Altered Gene Expression of Thyroid Hormone Transporters and Deiodinases in iPS MeCP2-Knockout Cells-Derived Neurons.

MeCP2 is an X-linked gene; its mutation causes Rett Syndrome (RTT), a severe neurodevelopmental disability that affects mainly girls. Acting as a transcription factor, the MeCP2 protein is able to regulate several hormone-related genes, such as the thyroid hormones (TH), which are known to play an important role in the development of the central nervous system (CNS). Although only a few studies have associated RTT and TH, TH deficit can lead to neurological deregulation by triggering functional deficiencies during adulthood.

Modeling the Interplay Between Neurons and Astrocytes in Autism Using Human Induced Pluripotent Stem Cells.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with unclear etiology and imprecise genetic causes. The main goal of this work was to investigate neuronal connectivity and the interplay between neurons and astrocytes from individuals with nonsyndromic ASD using induced pluripotent stem cells.

Methods: Induced pluripotent stem cells were derived from a clinically well-characterized cohort of three individuals with nonsyndromic ASD sharing common behaviors and three control subjects, two clones each.

Autism spectrum disorders and disease modeling using stem cells.

Autism spectrum disorders (ASD) represent a variety of disorders characterized as complex lifelong neurodevelopment disabilities, which may affect the ability of communication and socialization, including typical comportments like repetitive and stereotyped behavior. Other comorbidities are usually present, such as echolalia, hypotonia, intellectual disability and difficulties in processing figured speech. Furthermore, some ASD individuals may present certain abilities, such as eidetic memory, outstanding musical or painting talents and special mathematical skills, among others.

TRPC Channels and Mental Disorders.

Transient receptor potential canonical (TRPC) channels mediate the influx of different types of cations through the cell membrane and are involved in many functions of the organism. Evidences of involvement of TRPC channels in neuronal development suggest that this family of proteins might play a role in certain neurological disorders. As reported, knockout mice for different TRPC channels show alterations in neuronal morphological and functional parameters, with behavioral abnormalities, such as in exploratory and social behaviors.

XPC deficiency is related to APE1 and OGG1 expression and function.

Oxidative DNA damage is considered to be a major cause of neurodegeneration and internal tumors observed in syndromes that result from nucleotide excision repair (NER) deficiencies, such as Xeroderma Pigmentosum (XP) and Cockayne Syndrome (CS). Recent evidence has shown that NER aids in removing oxidized DNA damage and may interact with base excision repair (BER) enzymes. Here, we investigated APE1 and OGG1 expression, localization and activity after oxidative stress in XPC-deficient cells.

The Human Model: Changing Focus on Autism Research.

The lack of live human brain cells for research has slowed progress toward understanding the mechanisms underlying autism spectrum disorders. A human model using reprogrammed patient somatic cells offers an attractive alternative, as it captures a patient's genome in relevant cell types. Despite the current limitations, the disease-in-a-dish approach allows for progressive time course analyses of target cells, offering a unique opportunity to investigate the cellular and molecular alterations before symptomatic onset.

The Use of Induced Pluripotent Stem Cell Technology to Advance Autism Research and Treatment.

Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders sharing a core set of symptoms, including impaired social interaction, language deficits, and repetitive behaviors. While ASDs are highly heritable and demonstrate a clear genetic component, the cellular and molecular mechanisms driving ASD etiology remain undefined. The unavailability of live patient-specific neurons has contributed to the difficulty in studying ASD pathophysiology.

Treadmill exercise induces age-related changes in aversive memory, neuroinflammatory and epigenetic processes in the rat hippocampus.

It has been described that exercise can modulate both inflammatory response and epigenetic modifications, although the effect of exercise on these parameters during the normal brain aging process yet remains poorly understood. Here, we investigated the effect of aging and treadmill exercise on inflammatory and epigenetic parameters specifically pro and anti-inflammatory cytokines levels, activation of NF-kB and histone H4 acetylation levels in hippocampus from Wistar rats. Additionally, we evaluated aversive memory through inhibitory avoidance task.

Exercise induces age-dependent changes on epigenetic parameters in rat hippocampus: a preliminary study.

Regular exercise improves learning and memory, including during aging process. Interestingly, the imbalance of epigenetic mechanisms has been linked to age-related cognitive deficits. However, studies about epigenetic alterations after exercise during the aging process are rare.

A quantitative proteomic and transcriptomic comparison of human mesenchymal stem cells from bone marrow and umbilical cord vein.

Human mesenchymal stem cells (hMSCs) are adult multipotent cells that have high therapeutic potential due to their immunological properties. They can be isolated from several different tissues with bone marrow (BM) being the most common source. Because the isolation procedure is invasive, other tissues such as human umbilical cord vein (UCV) have been considered.

Modeling neurodevelopmental disorders using human neurons.

The cellular and molecular mechanisms of neurodevelopmental conditions such as autism spectrum disorders have been studied intensively for decades. The unavailability of live patient neurons for research, however, has represented a major obstacle in the elucidation of the disease etiologies. Recently, the development of induced pluripotent stem cell (iPSC) technology allows for the generation of human neurons from somatic cells of patients.

Evidence for premature aging due to oxidative stress in iPSCs from Cockayne syndrome.

Cockayne syndrome (CS) is a human premature aging disorder associated with neurological and developmental abnormalities, caused by mutations mainly in the CS group B gene (ERCC6). At the molecular level, CS is characterized by a deficiency in the transcription-couple DNA repair pathway. To understand the role of this molecular pathway in a pluripotent cell and the impact of CSB mutation during human cellular development, we generated induced pluripotent stem cells (iPSCs) from CSB skin fibroblasts (CSB-iPSC).

Autophagy in stem cell maintenance and differentiation.

Autophagy is a lysosome-dependent degradation pathway that allows cells to recycle damaged or superfluous cytoplasmic content, such as proteins, organelles, and lipids. As a consequence of autophagy, the cells generate metabolic precursors for macromolecular biosynthesis or ATP generation. Deficiencies in this pathway were associated to several pathological conditions, such as neurodegenerative and cardiac diseases, cancer, and aging.

Modeling epilepsy with pluripotent human cells.

Pluripotency is generally defined by the ability to differentiate into cell types representing all three germ layers: ectoderm, mesoderm, and endoderm. Human pluripotent stem cells hold great promise in regenerative medicine and in cell replacement therapies because of their ability to self-renew and their developmental potential to become all cell types in the body. Moreover, pluripotent cells represent a unique system in which to study the normal development of the human nervous system and the several instances where the process may fail.

Skeletal muscle cells expressing VEGF induce capillary formation and reduce cardiac injury in rats.

Background: We tested a preemptive combined cell/gene therapy strategy of skeletal myoblasts transfected with Ad(5)RSVVEGF-165 in an ischemia/reperfusion rat model to increase collateral blood flow to nonischemic heart tissue.

Methods: Lewis rats were injected with placebo (Control), 10(6) skeletal myoblasts (SkM), or 10(6) skeletal myoblasts transfected with Ad(5)RSVVEGF-165 (SkM(+)) into the left ventricle 1week before ischemia. Left ventricle end-diastolic pressure, scar area, and capillary density were assessed 4weeks later.

Restoring DNA repair capacity of cells from three distinct diseases by XPD gene-recombinant adenovirus.

The nucleotide excision repair (NER) is one of the major human DNA repair pathways. Defects in one of the proteins that act in this system result in three distinct autosomal recessive syndromes: xeroderma pigmentosum (XP), Cockayne syndrome (CS) and trichothiodystrophy (TTD). TFIIH is a nine-protein complex essential for NER activity, initiation of RNA polymerase II transcription and with a possible role in cell cycle regulation.

Complementation of the DNA repair deficiency in human xeroderma pigmentosum group a and C cells by recombinant adenovirus-mediated gene transfer.

Nucleotide excision repair (NER) is one of the most versatile DNA repair mechanisms, ensuring the proper functioning and trustworthy transmission of genetic information in all living cells. The phenotypic consequences caused by NER defects in humans are autosomal recessive diseases such as xeroderma pigmentosum (XP). This syndrome is the most sun-sensitive disorder leading to a high frequency of skin cancer.