Abnormal Microglial Density and Morphology in the Brain of Cyclooxygenase 2 Knockin Mice.

Prostaglandin E2 (PGE2) is a signaling molecule produced by cyclooxygenase-2 (COX-2) that is important in healthy brain development. Anomalies in the COX-2/PGE2 pathway due to genetic or environmental factors have been linked to Autism Spectrum Disorders (ASD). Our previous studies showed that COX-2 deficient (COX-2KI) mice exhibit sex-dependent molecular changes in the brain and associated autism-related behaviors.

Abnormal dendritic morphology in the cerebellum of cyclooxygenase-2 knockin mice.

Prostaglandin E2 (PGE2) is a bioactive signalling molecule metabolized from the phospholipid membranes by the enzymatic activity of cycloxygenase-2 (COX-2). In the developing brain, COX-2 constitutively regulates the production of PGE2, which is important in neuronal development. However, abnormal COX-2/PGE2 signalling has been linked to neurodevelopmental disorders including autism spectrum disorders (ASDs).

Prostaglandin E2 Increases Neurite Length and the Formation of Axonal Loops, and Regulates Cone Turning in Differentiating NE4C Cells Via PKA.

Prostaglandin E2 (PGE2) is a membrane-derived lipid signaling molecule important in neuronal development. Abnormal levels of PGE2, due to environmental insults prenatal development, have been linked to brain pathologies. We have previously shown that the addition of PGE2 to neuroectodermal (NE4C) stem cells affects early stages of neuronal differentiation (day 0-8) including increased stem cell motility, accelerated formation of neurospheres, and elevated calcium levels in growth cones.

Autism-related behaviors in the cyclooxygenase-2-deficient mouse model.

Prostaglandin E2 (PGE2) is an endogenous lipid molecule involved in normal brain development. Cyclooxygenase-2 (COX2) is the main regulator of PGE2 synthesis. Emerging clinical and molecular research provides compelling evidence that abnormal COX2/PGE2 signaling is associated with autism spectrum disorder (ASD).

Maternal exposure to prostaglandin E modifies expression of Wnt genes in mouse brain - An autism connection.

Prostaglandin E (PGE) is a lipid signaling molecule important for brain development and function. Various genetic and environmental factors can influence the level of PGE and increase the risk of developing Autism Spectrum Disorder (ASD). We have previously shown that in neuronal cell lines and mouse brain, PGE can interfere with the Wnt canonical pathway, which is essential during early brain development.

Microarray analysis of gene expression in the cyclooxygenase knockout mice - a connection to autism spectrum disorder.

The cellular and molecular events that take place during brain development play an important role in governing function of the mature brain. Lipid-signalling molecules such as prostaglandin E (PGE ) play an important role in healthy brain development. Abnormalities along the COX-PGE signalling pathway due to genetic or environmental causes have been linked to autism spectrum disorder (ASD).

Prostaglandin E2 promotes neural proliferation and differentiation and regulates Wnt target gene expression.

Prostaglandin E2 (PGE2 ) is an endogenous lipid molecule that regulates important physiological functions, including calcium signaling, neuronal plasticity, and immune responses. Exogenous factors such as diet, exposure to immunological agents, toxic chemicals, and drugs can influence PGE2 levels in the developing brain and have been associated with autism disorders. This study seeks to determine whether changes in PGE2 level can alter the behavior of undifferentiated and differentiating neuroectodermal (NE-4C) stem cells and whether PGE2 signaling impinges on the Wnt/β-catenin pathways.

Prostaglandin E2 facilitates subcellular translocation of the EP4 receptor in neuroectodermal NE-4C stem cells.

Prostaglandin E2 (PGE) is a lipid mediator released from the phospholipid membranes that mediates important physiological functions in the nervous system via activation of four EP receptors (EP1-4). There is growing evidence for the important role of the PGE/EP4 signaling in the nervous system. Previous studies in our lab show that the expression of the EP4 receptor is significantly higher during the neurogenesis period in the mouse.

Prostaglandin E2 elevates calcium in differentiated neuroectodermal stem cells.

Lipid mediator prostaglandin E2 (PGE2) is an endogenous signaling molecule that plays an important role during early development of the nervous system. Abnormalities in the PGE2 signaling pathway have been associated with neurodevelopmental disorders such as autism spectrum disorders. In this study we use ratiometric fura-2AM calcium imaging to show that higher levels of PGE2 elevate intracellular calcium levels in the cell soma and growth cones of differentiated neuroectodermal (NE-4C) stem cells.

Prenatal exposure to common environmental factors affects brain lipids and increases risk of developing autism spectrum disorders.

The prevalence of autism spectrum disorders (ASDs) has been on the rise over recent years. The presence of diverse subsets of candidate genes in each individual with an ASD and the vast variability of phenotypical differences suggest that the interference of an exogenous environmental component may greatly contribute to the development of ASDs. The lipid mediator prostaglandin E2 (PGE2 ) is released from phospholipids of cell membranes, and is important in brain development and function; PGE2 is involved in differentiation, synaptic plasticity and calcium regulation.

Transcriptional regulation by FOXP1, FOXP2, and FOXP4 dimerization.

FOXP1, FOXP2, and FOXP4 are three members of the FOXP gene subfamily of transcription factors involved in the development of the central nervous system. Previous studies have shown that the transcriptional activity of FOXP1/2/4 is regulated by homo- and heterodimerization. However, their transcriptional gene targets in the developing brain are still largely unknown.

Prostaglandin E2 alters Wnt-dependent migration and proliferation in neuroectodermal stem cells: implications for autism spectrum disorders.

Prostaglandin E2 (PGE2) is a natural lipid-derived molecule that is involved in important physiological functions. Abnormal PGE2 signalling has been associated with pathologies of the nervous system. Previous studies provide evidence for the interaction of PGE2 and canonical Wnt signalling pathways in non-neuronal cells.

Developmental expression of P5 ATPase mRNA in the mouse.

P(5) ATPases (ATP13A1 through ATP13A5) are found in all eukaryotes. They are currently poorly characterized and have unknown substrate specificity. Recent evidence has linked two P(5) ATPases to diseases of the nervous system, suggesting possible importance of these proteins within the nervous system.

The neurobiology of lipid metabolism in autism spectrum disorders.

Autism is a neurodevelopmental disorder characterized by impairments in communication and reciprocal social interaction, coupled with repetitive behavior, which typically manifests by 3 years of age. Multiple genes and early exposure to environmental factors are the etiological determinants of the disorder that contribute to variable expression of autism-related traits. Increasing evidence indicates that altered fatty acid metabolic pathways may affect proper function of the nervous system and contribute to autism spectrum disorders.

Misoprostol elevates intracellular calcium in Neuro-2a cells via protein kinase A.

Misoprostol, a prostaglandin type E analogue, has been implicated in a number of neurodevelopmental disorders. However, its mode of action in the nervous system is not well understood. Misoprostol acts on the same receptors as prostaglandin E(2) (PGE(2)), a natural lipid-derived compound, which mediates important physiological functions in the nervous system via activation of four EP receptors (EP1-4).

Prostaglandin E(2) and misoprostol induce neurite retraction in Neuro-2a cells.

Prostaglandin E(2) (PGE(2)) is a key lipid-derived compound which mediates important physiological functions in the nervous system via activation of four EP receptors (EP1-4). Recent studies have shown that altered PGE(2) signalling due to abnormal lipid peroxidation and oxidative stress may underlie some pathologies of the nervous system. The prenatal exposure to the drug misoprostol, a prostaglandin type E analogue, has also been linked to a number of neurodevelopmental defects.

The E646D-ATP13A4 mutation associated with autism reveals a defect in calcium regulation.

ATP13A4 is a member of the subfamily of P5-type ATPases. P5-type ATPases are the least studied of the P-type ATPase subfamilies with no ion specificities assigned to them. In order to elucidate ATP13A4 function, we studied the protein's subcellular localization and tested whether it is involved in calcium regulation.