Detection of Clostridium perfringens toxin genes in the gut microbiota of autistic children. - PubMed - NCBI

We studied stool specimens from 33 autistic children aged 2-9 years with gastrointestinal (GI) abnormalities and 13 control children without autism and without GI symptoms. We performed quantitative comparison of all Clostridium species and Clostridium perfringens strains from the fecal microbiota by conventional, selective anaerobic culture methods. We isolated C. perfringens strains and performed PCR analysis for the main C. perfringens toxin genes, alpha, beta, beta2, epsilon, iota and C. perfringens enterotoxin gene. Our results indicate that autistic subjects with gastrointestinal disease harbor statistically significantly (p = 0.031) higher counts of C. perfringens in their gut compared to control children. Autistic subjects also harbor statistically significantly (p = 0.015) higher counts of beta2-toxin gene-producing C. perfringens in their gut compared to control children, and the incidence of beta2-toxin gene-producing C. perfringens is significantly higher in autistic subjects compared to control children (p = 0.014). Alpha toxin gene was detected in all C. perfringens strains studied. C. perfringens enterotoxin gene was detected from three autistic and one control subject. Beta, epsilon, and iota toxin genes were not detected from autistic or control subjects."



'via Blog this'

Food additive found in candy, gum could alter digestive cell structure and function: Small intestinal cells hindered by chronic exposure to common food additive -- ScienceDaily

"The ability of small intestine cells to absorb nutrients and act as a barrier to pathogens is 'significantly decreased' after chronic exposure to nanoparticles of titanium dioxide, a common food additive found in everything from chewing gum to bread, according to new research."



'via Blog this'

Neurotoxic reactive astrocytes are induced by activated microglia :

"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'

Vitamin B3 modulates mitochondrial vulnerability and prevents glaucoma in aged mice | Science

"Glaucoma is the most common cause of age-related blindness in the United States. There is currently no cure, and once vision is lost, the condition is irreversible. Williams et al. now report that vitamin B3 (also known as niacin) prevents eye degeneration in glaucoma-prone mice (see the Perspective by Crowston and Trounce). Supplementing the diets of young mice with vitamin B3 averted early signs of glaucoma. Vitamin B3 also halted further glaucoma development in aged mice that already showed signs of the disease. Thus, healthy intake of vitamin B3 may protect eyesight."



'via Blog this'

In vitro protective efficacy of Lithium chloride against Mycoplasma hyopneumoniae infection. - PubMed - NCBI

 Mycoplasma hyopneumoniae (M. hyopneumoniae) infection affects the swine industry. Lithium chloride (LiCl), is a drug used to treat bipolar disorder and has also shown activity against bacterial and viral infections. Herein, we evaluated the antibacterial activity of LiCl on PK-15 cells infected with M. hyopneumoniae. Incubation of LiCl (40mM) with cells for 24h, did not significantly affect the cell viability. The qRT-PCR showed ~80% reduction in M. hyopneumoniae genome when LiCl added post-infection. A direct effect of LiCl on bacteria was also observed. However, treatment of cells with LiCl prior infection, does not protect against the infection. Anti-bacterial activity of LiCl was further confirmed by IFA, which demonstrated a reduction in the bacterial protein. With 40mM LiCI, the apoptotic cell death, production of nitric oxide and superoxide anion induced by M. hyopneumoniae, were prevented by ~80%, 60% and 58% respectively. Moreover, caspase-3 activity was also reduced (82%) in cells treated with 40mM LiCl. LiCl showed activity against various strains of M. hyopneumoniae examined in our study. Collectively, our data showed that LiCl inhibited the infection of M. hyopneumoniae through anti-apoptotic mechanism.

Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota : Scientific Reports

Alzheimer’s disease is the most common form of dementia in the western world, however there is no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating the intestinal microbiota in a number of brain disorders, its impact on Alzheimer’s disease is not known. To this end we sequenced bacterial 16S rRNA from fecal samples of Aβ precursor protein (APP) transgenic mouse model and found a remarkable shift in the gut microbiota as compared to non-transgenic wild-type mice. Subsequently we generated germ-free APP transgenic mice and found a drastic reduction of cerebral Aβ amyloid pathology when compared to control mice with intestinal microbiota. Importantly, colonization of germ-free APP transgenic mice with microbiota from conventionally-raised APP transgenic mice increased cerebral Aβ pathology, while colonization with microbiota from wild-type mice was less effective in increasing cerebral Aβ levels. Our results indicate a microbial involvement in the development of Abeta amyloid pathology, and suggest that microbiota may contribute to the development of neurodegenerative diseases."



'via Blog this'

Inhibitory effects of bee venom and its components against viruses in vitro and in vivo. - PubMed - NCBI

 Bee venom (BV) from honey bee (Apis Melifera L.) contains at least 18 pharmacologically active components including melittin (MLT), phospholipase A2 (PLA2), and apamin etc. BV is safe for human treatments dose dependently and proven to possess different healing properties including antibacterial and antiparasitidal properties. Nevertheless, antiviral properties of BV have not well investigated. Hence, we identified the potential antiviral properties of BV and its component against a broad panel of viruses. Co-incubation of non-cytotoxic amounts of BV and MLT, the main component of BV, significantly inhibited the replication of enveloped viruses such as Influenza A virus (PR8), Vesicular Stomatitis Virus (VSV), Respiratory Syncytial Virus (RSV), and Herpes Simplex Virus (HSV). Additionally, BV and MLT also inhibited the replication of non-enveloped viruses such as Enterovirus-71 (EV-71) and Coxsackie Virus (H3). Such antiviral properties were mainly explained by virucidal mechanism. Moreover, MLT protected mice which were challenged with lethal doses of pathogenic influenza A H1N1 viruses. Therefore, these results provides the evidence that BV and MLT could be a potential source as a promising antiviral agent, especially to develop as a broad spectrum antiviral agent.



'via Blog this'

Prenatal bisphenol A exposure weakens body's fullness cues

The new study found mice born to mothers exposed to bisphenol A were less responsive to the hormone leptin, which is sometimes called the satiety hormone. Leptin helps inhibit the appetite by reducing hunger pangs when the body does not need energy. The hormone sends signals to the hypothalamus region of the brain to suppress the appetite.
"Our findings show that bisphenol A can promote obesity in mice by altering the hypothalamic circuits in the brain that regulate feeding behavior and energy balance," said the study's senior author, Alfonso Abizaid, Ph.D., of the Department of Neuroscience at Carleton University in Ottawa, Canada. "Low level prenatal exposure to BPA delays a surge of leptin after birth that allows mice to develop the proper response to the hormone. BPA exposure permanently alters the neurobiology in the affected mice, making them prone to obesity as adults.



'via Blog this'

Does eating liquorice in pregnancy raise the risk of ADHD? - Health News - NHS Choices

Researchers found eating liquorice in pregnancy is linked to a range of developmental issues.
The news is based on Finnish research on almost 400 young adolescents with an average age of 12.5.
Liquorice consumption is thought to be higher in Finland than in the UK thanks to the popularity of salmiakki, a popular salty liquorice snack.
Researchers found girls whose mothers had consumed high amounts of liquorice during pregnancy were more likely to go through puberty at a younger age.
And girls and boys whose mothers consumed high amounts scored seven points lower on intelligence tests, and higher for attention deficit hyperactivity disorder (ADHD).
The component in liquorice thought to cause damage is called glycyrrhizin.

Kynurenine pathway metabolomics predicts and provides mechanistic insight into multiple sclerosis progression : Scientific Reports

Activation of the kynurenine pathway (KP) of tryptophan metabolism results from chronic inflammation and is known to exacerbate progression of neurodegenerative disease. To gain insights into the links between inflammation, the KP and multiple sclerosis (MS) pathogenesis, we investigated the KP metabolomics profile of MS patients. Most significantly, we found aberrant levels of two key KP metabolites, kynurenic acid (KA) and quinolinic acid (QA). The balance between these metabolites is important as it determines overall excitotoxic activity at the N-methyl-D-Aspartate (NMDA) receptor. We also identified that serum KP metabolic signatures in patients can discriminate clinical MS subtypes with high sensitivity and specificity. A C5.0 Decision Tree classification model discriminated the clinical subtypes of MS with a sensitivity of 91%. After validation in another independent cohort, sensitivity was maintained at 85%. Collectively, our studies suggest that abnormalities in the KP may be associated with the switch from early-mild stage MS to debilitating progressive forms of MS and that analysis of KP metabolites in MS patient serum may have application as MS disease biomarkers."




Fast food packaging contains potentially harmful chemicals that can leach into food

 In the most comprehensive analysis to date on the prevalence of highly fluorinated chemicals in fast food packaging in the United States, researchers tested more than 400 samples from 27 fast food chains throughout the country. The samples, consisting of paper wrappers, paperboard, and drink containers, were analyzed for a class of chemicals called PFASs (per- and polyfluoroalkyl substances), also known as PFCs. These highly fluorinated chemicals are widely used in an array of nonstick, stain-resistant, and waterproof products, including carpeting, cookware, outdoor apparel, as well as food packaging.
"These chemicals have been linked with numerous health problems, so it's concerning that people are potentially exposed to them in food," says Laurel Schaider, an environmental chemist at Silent Spring Institute and the study's lead author. Exposure to some PFASs has been associated with cancer, thyroid disease, immune suppression, low birth weight, and decreased fertility. "Children are especially at risk for health effects because their developing bodies are more vulnerable to toxic chemicals," says Schaider. Approximately one third of children in the U.S. consume fast food every day."



Translational Psychiatry - Particulate air pollutants, APOE alleles and their contributions to cognitive impairment in older women and to amyloidogenesis in experimental models

 Exposure to particulate matter (PM) in the ambient air and its interactions with APOE alleles may contribute to the acceleration of brain aging and the pathogenesis of Alzheimer’s disease (AD). Neurodegenerative effects of particulate air pollutants were examined in a US-wide cohort of older women from the Women’s Health Initiative Memory Study (WHIMS) and in experimental mouse models. Residing in places with fine PM exceeding EPA standards increased the risks for global cognitive decline and all-cause dementia respectively by 81 and 92%, with stronger adverse effects in APOE ε4/4 carriers. Female EFAD transgenic mice (5xFAD+/−/human APOE ε3 or ε4+/+) with 225 h exposure to urban nanosized PM (nPM) over 15 weeks showed increased cerebral β-amyloid by thioflavin S for fibrillary amyloid and by immunocytochemistry for Aβ deposits, both exacerbated by APOE ε4. Moreover, nPM exposure increased Aβ oligomers, caused selective atrophy of hippocampal CA1 neurites, and decreased the glutamate GluR1 subunit. Wildtype C57BL/6 female mice also showed nPM-induced CA1 atrophy and GluR1 decrease. In vitro nPM exposure of neuroblastoma cells (N2a-APP/swe) increased the pro-amyloidogenic processing of the amyloid precursor protein (APP). We suggest that airborne PM exposure promotes pathological brain aging in older women, with potentially a greater impact in ε4 carriers. The underlying mechanisms may involve increased cerebral Aβ production and selective changes in hippocampal CA1 neurons and glutamate receptor subunits.



Effects of titanium dioxide nanoparticles exposure on parkinsonism in zebrafish larvae and PC12. - PubMed - NCBI

Nanomaterials hold significant potential for industrial and biomedical application these years. Therefore, the relationship between nanoparticles and neurodegenerative disease is of enormous interest. In this contribution, zebrafish embryos and PC12 cell lines were selected for studying neurotoxicity of titanium dioxide nanoparticles (TiO2 NPs). After exposure of different concentrations of TiO2 NPs to embryos from fertilization to 96 hpf, the hatching time of zebrafish was decreased, accompanied by an increase in malformation rate. However, no significant increases in mortality relative to control were observed. These results indicated that TiO2 NPs exposure hold a risk for premature of zebrafish embryos, but not fatal. The further investigation confirmed that TiO2 NPs could accumulate in the brain of zebrafish larvae, resulting in reactive oxygen species (ROS) generation and cell death of hypothalamus. Meanwhile, q-PCR analysis showed that TiO2 NPs exposure increased the pink1, parkin, α-syn and uchl1 gene expression, which are related with the formation of Lewy bodies. We also observed loss of dopaminergic neurons in zebrafish and in vitro. These remarkable hallmarks are all linked to these Parkinson's disease (PD) symptoms. Our results indicate that TiO2NPs exposure induces neurotoxicity in vivo and in vitro, which poses a significant risk factor for the development of PD.




Edible and Medicinal Mushrooms: Emerging Brain Food for the Mitigation of Neurodegenerative Diseases

There is an exponential increase in dementia in old age at a global level because of increasing life expectancy. The prevalence of neurodegenerative diseases such as dementia and Alzheimer's disease (AD) will continue to rise steadily, and is expected to reach 42 million cases worldwide in 2020. Despite the advancement of medication, the management of these diseases remains largely ineffective. Therefore, it is vital to explore novel nature-based nutraceuticals to mitigate AD and other age-related neurodegenerative disorders. Mushrooms and their extracts appear to hold many health benefits, including immune-modulating effects. A number of edible mushrooms have been shown to contain rare and exotic compounds that exhibit positive effects on brain cells both in vitro and in vivo. In this review, we summarize the scientific information on edible and culinary mushrooms with regard to their antidementia/AD active compounds and/or pharmacological test results. The bioactive components in these mushrooms and the underlying mechanism of their activities are discussed. In short, these mushrooms may be regarded as functional foods for the mitigation of neurodegenerative diseases.



'via Blog this'

ASU gut microbe study shows promise as a potential treatment for autism | EurekAlert! Science News

"The key to fighting autism might lie not in the mind, but in the gut.

A team led by Arizona State University researchers is taking a novel approach the search for effective autism treatments by focusing on improving the gut microbiome through fecal microbial transplants.

Early results are promising, but additional testing is required before an FDA-approved therapy would be available or recommended to the public.

The team -- including collaborators from Northern Arizona University, Ohio State University and the University of Minnesota -- completed a study involving 18 participants with autism spectrum disorders who ranged in age from 7 to 16 years old. The results were recently published in the journal Microbiome.

Participants underwent a 10-week treatment program involving antibiotics, a bowel cleanse and daily fecal microbial transplants over eight weeks.

Past ASU research has shown ties between autism symptoms and the composition and diversity of a person's gut microbes.

The treatment program showed long-term benefits, including an average 80 percent improvement of gastrointestinal symptoms associated with autism spectrum disorders and 20-25 percent improvement in autism behaviors, including improved social skills and better sleep habits."



'via Blog this'

TLR3 downregulates expression of schizophrenia gene Disc1 via MYD88 to control neuronal morphology. - PubMed - NCBI

Viral infection during fetal or neonatal stages increases the risk of developing neuropsychiatric disorders such as schizophrenia and autism spectrum disorders. Although neurons express several key regulators of innate immunity, the role of neuronal innate immunity in psychiatric disorders is still unclear. Using cultured neurons and in vivo mouse brain studies, we show here that Toll-like receptor 3 (TLR3) acts through myeloid differentiation primary response gene 88 (MYD88) to negatively control Disrupted in schizophrenia 1 (Disc1) expression, resulting in impairment of neuronal development. Cytokines are not involved in TLR3-mediated inhibition of dendrite outgrowth. Instead, TLR3 signaling suppresses expression of several psychiatric disorder-related genes, including Disc1 The impaired dendritic arborization caused by TLR3 activation is rescued by MYD88 deficiency or DISC1 overexpression. In addition, TLR3 activation at the neonatal stage increases dendritic spine density, but narrows spine heads at postnatal day 21 (P21), suggesting a long-lasting effect of TLR3 activation on spinogenesis. Our study reveals a novel mechanism of TLR3 in regulation of dendritic morphology and provides an explanation for how environmental factors influence mental health.



'via Blog this'

Cholesterol—Good for the brain, bad for the heart

 Healthy brains need plenty of cholesterol for nerve cells to grow and work properly, but diabetes can reduce the amount of cholesterol in the brain, as a Joslin Diabetes Center team has demonstrated. Joslin researchers and their colleagues now have gone on to show that mice that are genetically modified to suppress cholesterol production in the brain show dramatic symptoms of neurological impairment . This finding may help to explain why the risk of developing Alzheimer's disease increases in diabetes, says Heather Ferris, M.D., Ph.D., a Joslin research associate and lead author on a paper about the work published in PNAS


Loss of astrocyte cholesterol synthesis disrupts neuronal function and alters whole-body metabolism PNAS


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."