A Pilot Proteomic Analysis of Salivary Biomarkers in Autism Spectrum Disorder - Ngounou Wetie - 2015 - Autism Research - Wiley Online Library

Autism spectrum disorder (ASD) prevalence is increasing, with current estimates at 1/68–1/50 individuals diagnosed with an ASD. Diagnosis is based on behavioral assessments. Early diagnosis and intervention is known to greatly improve functional outcomes in people with ASD. Diagnosis, treatment monitoring and prognosis of ASD symptoms could be facilitated with biomarkers to complement behavioral assessments. Mass spectrometry (MS) based proteomics may help reveal biomarkers for ASD. In this pilot study, we have analyzed the salivary proteome in individuals with ASD compared to neurotypical control subjects, using MS-based proteomics. Our goal is to optimize methods for salivary proteomic biomarker discovery and to identify initial putative biomarkers in people with ASDs. The salivary proteome is virtually unstudied in ASD, and saliva could provide an easily accessible biomaterial for analysis. Using nano liquid chromatography-tandem mass spectrometry, we found statistically significant differences in several salivary proteins, including elevated prolactin-inducible protein, lactotransferrin, Ig kappa chain C region, Ig gamma-1 chain C region, Ig lambda-2 chain C regions, neutrophil elastase, polymeric immunoglobulin receptor and deleted in malignant brain tumors 1. Our results indicate that this is an effective method for identification of salivary protein biomarkers, support the concept that immune system and gastrointestinal disturbances may be present in individuals with ASDs and point toward the need for larger studies in behaviorally-characterized individuals.

Obesity, diabetes symptoms in mice improved by reversing brain inflammation -- ScienceDaily

 "Using an antioxidant to reverse inflammation in the brain caused by a high-fat diet greatly improves symptoms related to obesity and type 2 diabetes, a new study suggests. The research suggests that butein and other natural compounds that block inflammation in the brain should be vigorously investigated as novel anti-diabetic treatments, he says."
Dr Tups says the study adds to growing body of evidence that a diet high in saturated fats activates a cascade of inflammatory processes in the brain which impair leptin and insulin signalling, leading to obesity and type II diabetes.
"Our findings strongly support this idea and we also show that reversing this inflammation promotes a return towards normal metabolic functioning," he says.
The research suggests that butein and other natural compounds that block inflammation in the brain should be vigorously investigated as novel anti-diabetic treatments, he says.





Added fructose is a principal driver of type 2 diabetes, experts argue -- ScienceDaily


Common pesticide may increase risk of ADHD

The research published Wednesday in theJournal of the Federation of American Societies for Experimental Biology (FASEB J.), by Rutgers scientists and colleagues from Emory University, the University of Rochester Medical Center, and Wake Forest University discovered that mice exposed to the pyrethroid pesticide deltamethrin in utero and through lactation exhibited several features of ADHD, including dysfunctional dopamine signaling in the brain, hyperactivity, working memory, attention deficits and impulsive-like behavior.

Severe depression linked with inflammation in the brain - Medical News Today

Researchers from the Centre for Addiction and Mental Health's (CAMH) Campbell Family Mental Health Research Institute in Toronto, Canada, used positron emission tomography (PET) to scan the brains of 20 patients with depression and 20 healthy control participants.

In particular, the team closely measured the activation of microglia - immune cells that play a key role in the brain's inflammatory response

The PET scans showed significant inflammation in the brains of the people with depression, and the inflammation was most severe among the participants with the most severe depression. The brains of people who were experiencing clinical depression exhibited an inflammatory increase of 30%.

Previous studies have examined markers of inflammation in the blood of depressed people, in an attempt to solve the "chicken or egg" debate of whether inflammation is a consequence of or contributor to major depression.


Related articles 


Autoimmune diseases and severe infections as risk factors for mood disorders: a nationwide study.



JAMA Internal Medicine | Cumulative Use of Strong Anticholinergics and Incident Dementia:  A Prospective Cohort Study

Importance  Many medications have anticholinergic effects. In general, anticholinergic-induced cognitive impairment is considered reversible on discontinuation of anticholinergic therapy. However, a few studies suggest that anticholinergics may be associated with an increased risk for dementia.
Objective  To examine whether cumulative anticholinergic use is associated with a higher risk for incident dementia.
Design, Setting, and Participants  Prospective population-based cohort study using data from the Adult Changes in Thought study in Group Health, an integrated health care delivery system in Seattle, Washington. We included 3434 participants 65 years or older with no dementia at study entry. Initial recruitment occurred from 1994 through 1996 and from 2000 through 2003. Beginning in 2004, continuous replacement for deaths occurred. All participants were followed up every 2 years. Data through September 30, 2012, were included in these analyses.
Exposures  Computerized pharmacy dispensing data were used to ascertain cumulative anticholinergic exposure, which was defined as the total standardized daily doses (TSDDs) dispensed in the past 10 years. The most recent 12 months of use was excluded to avoid use related to prodromal symptoms. Cumulative exposure was updated as participants were followed up over time.
Main Outcomes and Measures  Incident dementia and Alzheimer disease using standard diagnostic criteria. Statistical analysis used Cox proportional hazards regression models adjusted for demographic characteristics, health behaviors, and health status, including comorbidities.
Results  The most common anticholinergic classes used were tricyclic antidepressants, first-generation antihistamines, and bladder antimuscarinics. During a mean follow-up of 7.3 years, 797 participants (23.2%) developed dementia (637 of these [79.9%] developed Alzheimer disease). A 10-year cumulative dose-response relationship was observed for dementia and Alzheimer disease (test for trend, P < .001). For dementia, adjusted hazard ratios for cumulative anticholinergic use compared with nonuse were 0.92 (95% CI, 0.74-1.16) for TSDDs of 1 to 90; 1.19 (95% CI, 0.94-1.51) for TSDDs of 91 to 365; 1.23 (95% CI, 0.94-1.62) for TSDDs of 366 to 1095; and 1.54 (95% CI, 1.21-1.96) for TSDDs greater than 1095. A similar pattern of results was noted for Alzheimer disease. Results were robust in secondary, sensitivity, and post hoc analyses.
Conclusions and Relevance  Higher cumulative anticholinergic use is associated with an increased risk for dementia. Efforts to increase awareness among health care professionals and older adults about this potential medication-related risk are important to minimize anticholinergic use over time.

Study suggests sleeping drugs can increase risk of Alzheimer’s | Society | The Guardian

Over-the-counter sleeping aids and hayfever treatments can increase the risk of Alzheimer’s disease, a study has found. The sleeping medication Nytol and anti-allergy pills Benadryl and Piriton all belong to a class of drug highlighted in a warning from researchers.
Each of these drugs has “anticholinergic” blocking effects on the nervous system that are said – at higher doses – to raise the likelihood of developing Alzheimer’s and other forms of dementia significantly over several years.
Other drugs on the risk list include older “tricyclic” antidepressants such as doxepin, and the bladder control treatment Ditropan (oxybutynin). Many of these medicines are taken by vulnerable older people, according to the scientists, who say their findings have public health implications.

Whole-genome sequencing of quartet families with autism spectrum disorder : Nature Medicine : Nature Publishing Group

Autism spectrum disorder (ASD) is genetically heterogeneous, with evidence for hundreds of susceptibility loci. Previous microarray and exome-sequencing studies have examined portions of the genome in simplex families (parents and one ASD-affected child) having presumed sporadic forms of the disorder. We used whole-genome sequencing (WGS) of 85 quartet families (parents and two ASD-affected siblings), consisting of 170 individuals with ASD, to generate a comprehensive data resource encompassing all classes of genetic variation (including noncoding variants) and accompanying phenotypes, in apparently familial forms of ASD. By examining de novo and rare inherited single-nucleotide and structural variations in genes previously reported to be associated with ASD or other neurodevelopmental disorders, we found that some (69.4%) of the affected siblings carried different ASD-relevant mutations. These siblings with discordant mutations tended to demonstrate more clinical variability than those who shared a risk variant. Our study emphasizes that substantial genetic heterogeneity exists in ASD, necessitating the use of WGS to delineate all genic and non-genic susceptibility variants in research and in clinical diagnostics.

Effect of BPA and estradiol on sperm development seen by researchers -- ScienceDaily

"A direct link between the plastics component bisphenol A, or BPA, and disrupted sperm production has been discovered by researchers. They say the chemical disrupts the delicate DNA interactions needed to create sperm. This work may have unearthed the physiological mechanism that could account for decreased sperm counts seen in several human studies."
In addition to seeing BPA effects, Hunt and her colleagues saw an even larger effect on sperm by estradiol, the birth control hormone that passes untreated through sewage plants.
Hunt has a long history of working with BPA, which is often found in plastic bottles, the linings of food and beverage cans, and thermal receipts. Much of her work has documented its effect on female reproduction, from mice to monkeys.
Declining sperm counts have been a subject of concern and conjecture since the early 1990s, when Danish researchers reported "a genuine decline in semen quality over the past 50 years," with possible implications for male fertility. Sperm count studies have often been criticized for being small, having biased populations or questionable statistical methods, but reproductive biologists continue to see data suggesting that endocrine disruptors like BPA, plastic-softening phthalates and estradiol are impairing reproduction. In a 2013 study cited by Hunt and her colleagues, French researchers looked at the partners of more than 26,000 infertile women and saw their semen concentration drop nearly 2 percent a year for 17 years.






Viruses may play unexpected role in inflammatory bowel diseases

"Inflammatory bowel diseases are associated with a decrease in the diversity of bacteria in the gut, but a new study led by researchers at Washington University School of Medicine in St. Louis has linked the same illnesses to an increase in the diversity of viruses.

The scientists found that patients with inflammatory bowel diseases had a greater variety of viruses in their digestive systems than healthy volunteers, suggesting viruses likely play a role in the diseases"

First Evidence of Potential Efficacy of Tau Aggregation Inhibitor Therapy in Alzheimer’s Disease — TauRx

ABERDEEN, Scotland and SINGAPORE, 20 January 2015 – The Journal of Alzheimer’s Disease has published today the results of the first clinical trial of a Tau Aggregation Inhibitor (TAI) in Alzheimer’s disease (AD).1 This Phase II clinical trial, conducted by TauRx Therapeutics Ltd (a Singapore incorporated spinout from the University of Aberdeen), provided the basis and rationale for subsequent Phase III clinical trials of a TAI in AD currently in progress.

The double-blind dose-finding Phase II clinical trial involved 321 patients in 16 clinical research centres in the UK and one centre in Singapore and tested three doses of the drug (Methylene blue) . The study met its predefined primary efficacy endpoint at 24 weeks on the standard scale most commonly used to measure cognitive decline in clinical trials (ADAS-cog) at the 138 mg / day dose. The primary result was also supported by benefit on two other clinical scales. The effect sizes seen were statistically significant and clinically meaningful in moderate subjects at 24 weeks. The clinical results were also supported by brain scan evidence of arrest of decline over the same period in mild subjects at the same dose. The beneficial effect was sustained to 50 weeks in both mild and moderate subjects at this dose, with 90% reduction in the rate of cognitive decline overall.

Hepatitis C virus infection: a risk factor for Parkinson's disease. - PubMed - NCBI

Recent studies found that hepatitis C virus (HCV) may invade the central nervous system, and both HCV and Parkinson's disease (PD) have in common the overexpression of inflammatory biomarkers. We analysed data from a community-based integrated screening programme based on a total of 62 276 subjects. We used logistic regression models to investigate association between HCV infection and PD. The neurotoxicity of HCV was evaluated in the midbrain neuron-glia coculture system in rats. The cytokine/chemokine array was performed to measure the differences of amounts of cytokines released from midbrain in the presence and absence of HCV. The crude odds ratios (ORs) for having PD were 0.62 [95% confidence interval (CI), 0.48-0.81] and 1.91 (95% CI, 1.48-2.47) for hepatitis B virus (HBV) and HCV. After controlling for potential confounders, the association between HCV and PD remained statistically significant (adjusted OR = 1.39; 95% CI, 1.07-1.80), but not significantly different between HBV and PD. The HCV induced 60% dopaminergic neuron death in the midbrain neuron-glia coculture system in rats, similar to that of 1-methyl-4-phenylpyridinium (MPP+ ) but not caused by HBV. This link was further supported by the finding that HCV infection may release the inflammatory cytokines, which may play a role in the pathogenesis of PD. In conclusion, our study demonstrated a significantly positive epidemiological association between HCV infection and PD and corroborated the dopaminergic toxicity of HCV similar to that of MPP+ 

Blood vessels in older brains break down, possibly leading to Alzheimer's -- ScienceDaily

"University of Southern California (USC) neuroscientists may have unlocked another puzzle to preventing risks that can lead to Alzheimer's disease. Researchers at Keck Medicine of USC used high-resolution imaging of the living human brain to show for the first time that the brain's protective blood barrier becomes leaky with age, starting at the hippocampus, a critical learning and memory center that is damaged by Alzheimer's disease."


BPA exposure during pregnancy causes oxidative stress in child, mother

"Researchers analyzed blood samples from 24 mother and infant pairs to examine the effects of BPA exposure. The women had blood drawn during the first trimester of pregnancy to measure their BPA levels. The women were divided into two groups - those who had lower levels of BPA in their blood, and those who had higher levels. Researchers also took blood samples from the umbilical cords after the babies were delivered and measured the amount of chemical byproducts created by oxidative stress.
The blood analysis revealed that the human mothers exposed to higher levels of BPA and their infants showed signs of oxidative stress caused by overexposure to nitric oxide-derived free radicals. The study participants had larger amounts of byproducts caused by this type of oxidative damage in their blood.
In addition to the human subjects, the researchers studied the effects of BPA on pregnancy in sheep, rats and mice. The scientists fed animals diets containing either high or low doses of BPA. The researchers then measured the resulting oxidative stress on the mothers and their offspring using blood samples. The results corroborated the results in the human study."




Dementia rates higher for people in the north than the south - Medical News Today

How far north a person lives could influence their risk of developing dementia, a study suggests.
Researchers say that a higher occurrence of dementia among people living in northern parts of Scotland and Sweden suggests that environmental factors - such as levels of sunlight - may influence adults' risk of developing the disease.
Scientists say that the finding could help halve rates of dementia, which affects 850,000 people in the UK and 36 million worldwide.
Researchers from the University of Edinburgh carried out two studies mapping the disease - one in Scotland among people born in 1921 and the other, in Swedish twins.
In Sweden, the further north people lived, the greater their risk of dementia.
Researchers found that twins living in the north were two or three times more likely to develop dementia compared with those in the south, after they accounted for factors such as age, gender, and genes.
In Scotland, the study revealed a substantial change in disease risk depending on where people lived as an adult. There was no change in risk linked to where people lived as children.

Experts say that this variation is likely to be caused by common environmental factors that affect people in adulthood - such as lack of sunlight exposure and Vitamin D, which has been linked to healthy brain function and dementia."




A common gut bacterium (Helicobacter pylori) may protect women against MS, study finds - Medical News Today

For comparison, the authors looked at the presence of H. pylori antibodies among 299 age- and sex-matched healthy individuals without MS, drawn from the Busselton Community Health Study.

The results of the analysis revealed that women who did not have MS were significantly more likely to be infected with H. pylori than women with MS, suggesting the bacterium may have a protective effect against the condition.

This association, however, was not found in men. In fact, men infected with the bacterium were more likely to have MS.

Explaining the possible reasons behind the protective effect of H. pylori found in women, the researchers say the bacterium may move the immune system into a less inflammatory state, which may reduce its sensitivity and lower the risk of autoimmune disorders like MS.

The team, however, says they are unable to explain why H. pylori did not appear to protect men against MS, and that this is something that needs to be investigated in future research.

Amyloid beta (A4) precursor protein expression in human periodontitis-affected gingival tissues.

Periodontitis involves periodontal tissue destruction and is associated with chronic inflammation and ageing. Periodontitis has recently been recognised as a risk factor for Alzheimer's disease (AD). We showed upregulation of molecules in the AD pathway including amyloid beta (A4) precursor protein (APP), a key gene in AD, interleukin-1 beta (IL-1β), and complement component 1 (q subcomponent, A chain) (C1QA) in periodontitis compared to healthy tissues. Here, we quantitatively analysed the expression levels of APP, IL-1β, and C1QA and determined the localisation of APP in gingival tissues.

DESIGN:

Fourteen chronic periodontitis patients and 14 healthy participants were enrolled. Six samples of total RNA from two distinct sites of healthy and periodontitis-affected gingival tissues from three randomly selected patients were used for microarray analyses, and significant biological pathways in periodontitis were identified. Differential gene expression of APP, IL-1β, and C1QA, which belong to the AD pathway, were analysed with quantitative reverse transcription real-time polymerase chain reaction (qRT-PCR) using samples from these 14 chronic periodontitis patients and 14 healthy controls. APP localisation was analysed with immunohistochemistry.

RESULTS:

APP, IL-1β, and C1QA mRNA levels were significantly upregulated in periodontitis-affected gingival tissues. APP was mainly localised in macrophages in gingival connective tissues underneath the epithelial layers.

CONCLUSIONS:

An association between AD and periodontitis was detected with microarray and computer-aided data mining analyses. qRT-PCR identified differential gene expression in periodontitis-affected gingival tissue that may be related to AD pathogenesis. Elevated APP, IL-1β, and C1QA transcripts and APP-expressing macrophages in periodontitis-affected gingival tissues were observed, suggesting a relationship between periodontitis and AD pathogenesis.

Fenpropathrin, a Widely Used Pesticide, Causes Dopaminergic Degeneration.

Fenpropathrin is one of the widely used pyrethroids in agriculture and household and also reported to have neurotoxic effects in rodent models. In our Parkinson's disease (PD) clinic, there was a unique patient with a history of daily exposure to fenpropathrin for 6 months prior to developing Parkinsonian symptoms progressively. Since whether fenpropathrin is related to any dopaminergic degeneration was unknown, we aimed in this study to evaluate the neurotoxic effects of fenpropathrin on the dopaminergic system and associated mechanisms in vitro and in vivo. In cultured SH-SY5Y cells, fenpropathrin caused cell death, reactive oxygen species generation, Lewy body-associated proteins aggregation, and Lewy body-like intracytoplasmic inclusions formation. In rodent animals, two different injections of fenpropathrin were used for administrations, intraperitoneal (i.p), or stereotaxical (ST). The rats exhibited lower number of pokes 60 days after first i.p injection, while the rats in ST group showed a significant upregulation of apomorphine-evoked rotations 60 days after first injection. Dcreased tyrosine hydroxylase (TH) and vesicular monoamine transporter 2 (VMAT2) immunoreactivity, while increased dopamine transporter (DAT) immunoreactivity were observed in rats of either i.p or ST group 60 days after the last exposure to fenpropathrin. However, the number of TH-positive cells in the substantia nigra was more reduced 120 days after the first i.p injection than those of 60 days. Our data demonstrated that exposure to fenpropathrin could mimic the pathologic and pathogenetic features of PD especially in late onset cases. These results imply fenpropathrin as a DA neurotoxin and a possible environmental risk factor for PD.

BPA and BPS affect embryonic brain development in zebrafish

Bisphenol A, known as BPA, is produced in massive quantities around the world for use in consumer products, including household plastics. In response to public concerns, many manufacturers have replaced BPA with a chemical called bisphenol S (BPS), which is often labeled as "BPA-free" and presumed to be safer.
In a study published Monday, Jan. 12, in the Proceedings of the National Academy of Sciences (PNAS), researchers in Deborah Kurrasch's lab at the University of Calgary have provided evidence that BPA and BPS cause alterations in brain development leading to hyperactivity in zebrafish.
Researchers discovered the number of neurons generated in the developing zebrafish brains increased by 180 per cent compared with unexposed fish. They also learned that BPS increased the number of neurons by 240 per cent in similar experiments. The result was a change in behaviour, with the fish demonstrating greater hyperactivity later in life.
Another surprise finding was that zebrafish receptors targeted by BPA and BPS to mediate this early neuronal birth in zebrafish brains were androgen receptors. Assumptions based on numerous reports postulated that BPA and BPS modulate normal physiology by mimicking the endogenous sex steroid estrogen, and not testosterone.

New project explores role of gut microbiota in preventing diet- and brain-related diseases

A new project comprising thirty organisations from fifteen countries has started working together to study the microorganisms in our intestines and the role they play in health, well-being, and how they can help prevent diet- and brain-related diseases. The project receives funding from the European Union's Seventh Framework Program and has partners from EU and non-EU countries.
Gut microbiota are the microbe populations living in our intestines, which contain trillions of microorganisms, including at least one thousand different species of bacteria. Altogether, the microbiota can weigh up to two kilograms. One third of our gut microbiota is common across most people, while two thirds are specific to each of us. In other words, the microbiota in your intestine is analogous to a personal identity card.
"Our challenge is to provide a proof of concept that dietary interventions with food and ingredients designed to modulate the gut microbiota can contribute to controlling and reducing the incidence of diet-related diseases, such as obesity, metabolic syndrome and behavioural disorders - epidemics in our developed society," said Yolanda Sanz, MyNewGut's project coordinator.
MyNewGut, officially launched in December 2013 is a five-year multidisciplinary project studying the gut microbiota, its genome (or microbiome) and their roles in human physiology. Organisations around the world have been working in this field for many years. But, this is the first time an EU-supported initiative has brought together such a unique consortium of world-leading experts from various scientific and industrial disciplines, in order to investigate the microbiome's influence on human health and disease.