Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Electrical stimulation of the Schaffer-collateral axonal system under conditions which do not elicit detectable seizure activity causes an increase in the activity of ornithine decarboxylase (ODC), the rate limiting enzyme of polyamine synthesis, in the hippocampus, olfactory cortex, neocortex and olfactory bulb. The degree of ODC activation is dependent upon the stimulus parameters. The results support the hypothesis that neuronal activity regulates hippocampal polyamine concentrations.
Brain Res Mol Brain Res 1990 Feb
PMID:Induction of ornithine decarboxylase by subseizure stimulation in the hippocampus in vivo. 216 44

Antibodies are used to localize the NGFI-A protein in the rat brain. The protein is found in a wide variety of neurons. However, not all neurons are stained. The protein is either absent or present at undetectable levels in glial cells. Neuronal nuclei stain intensely, cytoplasmic staining is lighter. Seizures cause a detectable increase in the intensity of staining.
Brain Res Mol Brain Res 1990 Jul
PMID:Localization of the NGFI-A protein in the rat brain. 216 69

Extracellular adenosine acts through specific cell surface receptors to modulate numerous physiological processes in both the CNS and peripheral tissues (e.g. neurotransmitter release and blood flow). Activation of A1 or A2 adenosine receptors leads to decreased or increased intracellular cAMP levels, respectively. Fos and Jun are nuclear proto-oncogene products, which, like cAMP, appear to act as intermediates in a number of signal transduction pathways. Since increases in both adenosine release and Fos and Jun expression occur in the brain following seizures, we wanted to determine whether Fos and Jun induction might occur as a result of adenosine receptor activation. 3T3 fibroblasts and NG108-15 neuroblastoma-glioma hybrid cells were chosen for study, since they were known to respond to adenosine agonists with changes in cAMP levels. The membranes of NG108-15 cells were shown to have A2-like binding activity in a competitive binding assay. Cultures of each cell line were treated with the adenosine agonists, CHA (A1-selective) and NECA (non-selective adenosine agonist). Both lines responded with a concentration-dependent transient increase in c-fos, but not c-jun, mRNA content after treatment with either agonist. The kinetics of the response were much more rapid for 3T3 cells (peak between 15 and 30 min) than for NG cells (peak between 60 and 90 min). The slower, more prolonged response in the NG108-15 cells is more similar to the time interval between adenosine release and the peak of c-fos mRNA induction in brains of animals following the administration of seizure-promoting drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Res Mol Brain Res 1990 Oct
PMID:Activation of adenosine receptors induces c-fos, but not c-jun, expression in neuron-glia hybrids and fibroblasts. 217 6

The NGFI-B cDNA was previously isolated by virtue of its induction by nerve growth factor (NGF) in PC12 cells. It encodes a 61-kilodalton protein that has two regions of extensive homology with members of the steroid/thyroid hormone receptor gene family. The rat NGFI-B gene is approximately 7.6 kilobases long and is interrupted by six introns. Although the exon-intron structure of the gene is similar to those of several other members of the steroid/thyroid hormone receptor gene family, there is a novel splice site within the DNA-binding domain which suggests that NGFI-B constitutes yet another evolutionary digression from a postulated common ancestral receptor gene. Primer extension and S1 nuclease protection assays were used to determine the transcription initiation site, which displayed the heterogeneity typical of genes that lack a TATA box. Sequence analysis of the 5' flanking region revealed several GC boxes but no identifiable TATA box. Four potential AP1 binding sites were identified at nucleotides -49, -78, -222, and -242. Neither the serum response element nor the CArG box element, two sequences found in other growth factor-inducible genes, was detected in this region of the growth factor-inducible NGFI-B gene. Nevertheless, results of nuclear runoff experiments demonstrated that the NGFI-B gene was transcriptionally activated by nerve growth factor in PC12 cells. In vivo, a rapid, dramatic increase in NGFI-B mRNA was observed in the cerebral cortex, midbrain, and cerebellum of animals that experienced a convulsant-induced seizure.
Mol Cell Biol 1989 Oct
PMID:The NGFI-B gene, a transcriptionally inducible member of the steroid receptor gene superfamily: genomic structure and expression in rat brain after seizure induction. 247 23

Among a series of 44 transgenic families established after microinjection into fertilized eggs of a plasmid DNA where the structural gene for the large T antigen of polyoma virus is located downstream from the viral early promoter-enhancer region, one family with a hereditary neurological disorder was observed. At about three weeks of age, these animals developed a syndrome of constant tremor with recurrent seizures. Histological and ultra-structural examination revealed extensive dysmyelination in the white matter of the brain stem, cerebellum and spinal cord, as well as of peripheral nerves. This phenotype is reminiscent of that of the mouse "twitcher" (twi) mutant and of the human hereditary leukodystrophies. Expression of the viral sequences, assayed by Northern analysis and immunolabeling of T antigen, occurred predominantly in cells of the central nervous system. Integration of the transgene was mapped by in situ hybridization on metaphasic plaques in region B-C1 of chromosome 12 (where the twi locus was previously localized). Long-term cultures of cells with neural characteristics could be established readily from the brain of the transgenic mice.
Mol Biol Med 1989 Dec
PMID:Neurological disorder in transgenic mice that express the large T antigen of polyoma virus in the nervous system. 256 75

The activity of 5'-nucleotidase in cerebellum subcellular fractions after the administration of the convulsant 3-mercaptopropionic acid was studied. This membrane enzyme presented an increase in its activity in certain fractions containing nerve endings and microsomes (Mic20, Mic100) in seizure and postseizure periods. 5'-nucleotidase activity in nuclear and myelin fractions did not show differences between the control and treated fractions. On the other hand, a decreased activity in the crude mitochondrial fraction and in a nuclear subfraction was found. It is suggested that the changes in the enzyme activity in some cerebellum fractions might be related to structural alterations previously observed in this laboratory and with the anticonvulsant actions of adenosine.
Mol Chem Neuropathol 1989 Oct
PMID:A study of 5'-nucleotidase activity in subcellular fractions of rat cerebellum after the administration of the convulsant 3-mercaptopropionic acid. 256 15

The levels of preprosomatostatin (preproSS) mRNA, somatostatin-like immunoactivity (SS-LI) (also known as somatotropin-release inhibitory factor, or SRIF), glutamic acid decarboxylase (GAD) activity and GAD mRNA were determined in several brain regions of amygdaloid-kindled rats. SS mRNA and SS increased in the cortex and striatum, while only SS increased in the hippocampus. No changes were detected in either GAD activity or GAD mRNA in any brain region. The data suggest that somatostatin may be one of the factors involved in the chain of events leading to kindled seizures.
Brain Res Mol Brain Res 1989 May
PMID:Amygdaloid kindling of rats increases preprosomatostatin mRNA and somatostatin without affecting glutamic acid decarboxylase (GAD) mRNA or GAD. 256 84

In order to develop a rational clinical treatment for any pathological state, the molecular bases for that state must be understood. As simple and logical as that statement appears, it remains the major obstacle to effective treatment of the family of neurological disorders collectively called the epilepsies. Under the term, the epilepsies are grouped as several types of seizure processes that undoubtedly have multiple pathophysiological causes. Thus, the search to elucidate the molecular bases for the epilepsies has as one of its fundamental components the careful selection of an appropriate model system. The search for an "ideal" seizure model has essentially followed two paths. In the first, animals are rendered "epileptic" by artificial methods and then the pathophysiological, electrophysiological, and pharmacological changes are evaluated. In the second, animals are developed with a genetic predisposition to seizures and used to evaluate the molecular bases for the seizure-prone state. Work using both types of models have provided valuable information about the epileptic state. This review describes an epilepsy model developed using the second approach, namely, the Genetically Epilepsy-Prone Rat (GEPR). These animals represent a valuable model for the study of the inborn neurological defect that predisposes these animals to seizures. A brief description of the work done in several laboratories characterizing the model is presented. Finally, the value of the GEPR as a model for studying the pathophysiology of the epilepsies will be described.
Mol Chem Neuropathol 1989 Aug
PMID:The genetically epilepsy-prone rat. A valuable model for the study of the epilepsies. 257 May 85

The effects of deep prepyriform cortex (DPC) kindling on the amount of proenkephalin and prodynorphin mRNAs, Met5-enkephalin (ME) and dynorphin (DYN) in rat brain were examined. Animals received electrical stimulation of the DPC until two consecutive stage 2 seizures (S2) or stage 5 seizures (S5) were attained. The proenkephalin mRNA and ME contents in the entorhinal cortex were increased 24 h after S2 and also 5 min and 24 h post S5. In the hippocampus, the proenkephalin mRNA level was reduced 24 h after S2 but increased 5 min and 24 h after S5. Elevated hippocampal ME concentration was observed 24 h after S2 and S5. Similarly, the ME level in the frontal cortex was increased 24 h after S2 and S5 but the proenkephalin mRNA content was only elevated at S5. In the striatum, the proenkephalin mRNA level was slightly increased 24 h after S2 and S5, but no change in ME content was found. The amount of prodynorphin mRNA in the hippocampus was attenuated only at 24 h after S5, whereas DYN concentration was reduced 5 min after S5. No change in striatal DYN concentration was observed despite a slight elevation of prodynorphin mRNA 24 h post S2 and S5. Six weeks after the last seizure, no difference in ME and DYN was found between kindled and control animals. These findings indicate that the enkephalin-containing perforant pathway in the entorhinal cortex-hippocampal region is particularly sensitive to electrical stimulations applied to the DPC. Its role and importance in the development of kindling are discussed.
Brain Res Mol Brain Res 1989 Dec
PMID:Changes of proenkephalin and prodynorphin mRNAs and related peptides in rat brain during the development of deep prepyriform cortex kindling. 259 81

Recent findings suggest that steroids with sedative-hypnotic properties interact specifically with the gamma-aminobutyric acidA/benzodiazepine receptor-chloride ionophore complex (GBRC). They show positive heterotropic cooperativity by allosterically enhancing the binding of GABA agonists and the clinically useful benzodiazepines (BZs) to their respective recognition sites. These steroids have stringent structural requirements for activity at the GBRC, with the essential requirements for high potency being a 3 alpha-hydroxyl group and a 5 alpha-reduced A-ring. Some of these steroids are naturally occurring metabolites of progesterone and deoxycorticosterone and have nanomolar potencies as potentiators of chloride channel conductance. These 3 alpha-hydroxylated, 5 alpha-reduced steroids do not act through any known sites on the GBRC. Thus, the exact site and mechanism of action remain to be determined. Together with the observation that physiological levels of these metabolites are sufficient to influence the function of the GBRC, the evidence clearly suggests a role for these steroids in the normal regulation of brain excitability by potentiating the postsynaptic effects of gamma-aminobutyric acid (GABA). Pharmacological studies of the GBRC-active steroids show that they possess anxiolytic and anticonvulsant activities. The potential therapeutic application of these steroids in the treatment of mood disorders and catamenial exacerbation of seizures associated with the menstrual cycle is discussed. Collectively, the evidence from the studies of these steroids imply that another mechanism by which the endocrine system influences brain function has been identified. Its characterization will provide important insight into how steroids modulate brain excitability under normal and pathophysiological states.
Mol Neurobiol 1988
PMID:Steroid modulation of the GABA/benzodiazepine receptor-linked chloride ionophore. 285 77


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