ABSTRACT
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Subject(s)
Humans , Coronary Disease/classification , Myocardial Infarction/classification , Troponin I/isolation & purification , Troponin T/isolation & purification , Myocardial Infarction/physiopathology , Endothelium, Vascular/physiopathology , Coronary Disease/physiopathology , Myocardial Reperfusion , alpha-Macroglobulins/antagonists & inhibitorsABSTRACT
Using quantitative in situ hybridization, a significant decrease in expression of proenkephalin (27.1%) and of protachykinin mRNAs (20.0%) is observed in the rat caudate-putamen 14 days after daily intraperitoneal administration of N-methyl-D-aspartate receptor antagonist MK-801, 2 mg/kg.
Subject(s)
Dizocilpine Maleate/pharmacology , Enkephalins/biosynthesis , Excitatory Amino Acid Antagonists/pharmacology , Neostriatum/metabolism , Protein Precursors/biosynthesis , RNA, Messenger/biosynthesis , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Tachykinins/biosynthesis , Animals , Autoradiography , Dizocilpine Maleate/administration & dosage , Down-Regulation/drug effects , Excitatory Amino Acid Antagonists/administration & dosage , In Situ Hybridization , Injections, Intraperitoneal , Male , Neostriatum/drug effects , Rats , Rats, WistarABSTRACT
delta-9-Tetrahydrocannabinol (THC) is a major psychoactive component of cannabis. We here studied, by quantitative in situ hybridization at the macroscopic level, the possible modulatory effects of acute THC (5 mg/kg/i.p.) on gene expression of the growth factor pleiotrophin (PTN) in the adult rat forebrain. We found, 30 min after a single injection of THC, a significant increase of PTN mRNA concentrations in the cingulate cortex (38%), fronto-parietal cortex (31%) and caudate-putamen (27%). In conclusion, this is the first report on THC regulation of growth factor gene expression in the brain.
Subject(s)
Carrier Proteins/biosynthesis , Cytokines/biosynthesis , Dronabinol/pharmacology , Gene Expression Regulation/drug effects , Nerve Growth Factors/biosynthesis , Prosencephalon/metabolism , Animals , Male , Organ Specificity , Prosencephalon/drug effects , RNA, Messenger/analysis , RNA, Messenger/biosynthesis , Rats , Rats, WistarABSTRACT
A small surgical lesion of the parietal cortex induces an increase in the expression of several messenger RNAs varying from 172 to 980% in the entire homolateral cerebral cortex, as detected by quantitative in situ hybridization histochemistry. The messenger RNAs encoding the immediate early genes of the leucine zipper family (c-fos, c-jun, jun-B), the Zinc finger family (zif268), the glucocorticoid receptor family (NGFI-B) and the interferon family (PC4) are increased within 2 h after the lesion and return to normal levels at 6 h. The messenger RNAs encoding cholecystokinin, neuropeptide Y, somatostatin and the synthetizing enzyme of the neurotransmitter GABA, glutamate decarboxylase, are elevated within one day and return to normal levels after six days. An intraperitoneal injection of the N-methyl-D-aspartate receptor antagonist dizocilpine maleate, 30 min before surgery, prevented either the induction of immediate early gene expression or the increase of neuropeptide and glutamate decarboxylase messenger RNA expression. This study demonstrates that a minimal cortical lesion induces extensive changes in gene expression and that the mechanism(s) leading to these changes involves the action of glutamate at the N-methyl-D-aspartate receptor. These modifications may be of importance in explaining diffuse changes not related to neuronal circuitry in several conditions.
Subject(s)
Cerebral Cortex/metabolism , Dizocilpine Maleate/pharmacology , Genes, Immediate-Early , Genes, fos , Genes, jun , Glutamates/physiology , Immediate-Early Proteins , N-Methylaspartate/antagonists & inhibitors , Nerve Tissue Proteins/biosynthesis , Neurotransmitter Agents/biosynthesis , Parietal Lobe/injuries , Animals , Cerebral Infarction/physiopathology , Cholecystokinin/biosynthesis , Cholecystokinin/genetics , DNA-Binding Proteins/biosynthesis , DNA-Binding Proteins/genetics , Early Growth Response Protein 1 , Female , Gene Expression Regulation , Glutamate Decarboxylase/biosynthesis , Glutamate Decarboxylase/genetics , Glutamic Acid , Leucine Zippers/genetics , Membrane Proteins/biosynthesis , Membrane Proteins/genetics , Nerve Tissue Proteins/genetics , Neuropeptide Y/biosynthesis , Neuropeptide Y/genetics , Nuclear Receptor Subfamily 4, Group A, Member 1 , Rats , Rats, Wistar , Receptors, Cytoplasmic and Nuclear , Receptors, Steroid , Somatostatin/biosynthesis , Somatostatin/genetics , Time Factors , Transcription Factors/biosynthesis , Transcription Factors/genetics , Zinc Fingers/geneticsABSTRACT
The release of intracellular Ca, which is involved in many neuronal functions, is regulated by the second messenger inositol 1,4,5-trisphosphate (InsP3) interacting with specific receptor. The distribution of the mRNA coding for the recently cloned InsP3 receptor was studied in the developing rat brain using oligonucleotides derived from the rat cDNA sequence and in situ hybridization. The localizations of the mRNA in the postnatal brain were exactly superimposable to that previously reported in the adult [Mailleux et al., Neuroscience, 49 (1992)577-590]. Higher mRNA levels were consistently found in the adult neurons over their postnatal counterpart. Hybridization signal was first visible in the cerebellar Purkinje cells which express dramatically higher mRNA levels of the receptor than any other neurons in the brain. In conclusion, the levels of InsP3 receptor mRNA per neuron increased with synaptogenesis. This finding suggests the occurrence during this critical developmental period of a more complex regulation of Ca fluxes, perhaps requiring higher intraneuronal levels of InsP3 receptor.
Subject(s)
Aging/metabolism , Brain/metabolism , Calcium Channels/biosynthesis , Gene Expression , Inositol 1,4,5-Trisphosphate/metabolism , Purkinje Cells/metabolism , RNA, Messenger/metabolism , Receptors, Cytoplasmic and Nuclear/biosynthesis , Animals , Animals, Newborn , Autoradiography/methods , Brain/growth & development , Cerebellum/growth & development , Embryo, Mammalian , Inositol 1,4,5-Trisphosphate Receptors , Oligonucleotide Probes , Organ Specificity , Rats , Rats, Wistar , Sulfur RadioisotopesABSTRACT
The calcium-mobilizing second messenger inositol 1,4,5-trisphosphate (InsP3) is phosphorylated to inositol 1,3,4,5-tetrakisphosphate, another putative second messenger, through the activity of the enzyme InsP3 3-kinase. The cDNAs encoding two such isozymes have been recently isolated from a human hippocampal cDNAs library. We have previously reported the neuronal localization of the A form (Mailleux et al., Neurosci. Lett., 137 (1992) 69-71) and we here demonstrate the presence of the messenger RNA for the B form in human astrocytes.
Subject(s)
Astrocytes/enzymology , Brain/enzymology , Isoenzymes/genetics , Phosphotransferases (Alcohol Group Acceptor) , Phosphotransferases/genetics , RNA, Messenger/metabolism , Adult , Aged , Aged, 80 and over , Cerebellar Cortex/enzymology , DNA Probes , Female , Humans , Male , Oligonucleotide Probes , RNA, Messenger/analysis , Sulfur RadioisotopesABSTRACT
The distribution of the messenger RNA coding for the recently cloned inositol 1,4,5-trisphosphate (InsP3) 3-kinase, the enzyme phosphorylating InsP3 to InsP4, was compared to the localizations of InsP3 receptor mRNA in the human brain using in situ hybridization histochemistry and oligonucleotide probes. InsP3 3-kinase and receptor mRNA levels were high in the cerebellar Purkinje cells. They were also observed, to a much lesser degree than in the cerebellum, in the hippocampal CA1 pyramidal cells and dentate gyrus granule cells, in the majority of the cortical neurons and in the striatal medium-sized neurons. Both mRNAs were not detected in the brainstem and in the glial cells.
