Randal X. Moldrich

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To understand the aetiology and the phenotypic severity of Down syndrome, we searched for transcriptional signatures in a substructure of the brain (cerebellum) during post-natal development in a segmental trisomy 16 model, the Ts1Cje mouse. The goal of this study was to investigate the effects of trisomy on changes in gene expression across development(More)
The central nervous system of persons with Down syndrome presents cytoarchitectural abnormalities that likely result from gene-dosage effects affecting the expression of key developmental genes. To test this hypothesis, we have investigated the transcriptome of the cerebellum of the Ts1Cje mouse model of Down syndrome during postnatal development using(More)
Metabotropic glutamate (mGlu) receptors have multiple actions on neuronal excitability through G-protein-linked modifications of enzymes and ion channels. They act presynaptically to modify glutamatergic and gamma-aminobutyric acid (GABA)-ergic transmission and can contribute to long-term changes in synaptic function. The recent identification of(More)
The balance between self-renewal and differentiation of neural progenitor cells is an absolute requirement for the correct formation of the nervous system. Much is known about both the pathways involved in progenitor cell self-renewal, such as Notch signaling, and the expression of genes that initiate progenitor differentiation. However, whether these(More)
Several lines of evidence support a strong relationship between cholesterol and Alzheimer's disease pathogenesis. Membrane cholesterol is known to modulate amyloid precursor protein (APP) endocytosis and amyloid-beta (Abeta) secretion. Here we show in a human cell line model of endocytosis (HEK293 cells) that cholesterol exerts these effects in a(More)
Three members of the Nuclear Factor I (Nfi) gene family of transcription factors; Nfia, Nfib, and Nfix are highly expressed in the developing mouse brain. Nfia and Nfib knockout mice display profound defects in the development of midline glial populations and the development of forebrain commissures (das Neves et al. [1999] Proc Natl Acad Sci U S A(More)
Down syndrome is a chromosomal disorder caused by the presence of three copies of chromosome 21. The mechanisms by which this aneuploidy produces the complex and variable phenotype observed in people with Down syndrome are still under discussion. Recent studies have demonstrated an increased transcript level of the three-copy genes with some dosage(More)
Signal transduction mechanisms of group II metabotropic glutamate receptors (mGlu(2/3)) remains a matter of some controversy, therefore we sought to gain new insights into its regulation by studying cAMP production in cultured neurons and astrocytes, and by examining inter-relationships of mGlu(2/3)-induced signalling with cellular calcium and various(More)
The anticonvulsant activity of the selective group II metabotropic glutamate receptor (mGlu) agonist 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC) has been evaluated in chemoconvulsant and sound-induced models of epileptic seizures in DBA/2 mice. 2R,4R-APDC (> or =10 nmol, intracerebroventricularly (i.c.v.), -15 min) transiently reduced(More)
BACKGROUND AND PURPOSE In contrast to tissue-type plasminogen activator (tPA), vampire bat (Desmodus rotundus) salivary plasminogen activator (desmoteplase [DSPA]) does not promote excitotoxic injury when injected directly into the brain. We have compared the excitotoxic effects of intravenously delivered tPA and DSPA and determined whether DSPA can(More)