Autism and neuro-immune-gut link

Recent evidences sustain the hypothesis that host-bacteria interactions play a critical role in regulating tissue and body homeostasis. Gut microbiota and the brain are strongly interconnected and share communication pathways. Modifications in gut bacteria compositions are correlated to changes in behaviors. Indeed, autism spectrum disorders (ASD) are linked to dysfunctions of the gut bacteria-brain axis. Possible therapeutic strategies in ASD management will aim to restore dysbiosis and gut bacteria imbalance

Inflammation and Neuro-Immune Dysregulations in Autism Spectrum Disorders

Autism Spectrum Disorder (ASD) is characterized by persistent deficits in social communication and interaction and restricted-repetitive patterns of behavior, interests, or activities. Strong inflammation states are associated with ASD. This inflammatory condition is often linked to immune system dysfunction. Several cell types are enrolled to trigger and sustain these processes. Neuro-inflammation and neuro-immune abnormalities have now been established in ASD as key factors in its development and maintenance. In this review, we will explore inflammatory conditions, dysfunctions in neuro-immune cross-talk, and immune system treatments in ASD management

Stem Cell-Derived Exosomes in Autism Spectrum Disorder

Neurodevelopmental lifelong pathologies defined by problems with social interaction, communication capacity and presence of repetitive/stereotyped clusters of behavior and interests are grouped under the definition of autism spectrum disorder (ASD). ASD prevalence is still increasing, indicating the need to identify specific biomarkers and novel pharmacotherapies. Neuroinflammation and neuro-immune cross-talk dysregulation are specific hallmarks of ASD, offering the possibility of treating these disorders by stem cell therapy. Indeed, cellular strategies have been postulated, proposed and applied to ASD. However, less is known about the molecular action mechanisms of stem cells. As a possibility, the positive and restorative effects mediated by stem cells could be due to their paracrine activity, by which stem cells produce and release several ameliorative and anti-inflammatory molecules. Among the secreted complex tools, exosomes are sub-organelles, enriched by RNA and proteins, that provide cell-to-cell communication. Exosomes could be the mediators of many stem cell-associated therapeutic activities. This review article describes the potential role of exosomes in alleviating ASD symptoms

Optimization of Peripheral Blood Mononuclear Cell Extraction from Small Volume of Blood Samples: Potential Implications for Children-Related Diseases

Managing medical procedures for children with problematic disorders is a challenging approach, especially in the case of blood withdrawal for autism spectrum disorder-affected children. Peripheral blood mononuclear cells (PBMC) represent an important cellular model to study immune responses and drug toxicity. The monocytic cells, a fraction of PBMC, are strongly involved in some pathophysiological processes, such as inflammation and immune system changes. Here, we propose a simple, reliable protocol for obtaining peripheral blood-derived mononuclear cells from small volumes of blood samples

Stem cell therapy in autism: recent insights

Autism spectrum disorders (ASDs) are characterized by core domains: persistent deficits in social communication and interaction; restricted, repetitive patterns of behavior, interests, or activities. ASDs comprise heterogeneous and complex neurodevelopmental pathologies with well-defined inflammatory conditions and immune system dysfunction. Due to neurobiologic changes underlying ASD development, cell-based therapies have been proposed and applied to ASDs. Indeed, stem cells show specific immunologic properties, which make them promising candidates in ASD treatment. This comprehensive up-to-date review focuses on ASD cellular/molecular abnormalities, potentially useful stem cell types, animal models, and current clinical trials on the use of stem cells in treating autism. Limitations are also discussed

Speech-Stimulating Substances in Autism Spectrum Disorders

Autism spectrum disorder (ASD) is characterized by the core domains of persistent deficits in social communication and restricted-repetitive patterns of behaviors, interests, or activities. A heterogeneous and complex set of neurodevelopmental conditions are grouped in the spectrum. Pro-inflammatory events and immune system dysfunctions are cellular and molecular events associated with ASD. Several conditions co-occur with ASD: seizures, gastro-intestinal problems, attention deficit, anxiety and depression, and sleep problems. However, language and speech issues are key components of ASD symptoms current therapies find difficult to face. Several speech-stimulating substances have been shown to be effective in increasing speech ability in ASD subjects. The need for large clinical trials to determine safety and efficacy is recommended

Intraperitoneal administration of oxygen/ozone to rats reduces the pancreatic damage induced by streptozotocin

Background: The rat model of streptozotocin (STZ)-induced pancreatic damage was used to examine whether a systemic oxygen/ozone mixture could be beneficial for the pancreas by reducing the machinery of the local detrimental mediators released by STZ. Results: The results showed that oxygen/ozone administration (150 μg/Kg i.p.) for ten days in STZ rats increased the endogenous glutathione-s-transferase (GST) enzyme and nuclear factor-erythroid 2-related factor 2 (Nrf2) into the pancreatic tissue, together with reduction of 4-hydroxynonenal (4-HNE) and PARP-1 compared to STZ rats receiving O2only. Interestingly, these changes resulted in higher levels of serum insulin and leptin, and pancreatic glucagon immunostaining. Consequently, glucose metabolism improved as evidenced by the monitoring of glycemia throughout. Conclusions: This study provides evidence that systemic administration of oxygen/ozone reduces the machinery of detrimental mediators released by STZ into the pancreas with less local damage and better functionality

PSEN1 Compound Heterozygous Mutations Associated with Cerebral Amyloid Angiopathy and Cognitive Decline Phenotype

Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder caused by the deposition of amyloid beta‐peptide (Aβ) aggregates. Aβ aggregates lead to vessel rupture and intracerebral hemorrhages, detected by magnetic resonance imaging (MRI). Presenile CAA is usually genetically determined by mutations in the amyloid precursor protein (APP) gene. However, mutations after codon 200 in the presenilin 1 (PSEN1) gene have been reported to facilitate CAA onset. Here, we analyzed the genetic bases in a patient of 55 years old affected by CAA and cognitive decline. DNA was isolated and genetic analysis was performed by Next‐Generation Sequencing (NGS). RNA was extracted and retro‐transcribed to perform segregation analysis by TOPO‐TA cloning. WB analysis was carried out to check the impact of the mutations on protein. Two compound heterozygous mutations in PSEN1 exon 10, such as a novel stop‐gain mutation (c.1070C > G) and a pathogenic splice variant (c.1129A > T), were found by NGS. Both mutations altered the presenilin 1 protein, truncating its C‐terminal portion. This is the first case of CAA and cognitive decline caused by two compound mutations in PSEN1. With this report, we suggest extending the genetic analysis to PSEN1 when cerebral microbleeds are observed by MRI investigation in a patient affected by presenile cognitive decline

Inhibition of aldose-reductase-2 by a benzofuroxane derivative bf-5m increases the expression of kcne1, kcnq1 in high glucose cultured H9c2 cardiac cells and sudden cardiac death

Long QT syndrome (LQTS) is characterized by prolonged QT interval, leading to sudden cardiac death. Hyperglycemia is an important risk factor for LQTS, inhibiting the cardiac rapid component delayed rectifier K+ current (Iks), responsible for QT interval. We previously showed that the new ALR2 inhibitor BF-5m supplies cardioprotection from QT prolongation induced by high glucose concentration in the medium, reducing QT interval prolongation and preserving morphology. Here we investigated the effects of BF-5m on cell cytotoxicity and viability in H9c2 cells, and on cellular potassium ion channels expression. H9c2 cells were grown in medium with high glucose and high glucose plus the BF-5m by assessing the cytotoxic effects and the cell survival rate. In addition, KCNE1 and KCNQ1 expression in plasma and mitochondrial membranes were monitored. Also, the expression levels of miR-1 proved to suppress KCNQ1 and KCNE1, were analyzed. BF-5m treatment reduced the cytotoxic effects of high glucose on H9c2 cells by increasing cell survival rate and improving H9c2 morphology. Plasmatic KCNE1 and KCNQ1 expression levels were restored by BF-5m in H9c2 exposed to high glucose, down-regulating miR-1. These results suggest that BF-5m exerts cardioprotection from high glucose in rat heart ventricle H9c2 cells exposed to high glucose