of the aorta, which can affect blood pressure."

Food-grade TiO2 impairs intestinal and systemic immune homeostasis, initiates preneoplastic lesions and promotes aberrant crypt development in the rat colon : Scientific Reports

Food-grade titanium dioxide (TiO2) containing a nanoscale particle fraction (TiO2-NPs) is approved as a white pigment (E171 in Europe) in common foodstuffs, including confectionary. There are growing concerns that daily oral TiO2-NP intake is associated with an increased risk of chronic intestinal inflammation and carcinogenesis. In rats orally exposed for one week to E171 at human relevant levels, titanium was detected in the immune cells of Peyer’s patches (PP) as observed with the TiO2-NP model NM-105. Dendritic cell frequency increased in PP regardless of the TiO2 treatment, while regulatory T cells involved in dampening inflammatory responses decreased with E171 only, an effect still observed after 100 days of treatment. In all TiO2-treated rats, stimulation of immune cells isolated from PP showed a decrease in Thelper (Th)-1 IFN-γ secretion, while splenic Th1/Th17 inflammatory responses sharply increased. E171 or NM-105 for one week did not initiate intestinal inflammation, while a 100-day E171 treatment promoted colon microinflammation and initiated preneoplastic lesions while also fostering the growth of aberrant crypt foci in a chemically induced carcinogenesis model. These data should be considered for risk assessments of the susceptibility to Th17-driven autoimmune diseases and to colorectal cancer in humans exposed to TiO2 from dietary sources.

'via Blog this'

Scientists provide first evidence that carbamates can upset circadian rhythms

 The current research focuses on two chemicals, carbaryl, the third most widely used insecticide in the U.S. but which is illegal in several countries, and carbofuran, the most toxic carbamate insecticide, which has been banned for applications on food crops for human consumption since 2009. It is still used in many countries, including Mexico and traces persist in food, plants and wildlife.
"We found that both insecticides are structurally similar to melatonin and that both showed affinity for the melatonin, MT2 receptors, that can potentially affect glucose homeostasis and insulin secretion," said Marina Popovska-Gorevski, co-author, now a scientist with Boehringer Ingelheim Pharmaceuticals, who worked in Dubocovich's lab while earning her master's degree at UB. "That means that exposure to them could put people at higher risk for diabetes and also affect sleeping patterns.""

Many household products contain antimicrobial chemicals banned from soaps by the FDA

 Not only does research suggest that antimicrobial products are ineffective at reducing microbes on the product, but several studies also suggest they may be causing an increase in antibiotic resistance. Antibiotic-resistant infections, such as MRSA, cause an estimated 23,000 deaths every year in the United States.

Neurotoxic reactive astrocytes are induced by activated microglia : Nature : Nature Research

Reactive astrocytes are strongly induced by central nervous system (CNS) injury and disease, but their role is poorly understood. Here we show that a subtype of reactive astrocytes, which we termed A1, is induced by classically activated neuroinflammatory microglia. We show that activated microglia induce A1 astrocytes by secreting Il-1α, TNF and C1q, and that these cytokines together are necessary and sufficient to induce A1 astrocytes. A1 astrocytes lose the ability to promote neuronal survival, outgrowth, synaptogenesis and phagocytosis, and induce the death of neurons and oligodendrocytes. Death of axotomized CNS neurons in vivo is prevented when the formation of A1 astrocytes is blocked. Finally, we show that A1 astrocytes are abundant in various human neurodegenerative diseases including Alzheimer’s, Huntington’s and Parkinson’s disease, amyotrophic lateral sclerosis and multiple sclerosis. Taken together these findings help to explain why CNS neurons die after axotomy, strongly suggest that A1 astrocytes contribute to the death of neurons and oligodendrocytes in neurodegenerative disorders, and provide opportunities for the development of new treatments for these diseases.

'via Blog this'

Aluminium in brain tissue in familial Alzheimer’s disease

 The genetic predispositions which describe a diagnosis of familial Alzheimer’s disease can be considered as cornerstones of the amyloid cascade hypothesis. Essentially they place the expression and metabolism of the amyloid precursor protein as the main tenet of disease aetiology. However, we do not know the cause of Alzheimer’s disease and environmental factors may yet be shown to contribute towards its onset and progression. One such environmental factor is human exposure to aluminium and aluminium has been shown to be present in brain tissue in sporadic Alzheimer’s disease. We have made the first ever measurements of aluminium in brain tissue from 12 donors diagnosed with familial Alzheimer’s disease. The concentrations of aluminium were extremely high, for example, there were values in excess of 10 μg/g tissue dry wt. in 5 of the 12 individuals. Overall, the concentrations were higher than all previous measurements of brain aluminium except cases of known aluminium-induced encephalopathy. We have supported our quantitative analyses using a novel method of aluminium-selective fluorescence microscopy to visualise aluminium in all lobes of every brain investigated. The unique quantitative data and the stunning images of aluminium in familial Alzheimer’s disease brain tissue raise the spectre of aluminium’s role in this devastating disease.

Nanoparticle exposure reactivates latent herpesvirus and restores a signature of acute infection | Particle and Fibre Toxicology | Full Text


Inhalation of environmental (nano) particles (NP) as well as persistent herpesvirus-infection are potentially associated with chronic lung disease and as both are omnipresent in human society a coincidence of these two factors is highly likely. We hypothesized that NP-exposure of persistently herpesvirus-infected cells as a second hit might disrupt immune control of viral latency, provoke reactivation of latent virus and eventually lead to an inflammatory response and tissue damage.


To test this hypothesis, we applied different NP to cells or mice latently infected with murine gammaherpesvirus 68 (MHV-68) which provides a small animal model for the study of gammaherpesvirus-pathogenesis in vitro and in vivo. In vitro, NP-exposure induced expression of the typically lytic viral gene ORF50 and production of lytic virus. In vivo, lytic viral proteins in the lung increased after intratracheal instillation with NP and elevated expression of the viral gene ORF50 could be detected in cells from bronchoalveolar lavage. Gene expression and metabolome analysis of whole lung tissue revealed patterns with striking similarities to acute infection. Likewise, NP-exposure of human cells latently infected with Epstein-Barr-Virus also induced virus production.


Our results indicate that NP-exposure of persistently herpesvirus-infected cells – murine or human – restores molecular signatures found in acute virus infection, boosts production of lytic viral proteins, and induces an inflammatory response in the lung – a combination which might finally result in tissue damage and pathological alterations.

Variation in an Iron Metabolism Gene Moderates the Association Between Blood Lead Levels and Attention-Deficit/Hyperactivity Disorder in Children. - PubMed - NCBI

Although attention-deficit/hyperactivity disorder (ADHD) is a heritable neurodevelopmental condition, there is also considerable scientific and public interest in environmental modulators of its etiology. Exposure to neurotoxins is one potential source of perturbation of neural, and hence psychological, development. Exposure to lead in particular has been widely investigated and is correlated with neurodevelopmental outcomes, including ADHD. To investigate whether this effect is likely to be causal, we used a Mendelian randomization design with a functional gene variant. In a case-control study, we examined the association between ADHD symptoms in children and blood lead level as moderated by variants in the hemochromatosis (HFE) gene. The HFE gene regulates iron uptake and secondarily modulates lead metabolism. Statistical moderation was observed: The magnitude of the association of blood lead with symptoms of ADHD was altered by functional HFE genotype, which is consistent with a causal hypothesis."

'via Blog this'

Viruses in genome important for our brain -- ScienceDaily

"The genes that control the production of various proteins in the body represent a smaller proportion of our DNA than endogenous retroviruses. They account for approximately 2 per cent, while retroviruses account for 8-10 per cent of the total genome. If it turns out that they are able to influence the production of proteins, this will provide us with a huge new source of information about the human brain," says Johan Jakobsson.
And this is precisely what the researchers discovered. They have determined that several thousands of the retroviruses that have established themselves in our genome may serve as "docking platforms" for a protein called TRIM28. This protein has the ability to "switch off" not only viruses but also the standard genes adjacent to them in the DNA helix, allowing the presence of ERV to affect gene expression.
This switching-off mechanism may behave differently in different people, since retroviruses are a type of genetic material that may end up in different places in the genome. This makes it a possible tool for evolution, and even a possible underlying cause of neurological diseases. In fact, there are studies that indicate a deviating regulation of ERV in several neurological diseases such as ALS, schizophrenia and bipolar disorder.

Glia, not neurons, are most affected by brain aging

The difference between an old brain and a young brain isn't so much the number of neurons but the presence and function of supporting cells called glia. In Cell Reports on January 10, researchers who examined postmortem brain samples from 480 individuals ranging in age from 16 to 106 found that the state of someone's glia is so consistent through the years that it can be used to predict someone's age. The work lays the foundation to better understand glia's role in late-in-life brain disease.

Living near major roads and the incidence of dementia, Parkinson's disease, and multiple sclerosis: a population-based cohort study - The Lancet

Emerging evidence suggests that living near major roads might adversely affect cognition. However, little is known about its relationship with the incidence of dementia, Parkinson's disease, and multiple sclerosis. We aimed to investigate the association between residential proximity to major roadways and the incidence of these three neurological diseases in Ontario, Canada.


In this population-based cohort study, we assembled two population-based cohorts including all adults aged 20–50 years (about 4·4 million; multiple sclerosis cohort) and all adults aged 55–85 years (about 2·2 million; dementia or Parkinson's disease cohort) who resided in Ontario, Canada on April 1, 2001. Eligible patients were free of these neurological diseases, Ontario residents for 5 years or longer, and Canadian-born. We ascertained the individual's proximity to major roadways based on their residential postal-code address in 1996, 5 years before cohort inception. Incident diagnoses of dementia, Parkinson's disease, and multiple sclerosis were ascertained from provincial health administrative databases with validated algorithms. We assessed the associations between traffic proximity and incident dementia, Parkinson's disease, and multiple sclerosis using Cox proportional hazards models, adjusting for individual and contextual factors such as diabetes, brain injury, and neighbourhood income. We did various sensitivity analyses, such as adjusting for access to neurologists and exposure to selected air pollutants, and restricting to never movers and urban dwellers.
Between 2001, and 2012, we identified 243 611 incident cases of dementia, 31 577 cases of Parkinson's disease, and 9247 cases of multiple sclerosis. The adjusted hazard ratio (HR) of incident dementia was 1·07 for people living less than 50 m from a major traffic road (95% CI 1·06–1·08), 1·04 (1·02–1·05) for 50–100 m, 1·02 (1·01–1·03) for 101–200 m, and 1·00 (0·99–1·01) for 201–300 m versus further than 300 m (p for trend=0·0349). The associations were robust to sensitivity analyses and seemed stronger among urban residents, especially those who lived in major cities (HR 1·12, 95% CI 1·10–1·14 for people living <50 m from a major traffic road), and who never moved (1·12, 1·10–1·14 for people living <50 m from a major traffic road). No association was found with Parkinson's disease or multiple sclerosis.

In this large population-based cohort, living close to heavy traffic was associated with a higher incidence of dementia, but not with Parkinson's disease or multiple sclerosis."

'via Blog this'

Artificially Sweetened Beverages and the Response to the Global Obesity Crisis

Summary Points

In March 2015, the World Health Organization (WHO) published revised guidelines on sugar intake that call on national governments to institute policies to reduce sugar intake and increase the scope for regulation of sugar-sweetened beverages (SSBs).
In face of the growing threat of regulatory action on SSBs, transnational beverage companies are responding in multiple ways, including investing in the formulation and sales of artificially sweetened beverages (ASBs), promoted as healthier alternatives to SSBs.
The absence of consistent evidence to support the role of ASBs in preventing weight gain and the lack of studies on other long-term effects on health strengthen the position that ASBs should not be promoted as part of a healthy diet.
The promotion of ASBs must be discussed in a broader context of the additional potential impacts on health and the environment. In addition, a more robust evidence base, free of conflicts of interest, is needed."

'via Blog this'

Sunlight offers surprise benefit -- it energizes infection fighting T cells | EurekAlert! Science News

We all know sunlight provides vitamin D, which is suggested to have an impact on immunity, among other things. But what we found is a completely separate role of sunlight on immunity," says the study's senior investigator, Gerard Ahern, PhD, associate professor in the Georgetown's Department of Pharmacology and Physiology. "Some of the roles attributed to vitamin D on immunity may be due to this new mechanism.
They specifically found that low levels of blue light, found in sun rays, makes T cells move faster -- marking the first reported human cell responding to sunlight by speeding its pace.

What drove the motility response in T cells was synthesis of hydrogen peroxide, which then activated a signaling pathway that increases T cell movement. Hydrogen peroxide is a compound that white blood cells release when they sense an infection in order to kill bacteria and to "call" T cells and other immune cells to mount an immune response.

Effects of titanium dioxide nanoparticles on α-synuclein aggregation and the ubiquitin-proteasome system in dopaminergic neurons. - PubMed - NCBI

Dopaminergic neurons (PC12 cells) were treated with different doses of titanium dioxide nanoparticles (TiO2-NPs), to investigate their effects on α-Synuclein (α-Syn) aggregation and their mechanism of action. Western blotting and immunofluorescent staining were performed. Exposure to TiO2-NPs increased α-Syn expression (p < 0.05) and induced dose-dependent α-Syn aggregation. Pretreatment with N-acetylcysteine partially inhibited α-Syn expression induced by a 200 μg/ml dose of TiO2-NPs. TiO2-NPs reduced the expressions of parkin and ubiquitin C-terminal hydrolase protein, and were associated with oxidative stress in PC12 cells. Dysfunction of the ubiquitin-proteasome system also contributed to α-Syn aggregation. The potentially neurotoxic TiO2-NPs may cause Parkinson's disease

'via Blog this'

Researchers add to evidence that common bacterial cause of gum disease may drive rheumatoid arthritis -- ScienceDaily

In a report on the work, published in the Dec. 14 edition of the journal Science Translational Medicine, the investigators say the common denominator they identified in periodontal disease (gum disease) and in many people with rheumatoid arthritis is Aggregatibacter actinomycetemcomitans. An infection with A. actinomycetemcomitans appears to induce the production of citrullinated proteins, which are suspected of activating the immune system and driving the cascade of events leading to rheumatoid arthritis."

Translational Medicine paper:-

Aggregatibacter actinomycetemcomitans–induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis

Using herpes drugs to slow down Alzheimer’s disease could become reality - Umeå University, Sweden

 Umeå University researchers, led by Hugo Lövheim at the Department of Community Medicine and Rehabilitation and the Unit of Geriatric Medicine, have launched a clinical study investigating the effect of herpes drugs on Alzheimer’s disease. For four weeks, 36 people with Alzheimer’s disease will be receiving treatment with Valaciklovir, a drug which specifically targets active herpes virus. Several investigations will be made before and after the treatment to measure the effects on fundamental Alzheimer’s disease processes. Moreover, the participants will be examined with brain imaging, which together with a tracer substance accumulating in cells with active herpes virus infection could potentially detect herpes virus infection in brain cells in people with Alzheimer’s disease.

'via Blog this'

Molecular Psychiatry - Gestational vitamin D deficiency and autism-related traits: the Generation R Study

 There is intense interest in identifying modifiable risk factors associated with autism-spectrum disorders (ASD). Autism-related traits, which can be assessed in a continuous fashion, share risk factors with ASD, and thus can serve as informative phenotypes in population-based cohort studies. Based on the growing body of research linking gestational vitamin D deficiency with altered brain development, this common exposure is a candidate modifiable risk factor for ASD and autism-related traits. The association between gestational vitamin D deficiency and a continuous measure of autism-related traits at ~6 years (Social Responsiveness Scale; SRS) was determined in a large population-based cohort of mothers and their children (n=4229). 25-hydroxyvitamin D (25OHD) was assessed from maternal mid-gestation sera and from neonatal sera (collected from cord blood). Vitamin D deficiency was defined as 25OHD concentrations less than 25 nmol l−1. Compared with the 25OHD sufficient group (25OHD>50 nmol l−1), those who were 25OHD deficient had significantly higher (more abnormal) SRS scores (mid-gestation n=2866, β=0.06, P<0.001; cord blood n=1712, β=0.03, P=0.01). The findings persisted (a) when we restricted the models to offspring with European ancestry, (b) when we adjusted for sample structure using genetic data, (c) when 25OHD was entered as a continuous measure in the models and (d) when we corrected for the effect of season of blood sampling. Gestational vitamin D deficiency was associated with autism-related traits in a large population-based sample. Because gestational vitamin D deficiency is readily preventable with safe, cheap and accessible supplements, this candidate risk factor warrants closer scrutiny."

'via Blog this'

Chronology of Onset of Mental Disorders and Physical Diseases in Mental-Physical Comorbidity - A National Representative Survey of Adolescents


The objective was to estimate temporal associations between mental disorders and physical diseases in adolescents with mental-physical comorbidities.


 This article bases upon weighted data (N = 6483) from the National Comorbidity Survey Adolescent Supplement (participant age: 13–18 years), a nationally representative United States cohort. Onset of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition lifetime mental disorders was assessed with the fully structured World Health Organization Composite International Diagnostic Interview, complemented by parent report. Onset of lifetime medical conditions and doctor-diagnosed diseases was assessed by self-report.


The most substantial temporal associations with onset of mental disorders preceding onset of physical diseases included those between affective disorders and arthritis (hazard ratio (HR) = 3.36, 95%-confidence interval (CI) = 1.95 to 5.77) and diseases of the digestive system (HR = 3.39, CI = 2.30 to 5.00), between anxiety disorders and skin diseases (HR = 1.53, CI = 1.21 to 1.94), and between substance use disorders and seasonal allergies (HR = 0.33, CI = 0.17 to 0.63). The most substantial temporal associations with physical diseases preceding mental disorders included those between heart diseases and anxiety disorders (HR = 1.89, CI = 1.41 to 2.52), epilepsy and eating disorders (HR = 6.27, CI = 1.58 to 24.96), and heart diseases and any mental disorder (HR = 1.39, CI = 1.11 to 1.74).


 Findings suggest that mental disorders are antecedent risk factors of certain physical diseases in early life, but also vice versa. Our results expand the relevance of mental disorders beyond mental to physical health care, and vice versa, supporting the concept of a more integrated mental-physical health care approach, and open new starting points for early disease prevention and better treatments, with relevance for various medical disciplines."

'via Blog this'

Dad's exposure to phthalates in plastics may affect embryonic development

A new study led by environmental health scientist Richard Pilsner at the University of Massachusetts Amherst, one of the first to investigate whether preconception exposures to phthalates in fathers has an effect on reproductive success via embryo quality, found that exposures from select chemicals tested were associated with "a pronounced decrease in blastocyst quality" at an early stage in embryo development.

Phthalates are compounds found in plastics and personal care products that are estimated to be detectable in nearly 100 percent of the U.S. population. The authors believe theirs is the first prospective study to assess associations between paternal exposure to  and embryo quality through the blastocyst stage in humans.
Pilsner and colleagues say their prospective study of 761 oocytes, or immature eggs, from 50 couples undergoing in vitro fertilization (IVF) "provides the first data demonstrating associations between preconception paternal phthalate and phthalate alternatives and , in a critical step towards our understanding of the paternal contributions to reproductive success." Details appear in the current issue of Human Reproduction from Oxford University Press.

Parental contributions to early embryo development: influences of urinary phthalate and phthalate alternatives among couples undergoing IVF treatment