Statins a new hope for treatment of Multiple Sclerosis an autoimmune disease - ShoutasScience

University college of London (UCL) researchers in the initial phase of clinical trial have found out that taking high doses of Statins (Simvastatin), a cholesterol-lowering drug by the people with the secondary progressive form of multiple sclerosis (MS) had a significant reduction in the rate of brain atrophy (brain shrinkage) over two years and also had better disability scores at the end of study. The phase 2 Clinical trial was conducted in collaboration with National Institute for Health Research (NIHR), the MS Society (UK), the National MS Society (US), the NHS and UK universities."




Can Omega-3 Help Prevent Alzheimer’s Disease? Brain SPECT Imaging Shows Possible Link | Journal of Alzheimer's Disease

 Amsterdam, NL – The incidence of Alzheimer’s disease (AD) is expected to triple in the coming decades and no cure has been found. Recently, interest in dietary approaches for prevention of cognitive decline has increased. In particular, the omega-3 fatty acids have shown anti-amyloid, anti-tau and anti-inflammatory actions in the brains of animals. In a new article published in the Journal of Alzheimer’s Disease, researchers have found that for patients with high omega-3 levels, blood flow in specific areas of the brain is increased."



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CX3CR1+ monocytes modulate learning and learning-dependent dendritic spine remodeling via TNF-[alpha] : Nature Medicine : Nature Research

Impaired learning and cognitive function often occurs during systemic infection or inflammation. Although activation of the innate immune system has been linked to the behavioral and cognitive effects that are associated with infection, the underlying mechanisms remain poorly understood. Here we mimicked viral immune activation with poly(I:C), a synthetic analog of double-stranded RNA, and longitudinally imaged postsynaptic dendritic spines of layer V pyramidal neurons in the mouse primary motor cortex using two-photon microscopy. We found that peripheral immune activation caused dendritic spine loss, impairments in learning-dependent dendritic spine formation and deficits in multiple learning tasks in mice. These observed synaptic alterations in the cortex were mediated by peripheral-monocyte-derived cells and did not require microglial function in the central nervous system. Furthermore, activation of CX3CR1highLy6Clow monocytes impaired motor learning and learning-related dendritic spine plasticity through tumor necrosis factor (TNF)-α-dependent mechanisms. Taken together, our results highlight CX3CR1high monocytes and TNF-α as potential therapeutic targets for preventing infection-induced cognitive dysfunction.

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Lithium May Prevent Neuron Damage In traumatic brain injury Patients - Neuroscience News

According to researchers, lithium, a drug commonly used to treat bipolar disorder, and rapamycin can help to protect neurons from further damage in those with TBI.

Source: Rutgers.

A drug used to treat bipolar disorder and other forms of depression may help to preserve brain function and prevent nerve cells from dying in people with a traumatic brain injury, according to a new Rutgers University study.

In research published in Scientific Reports, Rutgers scientists discovered that lithium – used as a mood stabilizer and to treat depression and bipolar disorder – and rapamycin, a treatment for some forms of cancer, protected nerve cells in the brain and stopped the chemical glutamate from sending signals to other cells and creating further brain cell damage."



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Endothelial TLR4 and the microbiome drive cerebral cavernous malformations : Nature : Nature Research

Cerebral cavernous malformations (CCMs) are a cause of stroke and seizure for which no effective medical therapies yet exist. CCMs arise from the loss of an adaptor complex that negatively regulates MEKK3–KLF2/4 signalling in brain endothelial cells, but upstream activators of this disease pathway have yet to be identified. Here we identify endothelial Toll-like receptor 4 (TLR4) and the gut microbiome as critical stimulants of CCM formation. Activation of TLR4 by Gram-negative bacteria or lipopolysaccharide accelerates CCM formation, and genetic or pharmacologic blockade of TLR4 signalling prevents CCM formation in mice. Polymorphisms that increase expression of the TLR4 gene or the gene encoding its co-receptor CD14 are associated with higher CCM lesion burden in humans. Germ-free mice are protected from CCM formation, and a single course of antibiotics permanently alters CCM susceptibility in mice. These studies identify unexpected roles for the microbiome and innate immune signalling in the pathogenesis of a cerebrovascular disease, as well as strategies for its treatment."



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A chronic low dose of [Delta]9-tetrahydrocannabinol (THC) restores cognitive function in old mice : Nature Medicine : Nature Research

Cannabis sativa plant
Cannabis sativa plant (Photo credit: Wikipedia)
The balance between detrimental, pro-aging, often stochastic processes and counteracting homeostatic mechanisms largely determines the progression of aging. There is substantial evidence suggesting that the endocannabinoid system (ECS) is part of the latter system because it modulates the physiological processes underlying aging1, 2. The activity of the ECS declines during aging, as CB1 receptor expression and coupling to G proteins are reduced in the brain tissues of older animals3, 4, 5 and the levels of the major endocannabinoid 2-arachidonoylglycerol (2-AG) are lower6. However, a direct link between endocannabinoid tone and aging symptoms has not been demonstrated. Here we show that a low dose of Δ9-tetrahydrocannabinol (THC) reversed the age-related decline in cognitive performance of mice aged 12 and 18 months. This behavioral effect was accompanied by enhanced expression of synaptic marker proteins and increased hippocampal spine density. THC treatment restored hippocampal gene transcription patterns such that the expression profiles of THC-treated mice aged 12 months closely resembled those of THC-free animals aged 2 months. The transcriptional effects of THC were critically dependent on glutamatergic CB1 receptors and histone acetylation, as their inhibition blocked the beneficial effects of THC. Thus, restoration of CB1 signaling in old individuals could be an effective strategy to treat age-related cognitive impairments."



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Fetal Exposure to Antidepressants May Alter Corpus Callosum Microstructure

 Selective serotonin reuptake inhibitors (SSRIs) may affecting white-matter brain development and alter the development of the fetal corpus callosum, according to results of a prospective study presented at the 2017 Annual Meeting of the Pediatric Academic Societies/American Society of Pediatric Nephrology (PAS/ASPN).



Erythritol is a pentose-phosphate pathway metabolite and associated with adiposity gain in young adults

 "The prevention of weight gain in adulthood is a public health challenge, particularly given the difficulty of losing weight. Data on freshmen were collected at the beginning and end of the academic year, and baseline blood samples were studied to find markers of incident weight gain. A metabolite, erythritol, was elevated at the beginning of the year in freshmen who went on to gain weight, fat, and abdominal fat compared with freshmen with stable weight. Erythritol is a sugar substitute low-calorie sweetener, and prior studies claimed no endogenous synthesis. We report a previously unrecognized metabolism of glucose to erythritol, and given the association between erythritol and weight gain, research is needed to understand whether and how this pathway contributes to weight gain risk."



Aerial spraying to combat mosquitos linked to increased risk of autism in children

 Researchers who will present the abstract, "Aerial Pesticide Exposure Increases the Risk of Developmental Delay and Autism Spectrum Disorder," identified a swampy region in central New York where health officials use airplanes to spray pyrethroid pesticides each summer. The pesticides target mosquitos that carry the eastern equine encephalitis virus, which can cause swelling of the brain and spinal cord. They found that children living in ZIP codes in which aerial pesticide spraying has taken place each summer since 2003 were approximately 25 percent more likely to have an autism diagnosis or documented developmental delay compared to those in ZIP codes with other methods of pesticide distribution, such as manually spreading granules or using hoses or controlled droplet applicators."



Preliminary study suggests possible new treatment for MS related to the Epstein-Barr virus -- ScienceDaily

The study investigates the relationship between multiple sclerosis and the Epstein-Barr virus (EBV), a herpes virus that is extremely common but causes no symptoms in most people. However, when a person contracts the virus as a teenager or adult, it often leads to mononucleosis. Previous research has shown a link between the virus and MS.

For the study, researchers removed the participants' own T cells and stimulated them to boost their ability to recognize and destroy cells infected with Epstein-Barr virus. They then injected participants with infusions of escalating doses of T cells every two weeks for six weeks. They followed the patients through 26 weeks to look for evidence of side effects and possible improvement of symptoms.
Three of the participants showed improvement, starting two to eight weeks after the first infusion.
"One person with secondary progressive MS showed striking improvement," Pender said. "This participant had a significant increase in ambulation from 100 yards with a walker at the start of the study, and over the previous five years, to three quarters of a mile, and was now also able to walk shorter distances with only one sided assistance. Lower leg spasms that had persisted for 20 years resolved."


CRISPR Eliminates HIV in Live Animals | GEN

 Due to their innate nature to hide away and remain latent for extended periods of time, HIV infections have proven notoriously difficult to eliminate. Yet now, new data released from a research team led by investigators at the Lewis Katz School of Medicine at Temple University (LKSOM) and the University of Pittsburgh shows that HIV DNA can be excised from the genomes of living animals to eliminate further infection. Additionally, the researchers are the first to perform this feat in three different animal models, including a "humanized" model in which mice were transplanted with human immune cells and infected with the virus. Findings from the new study were published recently in Molecular Therapy in an article entitled “In Vivo Excision of HIV-1 Provirus by saCas9 and Multiplex Single-Guide RNAs in Animal Models.”      published in Molecular therapy



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Cellular cholesterol facilitates the post-entry replication cycle of herpes simplex virus 1. - PubMed - NCBI

 Cholesterol is an essential component of cell membranes and is required for HSV-1 entry (1-3). Treatment of HSV-1-infected Vero cells with methyl beta-cyclodextrin from 2 - 9 hours post-entry reduced plaque numbers. Transport of incoming viral capsids to the nuclear periphery was unaffected by cholesterol reduction suggesting that cell cholesterol is important for the HSV-1 replicative cycle at a stage(s) beyond entry after the arrival of capsids at the nucleus. The synthesis and release of infectious HSV-1 and cell-to-cell spread of infection were all impaired in cholesterol-reduced cells. Propagation of HSV-1 on DHCR24-/- fibroblasts, which lack the desmosterol-to-cholesterol conversion enzyme, resulted in the generation of infectious, extracellular virions (HSVdes) that lack cholesterol and likely contain desmosterol. The specific infectivity (PFU per viral genome) of HSVchol and HSVdes were similar suggesting cholesterol or desmosterol in the HSV envelope support similar levels of infectivity. However, infected DHCR24-/- fibroblasts released ∼1 log less infectious HSVdes and ∼1.5 logs fewer particles compared to release of cholesterol-containing particles (HSVchol) from parental fibroblasts, suggesting that the hydrocarbon tail of cholesterol facilitates viral synthesis. Together, the results suggest multiple roles for cholesterol in the HSV-1 replicative cycle.Importance HSV-1 infections are associated with a wide range of clinical manifestations that are of public health importance. Cholesterol is a key player in the complex interaction between viral and cellular factors that allows HSV-1 to enter host cells and establish infection. Previous reports have demonstrated a role for cellular cholesterol in the entry of HSV-1 into target cells. Here, we employ both chemical treatment and cells that are genetically defined to synthesize only desmosterol to demonstrate that cholesterol is important at stages following the initial entry and transport of viral capsids to the nucleus. Viral protein expression, encapsidation of viral genome and the release of mature virions were impacted by the reduction of cellular cholesterol. Cholesterol was also critical for cell-to-cell spread of infection. These findings provide new insights into the cholesterol-dependence of HSV-1 replication.



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Could Parkinson's disease start in the gut? -- ScienceDaily

 Parkinson's disease may start in the gut and spread to the brain via the vagus nerve, according to a study published in the April 26, 2017, online issue of Neurology®, the medical journal of the American Academy of Neurology. The vagus nerve extends from the brainstem to the abdomen and controls unconscious body processes like heart rate and food digestion.

Here's the paper:

Vagotomy and Parkinson disease


A Swedish register–based matched-cohort study




Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome | Microbiome

 "Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, commonly accompanied by cognitive dysfunction, sleeping disturbances, orthostatic intolerance, fever, lymphadenopathy, and irritable bowel syndrome (IBS). The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. We pursued rigorous clinical characterization, fecal bacterial metagenomics, and plasma immune molecule analyses in 50 ME/CFS patients and 50 healthy controls frequency-matched for age, sex, race/ethnicity, geographic site, and season of sampling.

Results
Topological analysis revealed associations between IBS co-morbidity, body mass index, fecal bacterial composition, and bacterial metabolic pathways but not plasma immune molecules. IBS co-morbidity was the strongest driving factor in the separation of topological networks based on bacterial profiles and metabolic pathways. Predictive selection models based on bacterial profiles supported findings from topological analyses indicating that ME/CFS subgroups, defined by IBS status, could be distinguished from control subjects with high predictive accuracy. Bacterial taxa predictive of ME/CFS patients with IBS were distinct from taxa associated with ME/CFS patients without IBS. Increased abundance of unclassified Alistipes and decreased Faecalibacterium emerged as the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroides abundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS. Despite findings of differences in bacterial taxa and metabolic pathways defining ME/CFS subgroups, decreased metabolic pathways associated with unsaturated fatty acid biosynthesis and increased atrazine degradation pathways were independent of IBS co-morbidity. Increased vitamin B6 biosynthesis/salvage and pyrimidine ribonucleoside degradation were the top metabolic pathways in ME/CFS without IBS as well as in the total ME/CFS cohort. In ME/CFS subgroups, symptom severity measures including pain, fatigue, and reduced motivation were correlated with the abundance of distinct bacterial taxa and metabolic pathways.

Conclusions
Independent of IBS, ME/CFS is associated with dysbiosis and distinct bacterial metabolic disturbances that may influence disease severity. However, our findings indicate that dysbiotic features that are uniquely ME/CFS-associated may be masked by disturbances arising from the high prevalence of IBS co-morbidity in ME/CFS. These insights may enable more accurate diagnosis and lead to insights that inform the development of specific therapeutic strategies in ME/CFS subgroups."



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Sugary beverage intake and preclinical Alzheimer's disease in the community. - PubMed - NCBI

INTRODUCTION:

Excess sugar consumption has been linked with Alzheimer's disease (AD) pathology in animal models.

METHODS:

We examined the cross-sectional association of sugary beverage consumption with neuropsychological (N = 4276) and magnetic resonance imaging (N = 3846) markers of preclinical Alzheimer's disease and vascular brain injury (VBI) in the community-based Framingham Heart Study. Intake of sugary beverages was estimated using a food frequency questionnaire.

RESULTS:

Relative to consuming less than one sugary beverage per day, higher intake of sugary beverages was associated with lower total brain volume (1-2/day, β ± standard error [SE] = -0.55 ± 0.14 mean percent difference, P = .0002; >2/day, β ± SE = -0.68 ± 0.18, P < .0001), and poorer performance on tests of episodic memory (all P < .01). Daily fruit juice intake was associated with lower total brain volume, hippocampal volume, and poorer episodic memory (all P < .05). Sugary beverage intake was not associated with VBI in a consistent manner across outcomes.

DISCUSSION:

Higher intake of sugary beverages was associated cross-sectionally with markers of preclinical AD.

Sugar- and Artificially Sweetened Beverages and the Risks of Incident Stroke and Dementia | Stroke

"Background and Purpose—Sugar- and artificially-sweetened beverage intake have been linked to cardiometabolic risk factors, which increase the risk of cerebrovascular disease and dementia. We examined whether sugar- or artificially sweetened beverage consumption was associated with the prospective risks of incident stroke or dementia in the community-based Framingham Heart Study Offspring cohort.

 Methods—We studied 2888 participants aged >45 years for incident stroke (mean age 62 [SD, 9] years; 45% men) and 1484 participants aged >60 years for incident dementia (mean age 69 [SD, 6] years; 46% men). Beverage intake was quantified using a food-frequency questionnaire at cohort examinations 5 (1991–1995), 6 (1995–1998), and 7 (1998–2001). We quantified recent consumption at examination 7 and cumulative consumption by averaging across examinations. Surveillance for incident events commenced at examination 7 and continued for 10 years. We observed 97 cases of incident stroke (82 ischemic) and 81 cases of incident dementia (63 consistent with Alzheimer’s disease)



Results
—After adjustments for age, sex, education (for analysis of dementia), caloric intake, diet quality, physical activity, and smoking, higher recent and higher cumulative intake of artificially sweetened soft drinks were associated with an increased risk of ischemic stroke, all-cause dementia, and Alzheimer’s disease dementia. When comparing daily cumulative intake to 0 per week (reference), the hazard ratios were 2.96 (95% confidence interval, 1.26–6.97) for ischemic stroke and 2.89 (95% confidence interval, 1.18–7.07) for Alzheimer’s disease. Sugar-sweetened beverages were not associated with stroke or dementia.

 Conclusions—Artificially sweetened soft drink consumption was associated with a higher risk of stroke and dementia."



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Stroke and dementia risk linked to artificial sweeteners, study suggests | Society | The Guardian

Consuming a can a day of low- or no-sugar soft drink is associated with a much higher risk of having a stroke or developing dementia, researchers claim.

Their findings have prompted renewed questions about whether drinks flavoured with artificial sweeteners can increase the risk of serious illness, as heavily sugared drinks have already been shown to do.

“Drinking at least one artificially sweetened beverage daily was associated with almost three times the risk of developing stroke or dementia compared to those who drank artificially sweetened beverages less than once a week,” according to the American researchers who carried out a study published in Stroke, the journal of the American Heart Association."


Here's the paper :-

Sugar- and Artificially Sweetened Beverages and the Risks of Incident Stroke and Dementia


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Repurposed drugs targeting eIF2α-P-mediated translational repression prevent neurodegeneration in mice | Brain | Oxford Academic

 Signalling through the PERK/eIF2α-P branch of the unfolded protein response plays a critical role in controlling protein synthesis rates in cells. This pathway is overactivated in brains of patients with Alzheimer’s disease and related disorders and has recently emerged as a promising therapeutic target for these currently untreatable conditions. Thus, in mouse models of neurodegenerative disease, prolonged overactivation of PERK/eIF2α-P signalling causes sustained attenuation of protein synthesis, leading to memory impairment and neuronal loss. Re-establishing translation rates by inhibition of eIF2α-P activity, genetically or pharmacologically, restores memory and prevents neurodegeneration and extends survival. However, the experimental compounds used preclinically are unsuitable for use in humans, due to associated toxicity or poor pharmacokinetic properties. To discover compounds that have anti-eIF2α-P activity suitable for clinical use, we performed phenotypic screens on a NINDS small molecule library of 1040 drugs. We identified two compounds, trazodone hydrochloride and dibenzoylmethane, which reversed eIF2α-P-mediated translational attenuation in vitro and in vivo. Both drugs were markedly neuroprotective in two mouse models of neurodegeneration, using clinically relevant doses over a prolonged period of time, without systemic toxicity. Thus, in prion-diseased mice, both trazodone and dibenzoylmethane treatment restored memory deficits, abrogated development of neurological signs, prevented neurodegeneration and significantly prolonged survival. In tauopathy-frontotemporal dementia mice, both drugs were neuroprotective, rescued memory deficits and reduced hippocampal atrophy. Further, trazodone reduced p-tau burden. These compounds therefore represent potential new disease-modifying treatments for dementia. Trazodone in particular, a licensed drug, should now be tested in clinical trials in patients.



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Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease | Science

 Viral infections have been proposed to elicit pathological processes leading to the initiation of T helper 1 (TH1) immunity against dietary gluten and celiac disease (CeD). To test this hypothesis and gain insights into mechanisms underlying virus-induced loss of tolerance to dietary antigens, we developed a viral infection model that makes use of two reovirus strains that infect the intestine but differ in their immunopathological outcomes. Reovirus is an a virulent pathogen that elicits protective immunity, but we discovered that it can nonetheless disrupt intestinal immune homeostasis at inductive and effector sites of oral tolerance by suppressing peripheral regulatory T cell (pTreg) conversion and promoting TH1 immunity to dietary antigen. Initiation of TH1 immunity to dietary antigen was dependent on interferon regulatory factor 1 and dissociated from suppression of pTreg conversion, which was mediated by type-1 interferon. Last, our study in humans supports a role for infection with reovirus, a seemingly innocuous virus, in triggering the development of CeD."



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Identification of Fungal Species in Brain Tissue from Alzheimer's Disease by Next-Generation Sequencing. - PubMed - NCBI

 The possibility that patients diagnosed with Alzheimer's disease (AD) have disseminated fungal infection has been recently advanced by the demonstration of fungal proteins and DNA in nervous tissue from AD patients. In the present study, next-generation sequencing (NGS) was used to identify fungal species present in the central nervous system (CNS) of AD patients. Initially, DNA was extracted from frozen tissue from four different CNS regions of one AD patient and the fungi in each region were identified by NGS. Notably, whereas a great variety of species were identified using the Illumina platform, Botrytis cinerea and Cryptococcus curvatus were common to all four CNS regions analyzed. Further analysis of entorhinal/cortex hippocampus samples from an additional eight AD patients revealed a variety of fungal species, although some were more prominent than others. Five genera were common to all nine patients: Alternaria, Botrytis, Candida, Cladosporium, and Malassezia. These observations could be used to guide targeted antifungal therapy for AD patients. Moreover, the differences found between the fungal species in each patient may constitute a basis to understand the evolution and severity of clinical symptoms in AD.



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