Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.30.1 (S1 nuclease)
 3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The development of the spinal cord involves the proliferation of neurons, their migration to well-defined areas, fiber outgrowth and synapse formation. The present study was designed to correlate the spatiotemporal pattern of expression of synaptophysin, an integral membrane protein of small synaptic vesicles, with these basic processes occurring during the embryonic development of the rat spinal cord. Thoracic segments of spinal cords from embryonic days 12, 14, 16, 18, 20 and of adult spinal cords were studied. S1 nuclease protection assays and immunoblots revealed minute amounts of specific mRNA and synaptophysin at embryonic day 12. There was a steep increase of mRNA between embryonic days 14 and 16, after which levels reached a plateau. A rise in the amount of synaptophysin in the spinal cord occurred between embryonic days 12 and 14, and the levels changed only slightly until the end of embryonic development. Even higher levels of synaptophysin, found in the adult spinal cord, may indicate that its biosynthesis continued after birth. In situ hybridization histochemistry revealed the localization of specific synaptophysin mRNA in the neuroepithelium. However, immunocytochemistry failed to detect synaptophysin in the neuroepithelial cells. Following migration of the neuroblasts, synaptophysins was found in neurons concomitantly with the onset of fiber outgrowth. Thus, already at embryonic day 12, outgrowing fibers of the dorsal root sensory neurons and of motoneurons were synaptophysin positive. From embryonic day 14 throughout the prenatal period, strong synaptophysin immunoreactivity was seen in the ventrolateral and dorsal parts of the marginal layer. Most likely this staining pattern indicates transient functional synaptic contacts because, in the adult spinal cord, the corresponding region, the white matter, exhibited only faint synaptophysin immunoreactivity. In the intermediate layer of the embryonic spinal cord, which corresponds to the gray matter of the adult spinal cord, synaptophysin-positive fibers were observed prior to the formation of functional synapses. The latter are most likely permanent, since synaptophysin in the adult spinal cord is mainly confined to the gray matter. Our data (i) show transcription and translation of synaptophysin within the neurons of the spinal cord and correlate these processes with proliferation, migration, fiber outgrowth and the formation of transient or permanent synapses, and (ii) prove that synaptophysin is a marker for fiber outgrowth in addition to synapse formation.
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PMID:Expression of synaptophysin during the prenatal development of the rat spinal cord: correlation with basic differentiation processes of neurons. 191 Jan 56

Alpha-synuclein is an evolutionary highly conserved neuronal protein localized in presynaptic nerve terminals. The protein has been suggested to be involved in the pathogenesis of neurodegenerative diseases, but little is known about the physiological function of the protein. In the present study we used newborn, three, 14, 93 and 710-day-old rats to examine the expression of alpha-synuclein messenger RNA and protein during development of the hippocampus and cerebral cortex. Using in situ hybridization and an S1 nuclease protection assay, we found a high expression of alpha-synuclein messenger RNA during early postnatal development, followed by a marked decrease between postnatal days 14 and 93. In contrast, the amount of alpha-synuclein protein, as determined by immunoblotting, continued to increase throughout development and remained at a high level for at least two years. The persistent high expression of alpha-synuclein protein throughout development suggests that the protein is involved in maintaining synaptic function. Furthermore, the discrepancy between the levels of alpha-synuclein messenger RNA and protein after postnatal day 14 indicates that the amount of alpha-synuclein is determined by post-transcriptional regulation, and not by messenger RNA expression alone. To estimate the changes of alpha-synuclein expression per synapse, we compared the developmental expression of alpha-synuclein with synaptophysin, a well-established synaptic marker. The alpha-synuclein/synaptophysin messenger RNA and protein ratio was high during early development, but low in adult (postnatal day 93) and old (postnatal day 710) rats. This could indicate a higher expression of alpha-synuclein per synapse during early development.
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PMID:Developmental expression of alpha-synuclein in rat hippocampus and cerebral cortex. 1036 22

Apolipoprotein E (apoE) isoforms are key determinants of susceptibility to late-onset Alzheimer's disease (AD). The epsilon 4 and epsilon 2 alleles have been associated with increased and decreased risk for AD, respectively. We have generated and characterized transgenic mice in which the human apoE2 gene is expressed under the control of the platelet-derived growth factor B-chain (PDGF-B) promoter, or the transferrin (TF) promoter. S1 nuclease analysis and immunoblotting showed that the PDGF-B apoE2 mice express apoE2 exclusively in the brain whereas the TF apoE2 mice express apoE2 in the liver and in the brain. In the TF apoE2 mouse line, apoE2 is also detected in the plasma. The PDGF-B apoE2 and the TF apoE2 transgenic mice were bred back to apoE(-)(/)(-) background. Immunohistochemical analysis showed that the PDGF apoE2 x apoE(-)(/)(-) and the TF apoE2 x apoE(-)(/)(-) mice express human apoE2 within the neocortex in hippocampal neurons and glial cells, respectively. ApoE(-)(/)(-) mice have been shown to develop age-dependent loss of synaptophysin. Immunoblotting of mouse brain extracts and immunohistochemical analysis of brain sections showed that apoE expression in both apoE2 x apoE(-)(/)(-) transgenic lines was associated with significant recovery of brain synaptophysin levels as compared to the levels of apoE(-)(/)(-) littermates of the same age. These apoE2-expressing mice, when bred back on amyloid precursor protein (APP) transgenic mice or other mouse lines featuring alterations in lipoprotein metabolism, may provide new mouse models for elucidating the role of apoE2 in lipid homeostasis in the brain and in the pathogenesis of AD.
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PMID:Generation and characterization of two transgenic mouse lines expressing human ApoE2 in neurons and glial cells. 1213 50