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)

Neuroendocrine disturbances are among the significant problems associated with animal and human seizures. To investigate the mechanisms for these disturbances, we examined changes in the expression of vasopressin (VP) mRNA in the hypothalamic magnocellular neuroendocrine cells of rats after amygdala kindled seizures, a model for temporal lobe epilepsy. A prominent increase in VP mRNA was found in the supraoptic nucleus of kindled animals by one week after the last seizure which persisted for at least 4 months. The increase occurred bilaterally in the SON and remained unchanged despite the absence of further stimulation, seizures or change in body fluid homeostasis. Since the VP mRNA change after kindling correlated with the duration of afterdischarge but not the number of amygdala stimuli the change appears to be an effect of the seizure. This chronic increase in VP mRNA appears to reflect a change in neuroendocrine gene expression and may identify an important new mechanism of plasticity that contributes to the neuroendocrine disturbances accompanying epilepsy.
Brain Res Mol Brain Res 1994 Jul
PMID:Kindled seizures induce a long-term increase in vasopressin mRNA. 796 59

This study determined in temporal lobe epilepsy patients if there were correlations among hippocampal granule cell expression of neurotrophin mRNAs, aberrant supragranular mossy fiber sprouting, and neuron losses. Consecutive surgically resected hippocampi (n = 9) and comparison tissue from autopsies (n = 3) were studied for: 1. Granule cell mRNA levels using in situ hybridization for brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin-3 (NT-3); 2. neo-Timm supragranular mossy fiber sprouting; and 3. Ammon's horn neuron densities. Clinically, patients were classified into those with hippocampal sclerosis (HS; n = 7) and non-HS cases (i.e., mass lesions and autopsies; n = 5). Results showed that compared to non-HS cases, HS patients showed increased granule cell mRNA levels for BDNF, NGF, and NT-3 (p = 0.035, p = 0.04, p = 0.045 respectively; one-tail directional test). Moreover, granule cell BDNF mRNA levels correlated inversely with Ammon's horn neuron densities (p = 0.02) and correlated positively with greater supragranular mossy fiber sprouting (p = 0.02). NGF mRNA levels correlated inversely with Ammon's horn neuron densities (p = 0.02), and NT-3 mRNA levels correlated inversely with age at surgery (p = 0.04) and correlated positively with greater mossy fiber sprouting (p = 0.026). These results indicate in the chronically damaged human hippocampus that granule cells express neurotrophin mRNAs, and mRNA levels correlate with either hippocampal neuron losses or aberrant supragranular mossy fiber sprouting. These data support the hypothesis that in the epileptic human hippocampus, there may be pathophysiologic associations among mossy fiber synaptic plasticity, hippocampal neuron damage, and granule cell mRNA neurotrophin levels.
Mol Chem Neuropathol
PMID:Granule cell mRNA levels for BDNF, NGF, and NT-3 correlate with neuron losses or supragranular mossy fiber sprouting in the chronically damaged and epileptic human hippocampus. 913 29

A rat brain cDNA coding for ecto-(Ca,Mg)-apyrase activity was isolated using human CD39 cDNA and functionally expressed in COS-7 cells. The gene codes for a protein with high similarity to human (75% identity) and murine (90% identity) CD39. It is expressed in primary neurons and astrocytes in cell culture as well as in kidney, liver, muscle and spleen. Southern analysis of the mouse genome suggests that there may be a single copy of the ecto-apyrase gene. Interestingly, the human CD39 gene cytologically co-localizes with the susceptibility gene involved in human partial epilepsy with audiogenic symptoms; such a coincidence is consistent with reports on the deficiency of ecto-apyrase activity in the brains of humans with temporal lobe epilepsy and in those of mice with audiogenic seizures.
Brain Res Mol Brain Res 1997 Jul
PMID:Characterization of brain ecto-apyrase: evidence for only one ecto-apyrase (CD39) gene. 922 28

Systemic administration of kainic acid (KA), a glutamate receptor agonist, causes robust seizures and has been used as an excellent rodent model for human temporal lobe epilepsy. Recently, we have demonstrated that a single injection of KA increases the steady-state levels of proenkephalin (PENK) mRNA in the rat hippocampus for at least one year. However, the molecular mechanisms underlying this long-term increase in PENK mRNA levels have not been clearly defined. To determine the possible involvement of the Sp-1 transcription factors in this regulation, electrophoresis mobility-shift assays were used to study the expression of Sp-1 factors in the hippocampus after KA treatment. The results showed that there are long-lasting increases in Sp-1 DNA-binding activity. The Sp-1 DNA-binding complexes were only competed by the non-radioactive Sp-1 element and not by ENKCRE2, AP-1 or CRE elements, indicating the specificity of Sp-1 DNA-binding activity. Since the expression of Sp-1 parallels the time course of long-lasting increase in the expression of PENK mRNA and mossy fiber sprouting after KA treatment, we hypothesize that the increase in Sp-1 activity may be associated with the long-term changes in the plasticity of hippocampal function after KA-induced seizures.
Brain Res Mol Brain Res 1999 May 21
PMID:Long-term increase of Sp-1 transcription factors in the hippocampus after kainic acid treatment. 1035 Jun 46

The El mouse is an internationally registered animal model for hereditary temporal lobe epilepsy. When the mice receive weekly vestibular stimulation, e.g., 30 "tosses" 10-15 cm vertically, they start to convulse after 6-7 weeks on application of appropriate vestibular stimulation. The aim of this study was to explore the pathogenesis of the disease. By means of differential mRNA display we have screened five cDNAs which were upregulated in the brain of activated El mice given repeated vestibular stimulation. The differential expression of two (DD7/8 and DD8/24) cDNAs could be confirmed by Northern analyses. Sequence of the clones revealed that they were associated with mitochondrial respiratory enzymes, i.e., type 1 subunit of cytochrome c oxidase and a precursor of type 1 subunit of NADH dehydrogenase. The expression of these two genes was significantly increased in the El mice, which were activated by periodically repeated vestibular stimulation. The increased expression of these two genes may reflect increased demand for energy due to neuronal activation caused by repeated vestibular stimulation.
Brain Res Mol Brain Res 1999 Nov 10
PMID:Increased expression of mitochondrial respiratory enzymes in the brain of activated epilepsy-prone El mice. 1058 12

It has been demonstrated in animal models that chronic epilepsy is associated with increased excitability which may result from abnormal glutamatergic transmission involving altered properties of N-methyl-D-aspartate (NMDA) receptors. We have investigated whether human temporal lobe epilepsy is associated with changes in the NMDA receptor at the molecular level by assessing the relative expression of mRNAs of the different splice variants at the N-terminal (exon 5) and C-terminal (exon 21) position for the NMDAR1 subunit. Specimens of hippocampus and temporal lobe cortex from patients with refractory epilepsy were obtained during neurosurgical operations and analyzed by means of the reverse transcription reaction followed by polymerase chain reaction. Non-epileptic control specimens obtained at autopsy exhibited a relatively high level in expression of exon 5-lacking (hippocampus: 0.87; cortex: 0.81) and exon 21-containing (hippocampus: 0.95; cortex: 0.93) transcripts. The ratio for these alternatively spliced transcripts was not significantly changed in epileptic hippocampal and cortical tissues relative to the corresponding non-epileptic samples. These results did not support a potential role for NMDAR1 splice variants in the pathophysiology of epilepsy.
Brain Res Mol Brain Res 2000 Mar 29
PMID:Alternative splicing of the NMDAR1 glutamate receptor subunit in human temporal lobe epilepsy. 1076 14

We have analyzed whether the expression of connexin genes is altered in the hippocampus of kindled and kainate-treated rats, i.e., animal models of human temporal lobe epilepsy. We have tested this hypothesis by analyzing mRNA, protein abundance and cellular location of connexins (Cx) 43, 36, 32 and 30. The expression of glial fibrillary acid protein and mRNA was also monitored both in kainate-treated and kindled rats, in order to take into account reactive gliosis under these conditions. We found significantly increased expression of GFAP mRNA (100%) and protein (178%) in kainate-treated rats 4 weeks after kainate application, whereas in kindled rats only moderate increases of GFAP mRNA and protein were detected 2-3 weeks (group 2) or 4-6 weeks (group 1) after the last stage 5 induced seizure. Under gliotic conditions, connexins 43 and 30 mRNA or protein expression in astrocytes of kainate-treated rats were nearly unaffected. Cx36 mRNA expression (presumably in neurons) was significantly reduced (44%), whereas abundance of Cx36 protein was only slightly reduced. In both groups of kindled rats, Cx30 and Cx43 mRNA or protein expression were either slightly decreased or unchanged. Again, Cx36 mRNA and protein expression were reduced by about half in group 2. Immunofluorescence analysis of Cx43, Cx36 and Cx30 expression revealed that 4 weeks after the last kainate administration or kindling, cellular localization of these connexins was indistinguishable from control animals.
Brain Res Mol Brain Res 2000 Nov 10
PMID:Expression of connexin genes in hippocampus of kainate-treated and kindled rats under conditions of experimental epilepsy. 1107 94

GABA(B) receptors act to inhibit neurotransmitter release from presynaptic terminals, and mediate the late inhibitory postsynaptic potential. Studies of GABA(B) receptor function in rodent models of temporal lobe epilepsy (TLE) suggest that GABA(B) receptor expression and/or function may be perturbed. GABA(B(1)) mRNA levels were investigated in 10 hippocampal resection samples obtained at surgery from intractable hippocampal sclerosis (HS) associated TLE patients and five neurologically normal post-mortem (PM) control samples. In situ hybridisation with a 35S-dATP-labelled oligonucleotide was carried out to measure mRNA levels, along with three-dimensional cell counting, for assessment of neuronal density in hippocampal subregions. GABA(B(1)) mRNA was significantly up-regulated in the subiculum of HS samples as compared with PM controls. When adjusted for the characteristic neuronal density changes observed in HS, GABA(B(1)) mRNA was significantly up-regulated in CA1, hilus and dentate gyrus granule cell layer of HS samples as compared with PM controls. The possibility of increased GABA(B(1)) expression suggests that changes in GABA(B) receptor mechanisms may be involved in the pathogenesis of human HS-associated TLE.
Brain Res Mol Brain Res 2001 Jan 31
PMID:GABA(B(1)) mRNA expression in hippocampal sclerosis associated with human temporal lobe epilepsy. 1116 75

'Kindling' is a phenomenon of epileptogenesis, which has been widely used as an experimental model of temporal lobe epilepsy. In the present study, we have examined the contribution of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) glutamate receptors and their subunits (GluR-A, -B, -C and -D) to the acquisition and maintenance of the kindled state in the pentylenetetrazole (PTZ)-induced 'kindling' mouse model, by using quantitative autoradiography and in situ hybridization. Region-specific increases in [3H]AMPA binding were seen in kindled animals in the CA3 region of hippocampus and in the temporal cortex 1 week after the last PTZ injection. At the same time, a significant decrease in the level of transcripts encoding the GluR-B and -C subunits was detected in the hippocampal CA1 region and dentate gyrus, suggestive of a higher proportion of Ca(2+)-permeable AMPA receptors in these neurons. These changes did not persist 1 month after establishment of kindling, indicating a transient role of AMPA receptors in the acquisition of the kindled state. At 1 month after the last PTZ injection, an upregulation in [3H]AMPA binding appeared in the motor cortex and the basal ganglia of kindled animals, which is consistent with electrophysiological data showing hyperexcitability in the cortex of the PTZ-kindled animals at that time. Interestingly, an increase in mRNA for the GluR-B subunit appeared in the outer layers of motor and somatosensory cortices of the kindled animals 1 month after acquisition of the kindled state, possibly as part of a gene-regulated, compensatory mechanism against seizure susceptibility, since this change should give rise to a higher proportion of Ca(2+)-impermeable AMPA receptors. These results support the evidence of a transient role of hippocampal AMPA receptors in the acquisition of the 'kindling' phenomenon and they also suggest an involvement of AMPA receptors in the maintenance of kindled state at least in two brain areas, cortex and basal ganglia.
Brain Res Mol Brain Res 2001 Nov 01
PMID:Changes in AMPA receptor binding and subunit messenger RNA expression in hippocampus and cortex in the pentylenetetrazole-induced 'kindling' model of epilepsy. 1168 74

This study investigated whether repeated ictal single-photon emission tomography (SPET) is helpful in the localization of epileptogenic zones and whether it can provide information confirming that an area of increased perfusion is really the culprit epileptogenic lesion. Fifty-four repeated ictal SPET studies were performed in 24 patients with ambiguous or unexpected findings on the first ictal SPET study. These patients were enrolled from among 502 patients with intractable epilepsy in whom pre-operative localization of epileptogenic zones was attempted with a view to possible surgical resection. Video monitoring of ictal behaviour and EEGs was performed in all patients. Repeated ictal SPET was performed using technetium-99m hexamethylpropylene amine oxime (HMPAO) when there was no prominently hyperperfused area or when unexpected findings were obtained during the first study. Two ictal SPET studies were performed in 19 patients, three studies in four patients and four studies in one patient. The average delay between ictal onset and injection was 28 s for the first study and 22 s for the second, third and fourth studies. Using interictal SPET, ictal-interictal subtraction images were acquired and co-registered with the population magnetic resonance imaging (MRI) template. Invasive study and surgery were performed in 18 patients, and in these cases the surgical outcome was known. In the other six patients, epileptogenic foci were determined using MRI, positron emission tomography (PET) and ictal EEG findings. Two patients were found to have mesial temporal lobe epilepsy, two lateral temporal lobe epilepsy, eight frontal lobe epilepsy, three parietal lobe epilepsy and one occipital lobe epilepsy. The other eight had multifocal epilepsy. The first study was normal in 12 patients (group I) and indicated certain zones to be epileptogenic in the other 12 (group II). Among group I, the correct epileptogenic zone or lateralization was revealed at the repeated study in nine patients, while in the other three it was not. Among group II, six patients showed the same results at the second study, thus confirming that the initially identified zones were of epileptogenic significance. In the other six patients, different areas were identified on the first and second studies, and repeated ictal SPET corroborated multifocality of the ictal EEG findings in five. These results indicate that repeated ictal SPET is useful because it can yield new or additional information about the epileptogenic zones and can confirm that a region of interest is an epileptogenic zone or that the epilepsy is of multifocal origin.
Eur J Nucl Med Mol Imaging 2002 May
PMID:The usefulness of repeated ictal SPET for the localization of epileptogenic zones in intractable epilepsy. 1197 98


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