Is Taurine a Biomarker in Autistic Spectrum Disorder?

Taurine is a sulfur-containing amino acid which is not incorporated into protein. However, taurine has various critical physiological functions including development of the eye and brain, reproduction, osmoregulation, and immune functions including anti-inflammatory as well as anti-oxidant activity. The causes of autistic spectrum disorder (ASD) are not clear but a high heritability implicates an important role for genetic factors.

Adult hippocampal neurogenesis is impaired by transient and moderate developmental thyroid hormone disruption.

The hippocampus maintains a capacity for neurogenesis throughout life, a capacity that is reduced in models of adult onset hypothyroidism. The effects of developmental thyroid hormone (TH) insufficiency on neurogenesis in the adult hippocampus, however, has not been examined. Graded degrees of TH insufficiency were induced in pregnant rat dams by administration of 0, 3 or 10ppm of 6-propylthiouracil (PTU) in drinking water from gestational day (GD) 6 until weaning.

Neuroanatomical characterization of the cellular and axonal architecture of subcortical band heterotopia in the BXD29-Tlr4/J mouse cortex.

Subcortical band heterotopia (SBH) are malformations of the human cerebral cortex typically associated with epilepsy and cognitive delay/disability. Rodent models of SBH have demonstrated strong face validity as they are accompanied by both cognitive deficits and spontaneous seizures or reduced seizure threshold. BXD29-Tlr4/J recombinant inbred mice display striking bilateral SBH, partial callosal agenesis, morphological changes in subcortical structures of the auditory pathway, and display sensory deficits in behavioral tests (Rosen et al.

PRKX, a Novel cAMP-Dependent Protein Kinase Member, Plays an Important Role in Development.

The human protein kinase X gene (PRKX) and cAMP-dependent protein kinase (PKA) are both c-AMP-dependent serine/threonine protein kinases within the protein kinase AGC subgroup. Of all the protein kinases in this group, PRKX is the least studied. PRKX has been isolated from patients with chondrodysplasia punctate and is involved in numerous processes, including sexual differentiation and fertilization, normal kidney development and autosomal dominant polycystic kidney disease (ADPKD), blood maturation, neural development, and angiogenesis in vitro.

The role of the GABA system in amphetamine-type stimulant use disorders.

Abuse of amphetamine-type stimulants (ATS) has become a global public health problem. ATS causes severe neurotoxicity, which could lead to addiction and could induce psychotic disorders or cognitive dysfunctions. However, until now, there has been a lack of effective medicines for treating ATS-related problems.

Inflammatory cytokines: potential biomarkers of immunologic dysfunction in autism spectrum disorders.

Autism is a disorder of neurobiological origin characterized by problems in communication and social skills and repetitive behavior. After more than six decades of research, the etiology of autism remains unknown, and no biomarkers have been proven to be characteristic of autism. A number of studies have shown that the cytokine levels in the blood, brain, and cerebrospinal fluid (CSF) of autistic subjects differ from that of healthy individuals; for example, a series of studies suggests that interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) are significantly elevated in different tissues in autistic subjects.

The apoptotic perspective of autism.

Autism is a severe neurodevelopmental disorder characterized by impairments in social interaction, deficits in verbal and non-verbal communication, and repetitive behavior and restricted interests. The normal brain development during fetal brain development and the first year of life is critical to the behaviors and cognitions in adulthood. Programmed cell death (apoptosis) is an important mechanism that determines the size and shape of the brain and regulates the proper wiring of developing neuronal networks.

Alteration of astrocytes and Wnt/β-catenin signaling in the frontal cortex of autistic subjects.

Background: Autism is a neurodevelopmental disorder characterized by impairments in social interaction, verbal communication and repetitive behaviors. To date the etiology of this disorder is poorly understood. Studies suggest that astrocytes play critical roles in neural plasticity by detecting neuronal activity and modulating neuronal networks.

Up-regulation of Ras/Raf/ERK1/2 signaling impairs cultured neuronal cell migration, neurogenesis, synapse formation, and dendritic spine development.

The Ras/Raf/ERK1/2 signaling pathway controls many cellular responses such as cell proliferation, migration, differentiation, and death. In the nervous system, emerging evidence also points to a death-promoting role for ERK1/2 in both in vitro and in vivo models of neuronal death. Recent studies have suggested that abnormal apoptosis in the central nervous system may be involved in the pathogenesis of autism.

Brain IL-6 elevation causes neuronal circuitry imbalances and mediates autism-like behaviors.

Abnormal immune responses have been reported to be associated with autism. A number of studies showed that cytokines were increased in the blood, brain, and cerebrospinal fluid of autistic subjects. Elevated IL-6 in autistic brain has been a consistent finding.

Upregulation of Ras/Raf/ERK1/2 signaling and ERK5 in the brain of autistic subjects.

Autism is a neurodevelopmental disorder characterized by impairments in social interaction, verbal communication and repetitive behaviors. A number of studies have shown that the Ras/Raf/ERK1/2 (extracellular signal-regulated kinase) signaling pathway plays important roles in the genesis of neural progenitors, learning and memory. Ras/Raf/ERK1/2 and ERK5 have also been shown to have death-promoting apoptotic roles in neural cells.

PRKX critically regulates endothelial cell proliferation, migration, and vascular-like structure formation.

Angiogenesis is a fundamental step in several important physiological events and pathological conditions including embryonic development, wound repair, tumor growth and metastasis. PRKX was identified as a novel type-I cAMP-dependent protein kinase gene expressed in multiple developing tissues. PRKX has also been shown to be phylogenetically and functionally distinct from PKA.

IL-6 is increased in the cerebellum of autistic brain and alters neural cell adhesion, migration and synaptic formation.

Background: Although the cellular mechanisms responsible for the pathogenesis of autism are not understood, a growing number of studies have suggested that localized inflammation of the central nervous system (CNS) may contribute to the development of autism. Recent evidence shows that IL-6 has a crucial role in the development and plasticity of CNS.

Methods: Immunohistochemistry studies were employed to detect the IL-6 expression in the cerebellum of study subjects.

Phosphorylation, protein kinases and ADPKD.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease characterized by renal cyst formation and caused by mutations in the PKD1 and PKD2 genes, which encode polycystin-1(PC-1) and -2 (PC-2) proteins, respectively. PC-1 is a large plasma membrane receptor involved in the regulation of several biological functions and signaling pathways including the Wnt cascade, AP-1, PI3kinase/Akt, GSK3β, STAT6, Calcineurin/NFAT and the ERK and mTOR cascades. PC-2 is a calcium channel of the TRP family.

A novel approach for characterization of cathepsin D protease and its effect on tau and β-amyloid proteins.

Cathepsin D is the lysosomal protease abundantly expressed in the brain. It plays an important role in the regulation of cellular apoptosis. In addition, cathepsin D has been shown to be involved in the pathogenesis of Alzheimer disease and autism.

BDNF-Akt-Bcl2 antiapoptotic signaling pathway is compromised in the brain of autistic subjects.

Although the pathogenesis of autism is not understood, emerging evidence points to apoptotic mechanisms being involved in this disorder. However, it is not known whether apoptosis signaling is deregulated in the brain of autistic subjects. This study investigates how the apoptosis-related proteins are regulated in the autistic brain.

Expression of inflammatory cytokines, Bcl2 and cathepsin D are altered in lymphoblasts of autistic subjects.

Unlabelled: To determine whether inflammation and apoptosis are involved in the pathogenesis of autism, we examined cytokines, Bcl2 expression and cathepsin D protease activity in the lymphoblasts of autistic subjects and age-matched controls. We found increased expression levels of pro-inflammatory cytokines TNF-α and IL-6, but decreased Bcl2 expression in lymphoblasts of autistic subjects. We also found that cathepsin D mRNA and protein expression were significantly increased in autistic lymphoblasts.

Cathepsin D and apoptosis related proteins are elevated in the brain of autistic subjects.

Autism is a severe neurodevelopmental disorder characterized by problems in communication, social skills, and repetitive behavior. Recent studies suggest that apoptotic mechanisms may partially contribute to the pathogenesis of this disorder. Cathepsin D is the predominant lysosomal protease and is abundantly expressed in the brain.

Elevated immune response in the brain of autistic patients.

Unlabelled: This study determined immune activities in the brain of ASD patients and matched normal subjects by examining cytokines in the brain tissue. Our results showed that proinflammatory cytokines (TNF-alpha, IL-6 and GM-CSF), Th1 cytokine (IFN-gamma) and chemokine (IL-8) were significantly increased in the brains of ASD patients compared with the controls. However the Th2 cytokines (IL-4, IL-5 and IL-10) showed no significant difference.

Diagnosis of depression in people with severe/profound intellectual disability.

The Marston 30 Symptoms Checklist for detecting depression was used to determine whether or not the notion of 'depressive equivalents' can provide a few of the core characteristics necessary for the diagnosis of depressive disorders in people with severe/profound intellectual disability (ID). Diagnoses of major depression were made by a psychiatrist using the DSM-III-R criteria, combined with information from records, staff, team, parents, behaviour profiles, direct observations, mental status and follow-up visits. Twenty-two people with ID fulfilled the selection criteria from a larger sample of 150 patients who had been evaluated in 350 contact visits.

Partial impairment of immune functions in peripheral blood leukocytes from aged men with Down's syndrome.

Down's syndrome (DS) has been considered a model of accelerated aging and of Alzheimer's disease. We investigated immunologic functions using peripheral blood leukocytes in order to correlate the production of cytokines and development of neuropathological changes of Alzheimer type in aged persons with DS. Cytokine production (IL-1beta, IL-2, IL-6, IL-8, and TNF-alpha), phytohemagglutinin (PHA)-stimulated proliferation of nonadherent monocytes, and superoxide anion production from polymorphonuclear leukocytes were measured.

Alterations in the immune system in cats fed diets with excess cystine.

As part of an ongoing biochemical study in nutrition we examined blood profiles, serum chemistry, lymphocyte transformation and lymphoid pathology in cats fed a diet containing 5% cystine with and without taurine. Automated blood counts of whole blood samples showed a decrease in red blood cell counts accompanied by a significant decrease in hemoglobin and hematocrit in cats fed 5% cystine in the absence of taurine compared to cats fed 0.05% taurine (control).

Diagnostic usefulness of cerebrospinal fluid in multiple sclerosis.

Multiple sclerosis (MS) is one of the most common demyelinating diseases of the central nervous system affecting adults between the ages of 20 and 40 years. Clinically, it is characterized by episodes of exacerbations and remissions. Although the cause of MS is unknown, it is generally believed that one or more infectious agents triggers an autoimmune response that causes myelin destruction.