How severe maternal inflammation can lead to autism-like behavior: Immune molecules in infected mothers tied to brain and behavior abnormalities in offspring -- ScienceDaily

"A group of researchers found that immune cells activated in the mother during severe inflammation produce an immune effector molecule called IL-17 that appears to interfere with brain development."



'via Blog this'

Food additive that may prevent skin cancer revealed by scientists: Unlike sunscreen, the nutritional compound protects skin from the inside out -- ScienceDaily

"Researchers at the University of Arizona College of Pharmacy have discovered that a compound found in the natural food additive annatto prevents the formation of cancer cells and skin damage from UV radiation in mice. In the future the compound, bixin, may be valuable in the prevention and treatment of human skin cancers."



'via Blog this'

Schizophrenia and the Synapse | The Scientist Magazine®

Compared to the brains of healthy individuals, those of people with schizophrenia have higher expression of a gene called Complement C4, according to a paper published in Nature today (January 27). The gene encodes an immune protein that moonlights in the brain as an eradicator of unwanted neural connections (synapses). The findings, which suggest increased synaptic pruning is a feature of the disease, are a direct extension of genome-wide association studies (GWASs) that pointed to the major histocompatibility (MHC) locus as a key region associated with schizophrenia risk.

Protective Effect of Amyloid-β Peptides Against Herpes Simplex Virus-1 Infection in a Neuronal Cell Culture Model - IOS Press

Senile amyloid plaques are one of the main hallmarks of Alzheimer’s disease (AD). They correspond to insoluble deposits of amyloid-β peptides (Aβ) and are responsible for the inflammatory response and neurodegeneration that lead to loss of memory. Recent data suggest that Aβ possess antimicrobial and anti-viral activity in vitro. Here, we have used cocultures of neuroglioma (H4) and glioblastoma (U118-MG) cells as a minimal in vitro model to investigate whether Aβ is produced by neuroglioma cells and whether this could result in protective anti-viral activity against HSV-1 infection. Results showed that H4 cells secreted Aβ 42 in response to HSV-1 challenge and that U118-MG cells could rapidly internalize Aβ 42. Production of pro-inflammatory cytokines TNFα and IL-1β by H4 and U118-MG cells occurred under basal conditions but infection of the cells with HSV-1 did not significantly upregulate production. Both cell lines produced low levels of IFNα. However, extraneous Aβ 42 induced strong production of these cytokines. A combination of Aβ 42 and HSV-1 induced production of pro-inflammatory cytokines TNFα and IL-1β, and IFNα in the cell lines. The reported anti-viral protection of Aβ 42 was revealed in transfer experiments involving conditioned medium (CM) of HSV-1-infected H4 cells. CM conferred Aβ-dependent protection against HSV-1 replication in de novo cultures of H4 cells challenged with HSV-1. Type 1 interferons did not play a role in these assays. Our data established that H4 neuroglioma cells produced Aβ 42 in response to HSV-1 infection thus inhibiting secondary replication. This mechanism may play a role in the etiology of AD.

How a food packaging chemical could lead to weight gain - Medical News Today

"Martin von Bergen, head of the Department of Molecular Systems Biology at the Helmholtz Centre for Environmental Research (UFZ) in Germany, and colleagues found that the chemical di-(2-ethylhexyl)-phthalate (DEHP) led to a hormone imbalance in female mice that triggered weight gain, even when exposed to the chemical in low concentrations."


Dietary exposure to an environmental toxin triggers neurofibrillary tangles and amyloid deposits in the brain | Proceedings of the Royal Society of London B: Biological Sciences

Neurofibrillary tangles (NFT) and β-amyloid plaques are the neurological hallmarks of both Alzheimer's disease and an unusual paralytic illness suffered by Chamorro villagers on the Pacific island of Guam. Many Chamorros with the disease suffer dementia, and in some villages one-quarter of the adults perished from the disease. Like Alzheimer's, the causal factors of Guamanian amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC) are poorly understood. In replicated experiments, we found that chronic dietary exposure to a cyanobacterial toxin present in the traditional Chamorro diet, β-N-methylamino-L-alanine (BMAA), triggers the formation of both NFT and β-amyloid deposits similar in structure and density to those found in brain tissues of Chamorros who died with ALS/PDC. Vervets (Chlorocebus sabaeus) fed for 140 days with BMAA-dosed fruit developed NFT and sparse β-amyloid deposits in the brain. Co-administration of the dietary amino acid L-serine with L-BMAA significantly reduced the density of NFT. These findings indicate that while chronic exposure to the environmental toxin BMAA can trigger neurodegeneration in vulnerable individuals, increasing the amount of L-serine in the diet can reduce the risk.

Maternal Consumption of Seafood in Pregnancy and Child Neuropsychological Development: A Longitudinal Study Based on a Population With High Consump... - PubMed - NCBI

Seafood consumption during pregnancy is thought to be beneficial for child neuropsychological development, but to our knowledge no large cohort studies with high fatty fish consumption have analyzed the association by seafood subtype. We evaluated 1,892 and 1,589 mother-child pairs at the ages of 14 months and 5 years, respectively, in a population-based Spanish birth cohort established during 2004-2008. Bayley and McCarthy scales and the Childhood Asperger Syndrome Test were used to assess neuropsychological development. Results from multivariate linear regression models were adjusted for sociodemographic characteristics and further adjusted for umbilical cord blood mercury or long-chain polyunsaturated fatty acid concentrations. Overall, consumption of seafood above the recommended limit of 340 g/week was associated with 10-g/week increments in neuropsychological scores. By subtype, in addition to lean fish, consumption of large fatty fish showed a positive association; offspring of persons within the highest quantile (>238 g/week) had an adjusted increase of 2.29 points in McCarthy general cognitive score (95% confidence interval: 0.42, 4.16). Similar findings were observed for the Childhood Asperger Syndrome Test. Beta coefficients diminished 15%-30% after adjustment for mercury or long-chain polyunsaturated fatty acid concentrations. Consumption of large fatty fish during pregnancy presents moderate child neuropsychological benefits, including improvements in cognitive functioning and some protection from autism-spectrum traits.

BBC One - Panorama, Can You Stop My Multiple Sclerosis?

One hundred thousand people in the UK have multiple sclerosis, an incurable condition that can result in permanent disability. Panorama has exclusive access to patients pioneering a crossover cancer treatment that has enabled some MS sufferers with paralysis to regain their movement.

News fron the Royal Hallamshire Hospital 

On Monday 18 January, a pioneering treatment for Multiple Sclerosis (MS) developed at Sheffield Teaching Hospitals will be featured on BBC Panorama. The programme aired at 8:30pm and called “Can you stop my Multiple Sclerosis?” follows four patients with relapsing/remitting MS and tells their remarkable stories. The treatment, which is called autologous haematopoietic stem cell transplantation (AHSCT) destroys the faulty immune system using chemotherapy. It is then rebuilt with stem cells harvested from the patient's own blood; these cells are at such an early stage they've not developed the flaws that trigger MS. The groundbreaking treatment involves collecting the patient’s own bone marrow stem cells and freezing them. The patient is then given a high dose of chemotherapy before the stem cells are thawed and re-infused into the patient’s blood to reboot their immune system. Prof John Snowden, Consultant Haematologist, Royal Hallamshire Hospital said: "The immune system is being reset or rebooted back to a time point before it caused MS." Around 20 patients have been treated to date at the Royal Hallamshire Hospital in Sheffield. Professor Basil Sharrack, Consultant Neurologist at Sheffield Teaching Hospital’s NHS Foundation Trust, said: “The new treatment is showing some REMARKABLE results in the small number of patients we have treated so far. It is important to stress however that this treatment is unfortunately not suitable for everyone. The treatment is only suitable for patients with relapsing remitting multiple sclerosis disease who have had two or more significant relapses in the previous twelve months, failed to respond to standard drug treatment and who have had the illness for no more than 10 years. This treatment is not effective in patients with primary or secondary MS. These initial results need to be confirmed on a much larger scale and over a longer period. That is why we are taking part in a major international clinical research trial - MIST - together with hospitals in the United States, Sweden and Brazil - which is assessing the long-term benefits of this treatment.” Around 100,000 people in the UK have the incurable condition that causes a person’s immune system to attack the nerve fibres and their lining in the brain and spinal cord. The team from BBC Panorama were given exclusive access to follow four of Sheffield’s patients to receive the new treatment. Professor John Snowden said: “The treatment has been developed thanks to a unique partnership we have here at the Royal Hallamshire Hospital between the neurology and haematology departments. The treatment has traditionally been used to treat bone and blood cancers.” Holly Drewry, one of the patients who were treated at the Royal Hallamshire Hosiptal in Sheffield, could only dream of walking to the shops with her daughter Isla. Now, thanks to this pioneering stem cell treatment, that dream has become a reality. Holly said: "It's been amazing. I got my life and my independence back and the future is bright again in terms of being a mum and doing everything with Isla." Two years on she has suffered no relapses and there is currently no evidence of active disease on her scans

CJD and Scrapie Require Agent-Associated Nucleic Acids for Infection. - PubMed - NCBI

Unlike Alzheimer's and other neurodegenerative diseases, Transmissible Spongiform Encephalopathies (TSEs) are all caused by actively replicating infectious particles of viral size and density. Different strain-specific TSE agents cause CJD, kuru, scrapie, and BSE, and all behave as latent viruses that evade adaptive immune responses and can persist for years in lymphoreticular tissues. A foreign viral structure with a nucleic acid genome best explains these TSE strains and their endemic and epidemic spread in susceptible species. Nevertheless, it is widely believed that host prion protein (PrP), without any genetic material, encodes all these strains. We developed rapid infectivity assays that allowed us to reproducibly isolate infectious particles where >85% of the starting titer separated from the majority of host components, including PrP. Remarkably, digestion of all forms of PrP did not reduce brain particle titers. To ask if TSE agents, as other viruses, require nucleic acids, we exposed high titer FU-CJD and 22L scrapie particles to potent nucleases. Both agent-strains were propagated in GT1 neuronal cells to avoid interference by complex degenerative brain changes that can impede nuclease digestions. After exposure to nucleases that are active in sarkosyl, infectivity of both agents was reproducibly reduced by >99%. No gold-stained host proteins or any form of PrP were visibly altered by these nucleases. In contrast, co-purifying protected mitochondrial DNA and circular SPHINX DNAs were destroyed. These findings demonstrate that TSE agents require protected genetic material to infect their hosts, and should open reinvestigation of essential agent nucleic acids.

Inhalation of Polychlorinated Biphenyls (PCB) Produces Hyperactivity in Rats. - PubMed - NCBI

Attention deficit hyperactivity disorder (ADHD) is a serious behavioral syndrome seen in children, and more common in males than females. There is increasing evidence that prenatal and/or early life exposure to persistent organic pollutants (POP) such as polychlorinated biphenyls (PCB) is associated with increased risk of ADHD occurrence. While PCB exposure is usually attributed to ingestion of contaminated food, recent reports of elevated PCB concentrations in indoor air, especially in schools, raised concern regarding inhalation as an important route of exposure to PCB with consequent effects on neurobehavior. The effects of exposure to air contaminated with Aroclor 1248 or contaminated sediment (SED) from the St. Lawrence River were examined on operant behavior of male and female Sprague-Dawley rats. Data showed that relative to controls, vapor-phase inhalation of PCB, whether from blowing air over Aroclor 1248 or from blowing air over sediment contaminated with PCB, resulted in hyperactivity and impatience in rats, more pronounced in males than females. These results are consistent with the hypothesis that inhalation of PCB may contribute to behavioral abnormalities in children.

Evidence for fungal infection in cerebrospinal fluid and brain tissue from patients with amyotrophic lateral sclerosis. - PubMed - NCBI

 "Among neurogenerative diseases, amyotrophic lateral sclerosis (ALS) is a fatal illness characterized by a progressive motor neuron dysfunction in the motor cortex, brainstem and spinal cord. ALS is the most common form of motor neuron disease; yet, to date, the exact etiology of ALS remains unknown. In the present work, we have explored the possibility of fungal infection in cerebrospinal fluid (CSF) and in brain tissue from ALS patients. Fungal antigens, as well as DNA from several fungi, were detected in CSF from ALS patients. Additionally, examination of brain sections from the frontal cortex of ALS patients revealed the existence of immunopositive fungal antigens comprising punctate bodies in the cytoplasm of some neurons. Fungal DNA was also detected in brain tissue using PCR analysis, uncovering the presence of several fungal species. Finally, proteomic analyses of brain tissue demonstrated the occurrence of several fungal peptides. Collectively, our observations provide compelling evidence of fungal infection in the ALS patients analyzed, suggesting that this infection may play a part in the etiology of the disease or may constitute a risk factor for these patients."



'via Blog this'

RNA Epigenetics | The Scientist Magazine®

 "For years, researchers described DNA and RNA as linear chains of four building blocks—the nucleotides A, G, C, and T for DNA; and A, G, C, and U for RNA. But these information molecules are much more than their core sequences. A variety of chemical modifications decorate the nucleic acids, increasing the alphabet of DNA to about a dozen known nucleotide variants. The alphabet of RNA is even more impressive, consisting of at least 140 alternative nucleotide forms. The different building blocks can affect the complementarity of the RNA molecules, alter their structure, and enable the binding of specific proteins that mediate various biochemical and cellular outcomes."



'via Blog this'

Alzheimer's Disease Variants with the Genome-Wide Significance are Significantly Enriched in Immune Pathways and Active in Immune Cells. - PubMed - NCBI

The existing large-scale genome-wide association studies (GWAS) datasets provide strong support for investigating the mechanisms of Alzheimer's disease (AD) by applying multiple methods of pathway analysis. Previous studies using selected single nucleotide polymorphisms (SNPs) with several thresholds of nominal significance for pathway analysis determined that the threshold chosen for SNPs can reflect the disease model. Presumably, then, pathway analysis with a stringent threshold to define "associated" SNPs would test the hypothesis that highly associated SNPs are enriched in one or more particular pathways. Here, we selected 599 AD variants (P < 5.00E-08) to investigate the pathways in which these variants are enriched and the cell types in which these variants are active. Our results showed that AD variants are significantly enriched in pathways of the immune system. Further analysis indicated that AD variants are significantly enriched for enhancers in a number of cell types, in particular the B-lymphocyte, which is the most substantially enriched cell type. This cell type maintains its dominance among the strongest enhancers. AD SNPs also display significant enrichment for DNase in 12 cell types, among which the top 6 significant signals are from immune cell types, including 4 B cells (top 4 significant signals) and CD14+ and CD34+ cells. In summary, our results show that these AD variants with P < 5.00E-08 are significantly enriched in pathways of the immune system and active in immune cells. To a certain degree, the genetic predisposition for development of AD is rooted in the immune system, rather than in neuronal cells.

Physical activity and genetic predisposition to obesity in a multiethnic longitudinal study. - PubMed - NCBI

Physical activity (PA) has been shown to reduce the impact of FTO variation and obesity genetic risk scores (GRS) on BMI. We examined this interaction using a quantitative measure of PA and two adiposity indexes in a longitudinal multi-ethnic study. We analyzed the impact of PA on the association between 14 obesity predisposing variants (analyzed independently and as a GRS) and baseline/follow-up obesity measures in the multi-ethnic prospective cohort EpiDREAM (17423 participants from six ethnic groups). PA was analyzed using basic (low-moderate-high) and quantitative measures (metabolic equivalents (METS)), while BMI and the body adiposity index (BAI) were used to measure obesity. Increased PA was associated with decreased BMI/BAI at baseline/follow-up. FTO rs1421085, CDKAL1 rs2206734, TNNl3K rs1514176, GIPR rs11671664 and the GRS were associated with obesity measures at baseline and/or follow-up. Risk alleles of three SNPs displayed nominal associations with increased (NTRK2 rs1211166, BDNF rs1401635) or decreased (NPC1 rs1805081) basic PA score independently of BMI/BAI. Both basic and quantitative PA measures attenuated the association between FTO rs1421085 risk allele and BMI/BAI at baseline and follow-up. Our results show that physical activity can blunt the genetic effect of FTO rs1421085 on adiposity by 36-75% in a longitudinal multi-ethnic cohort.

Toxins found in fracking fluids and wastewater, study shows -- ScienceDaily

"In an analysis of more than 1,000 chemicals in fluids used in and created by hydraulic fracturing (fracking), researchers found that many of the substances have been linked to reproductive and developmental health problems, and the majority had undetermined toxicity due to insufficient information."
157 of them -- chemicals such as arsenic, benzene, cadmium, lead, formaldehyde, chlorine, and mercury -- were associated with either developmental or reproductive toxicity. Of these, 67 chemicals were of particular concern because they had an existing federal health-based standard or guideline, said the scientists, adding that data on whether levels of chemicals exceeded the guidelines were too limited to assess.



'via Blog this'

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.

In utero Exposure to β-2-Adrenergic Receptor Agonist Drugs and Risk for Autism Spectrum Disorders. - PubMed - NCBI

The purpose of this study was to investigate associations between use of β-2-adrenergic receptor (B2AR) agonist drugs during pregnancy and risk for autism spectrum disorders (ASD).

METHODS:

A case-control study was conducted by using Denmark's health and population registers. Among children born between 1997 and 2006, 5200 cases with ASD admission diagnoses and 52 000 controls without ASD were identified and individually matched on month and year of birth. Conditional logistic regression models were used to estimate odds ratios (OR) and confidence intervals (CI) for any B2AR agonist exposure during pregnancy, preconception, and by trimester.

RESULTS:

In total, 3.7% of cases and 2.9% of controls were exposed to B2ARs during pregnancy. Use of B2ARs during pregnancy was associated with increased risk of ASD, even after adjustment for maternal asthma and other covariates (OR: 1.3, 95% CI: 1.1-1.5). The elevated risk was observed with use of B2AR during preconception (OR: 1.3, 95% CI: 1.0-1.6), first trimester (OR: 1.3, 95% CI: 1.1-1.5), second trimester (OR: 1.5, 95% CI: 1.1-1.7), and the third trimester (OR: 1.4, 95% CI: 1.1-1.7). There was some evidence that longer B2AR within-pregnancy use was associated with the increased risk.

CONCLUSIONS:

B2AR agonist exposure during pregnancy may be associated with an increased risk for ASD. If the effect is real, any intervention must be balanced against benefits of indicated medication use by pregnant women.

Nature Brain disorders across the lifespan

Brain and other nervous-system disorders impose a disproportionate burden on those in low- and middle-income countries. For over a decade, the Fogarty International Center and its NIH partners have supported research and capacity-building to provide context-sensitive solutions to this public health challenge. This supplement outlines the overarching and intersecting research priorities for addressing causes, prevention, treatment and rehabilitation, as well as opportunities to strengthen scientific capacity that can promote global nervous system health."

Free open access supplement:

Disease-Linked Genes Questioned | The Scientist Magazine®


Cat scratches, not bites, are associated with unipolar depression - cross-sectional study. - PubMed - NCBI

 A recent study performed on 1.3 million patients showed a strong association between being bitten by a cat and probability of being diagnosed with depression. Authors suggested that infection with cat parasite Toxoplasma could be the reason for this association.

METHOD:

A cross sectional internet study on a non-clinical population of 5,535 subjects was undertaken.

RESULTS:

The subjects that reported having been bitten by a dog and a cat or scratched by a cat have higher Beck depression score. They were more likely to have visited psychiatrists, psychotherapists and neurologists in past two years, to have been previously diagnosed with depression (but not with bipolar disorder). Multivariate analysis of models with cat biting, cat scratching, toxoplasmosis, the number of cats at home, and the age of subjects as independent variables showed that only cat scratching had positive effect on depression (p = 0.004). Cat biting and toxoplasmosis had no effect on the depression, and the number of cats at home had a negative effect on depression (p = 0.021).

CONCLUSIONS:

Absence of association between toxoplasmosis and depression and five times stronger association of depression with cat scratching than with cat biting suggests that the pathogen responsible for mood disorders in animals-injured subjects is probably not the protozoon Toxoplasma gondii but another organism; possibly the agent of cat-scratched disease - the bacteria Bartonella henselae.