Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.4 (ribonuclease)
 6,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypothyroidism has devastating consequences on brain development. While the mechanisms that mediate these effects are not known, several lines of evidence suggest that a reduction in insulin-like growth factor-I (IGF-I) expression and/or action has a role. To assess whether reduced IGF-I expression and/or actions mediates the brain pathology of congenital hypothyroidism, we induced hypothyroidism by treating pregnant mice and lactating dams with 0. 1% propylthiouracil (PTU) in drinking water. Control and PTU-treated pups were sacrificed on postnatal day (P) 7, 10 and 14, and IGF-I mRNA expression was assessed in the cerebral cortex and cerebellum by ribonuclease protection assay. To control for mRNA loading, the signal of IGF-I protected bands was normalized to those for cyclophillin. IGF-I mRNA expression in hypothyroid animals was decreased significantly in cortex at P10 and P14 (42 and 60%, respectively). In the cerebellum, IGF-I mRNA expression was down-regulated at all ages studied, but the decrease was only statistically significant at P7 (31% decreased). We conclude that hypothyroidism alters IGF-I expression in the developing brain. Furthermore, we speculate that IGF-I plays a role in mediating some thyroid hormone actions during brain development.
 ...
PMID:Effects of hypothyroidism on insulin-like growth factor-I expression during brain development in mice. 1102 43

Although brain injury induced by undernutrition during early life is well described, the mechanisms that mediate the effects of undernutrition on brain development are not known. IGF-I plays an important role in the stimulation of postnatal somatic and brain growth. We have shown that IGF-I overexpression in brain ameliorates the effects of undernutrition on early postnatal brain growth, and thus, we postulated that alterations in IGF-I expression or action mediate the pathogenesis of malnutrition-induced brain injury. To begin to address this issue we evaluated the influence of undernutrition on brain IGF-I expression during early postnatal development in mice. Undernutrition was induced in mice by separating half of the pups in each litter from their lactating dams for a defined period each day. Pups were killed at postnatal day (P) 7, P14, P21, and P28. The changes in IGF-I mRNA were quantified by ribonuclease protection assay. At P7 IGF-I mRNA abundance in undernourished animals was increased in cerebral cortex (223% of controls), but decreased in diencephalon (36% of controls). At P14, IGF-I mRNA abundance was increased in diencephalon (230% of controls). Although there were no other statistically significant alterations of IGF-I mRNA in undernourished mice, IGF-I abundance in the cerebral cortex appeared increased at P14 (142% of controls), and in cerebellum it was consistently but modestly decreased (78 and 59% of controls) from P7 to P21, respectively. We conclude that nutrition regulates murine brain IGF-I expression in a developmentally specific fashion that is dependent on the region of expression. Importantly, the influence of undernutrition on IGF-I expression is markedly different in the brain than in liver, where nutritional deficiency profoundly decreases IGF-I expression. We speculate that the relative preservation of or increases in regional brain IGF-I expression explain, at least in part, the well-known finding that undernutrition during early postnatal development has less marked growth-retarding effects on the brain than it does on the soma.
 ...
PMID:Nutritional regulation of IGF-I expression during brain development in mice. 1115 13

It is widely believed that expression of the vesicular glutamate transporter genes VGLUT1 and VGLUT2 is restricted to glutamatergic neurons and that the two transporters segregate in different sets of neurons. Using single-cell multiplex RT-PCR (sc-RT-mPCR), we show that VGLUT1 and VGLUT2 mRNAs were coexpressed in most of the sampled neurons from the rat hippocampus, cortex, and cerebellum at postnatal Day (P)14 but not P60. In accordance, changes in VGLUT1 and VGLUT2 mRNA concentrations were found to occur in these and other brain areas between P14 and P60, as revealed by semiquantitative RT-PCR and quantitated by ribonuclease protection assay. VGLUT1 and -2 coexpression in the hippocampal formation is supported further by in situ hybridization data showing that virtually all cells in the CA1-CA3 pyramidal and granule cell layers were highly positive for both transcripts until P14. It was revealed using sc-RT-mPCR that transcripts for VGLUT1 and VGLUT2 were also present in neurons of the cerebellum, striatum, and septum that expressed markers for gamma-aminobutyric acid (GABA)ergic or cholinergic phenotypes, as well as in hippocampal cells containing transcripts for the glial fibrillary acidic protein. Our study suggests that VGLUT1 and VGLUT2 proteins may often transport glutamate into vesicles within the same neuron, especially during early postnatal development, and that they are expressed widely in presumed glutamatergic, GABAergic, and cholinergic neurons, as well as in astrocytes. Furthermore, our study shows that such coexpressing neurons remain in the adult brain and identifies several areas that contain them in both young and adult rats.
 ...
PMID:Frequent coexpression of the vesicular glutamate transporter 1 and 2 genes, as well as coexpression with genes for choline acetyltransferase or glutamic acid decarboxylase in neurons of rat brain. 1598 96