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

Because of the many anatomical and functional links to the limbic system, the neuroendocrine system is often affected by limbic disturbances. Limbic seizures in humans and animals alter neuroendocrine function and hormone levels. We have shown that in an animal model for partial seizures, the amygdala kindled rat, plasma vasopressin levels are elevated and a sustained increase in vasopressin (VP) mRNA follows stage 5 kindled seizures. In the present experiments we sought to determine when during the course of amygdala kindling the VP mRNA increase occurs and whether specific anatomical pathways mediate this increase. Animals kindled to early seizure stages (stages 1, 2 or 3) had no consistent increase in VP mRNA in the supraoptic nucleus (SON) while animals kindled to generalized seizures, stages 4 or 5, invariably had increased VP mRNA relative to controls. Electrical kindling to stage 5 seizures from two other brain sites, the dorsal hippocampus and the anterior olfactory nucleus, consistently resulted in a significant increase in VP mRNA one week after completing kindling. In all experiments the increase in VP mRNA in the SON showed no differences related to the side or proximity of the electrodes used for kindling. Measures of water balance did not change following kindling. These results indicate that kindled seizure generalization is a prerequisite for the long-term increase in VP mRNA. Furthermore, the VP mRNA increase appears to involve polysynaptic pathways accessible from different limbic kindling sites. These studies support the hypothesis that changes in mRNA regulation may contribute to the neuroendocrine pathophysiology accompanying limbic seizures.
Brain Res Mol Brain Res 1994 Oct
PMID:Vasopressin mRNA changes during kindling: the effects of kindling site and stage. 785 58

Intrahippocampal injection of the endogenous excitotoxin quinolinic acid (QUIN) induces seizures together with local, delayed neurodegeneration in specific cell layers. In situ hybridization histochemistry was used to study the spatio-temporal pattern of expression of neurotrophins (NTFs) after this treatment. As in other excitatory paradigms, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) mRNA levels increased dramatically and transiently in dentate gyrus after the administration of 120 nmol of QUIN to the left hippocampus. BDNF, but not NGF, mRNA also increased in the hippocampal pyramidal cell layer, mainly in the CA1 field. Neurotrophin-3 (NT3) mRNA levels decreased in dentate gyrus, practically disappeared around 12 h after the insult and returned to basal levels four days later. A very different pattern of expression of NTFs was found locally: (a) upregulation of NGF and BDNF mRNAs expression was prevented in a spherical region of 1-2 mm diameter around the injection site, (b) a delayed increase in NT3 mRNA levels, beginning at 12 h and lasting for at least 4 days after the administration of QUIN, was found in the same region, in cell layers showing neurodegeneration. Pretreatment with the non-competitive NMDA antagonist MK-801 (2 mg/kg, 30 min before the insult), partially blocked the increase in both BDNF and NGF mRNAs, as well as the decrease in NT3, in the contralateral hippocampus. However, this treatment did not prevent the QUIN-induced local downregulation of NGF and BDNF. Treatment with the AMPA/kainate antagonist NBQX (30 mg/kg, 15 and 5 min before, and 10 min after the insult) did not influence the effect of QUIN upon NGF or BDNF mRNA levels, although it partially prevented the hippocampal contralateral decrease in NT3 mRNA. In conclusion, the present study strongly supports previous work concerning different regulation of BDNF/NGF respect to NT3 in seizure inducing paradigms. Moreover, the different and to some extent opposite regulation of NTFs in the hippocampal region contiguous to the injection site, respect to the remaining hippocampus, suggests a differential regulation of NTFs in QUIN-induced neurodegenerative and seizural processes. Finally, our pharmacological data, (i) show that the upregulation of NGF and BDNF mRNAs, indirectly induced by QUIN, is not mediated by AMPA receptors, and (ii) suggest other effects for QUIN, apart from the stimulation of NMDA receptors.
Brain Res Mol Brain Res 1994 Oct
PMID:Differential regulation of the expression of nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 mRNAs in adult rat brain after intrahippocampal injection of quinolinic acid. 785 71

Previous studies have shown that neuropeptide mRNA expression is altered in the dentate gyrus, and pyriform, entorhinal and perirhinal cortices following amygdala kindling. However, because rats were kindled every day and some mRNA alterations last longer than 24 h, a true measure of the alterations induced by a single seizure was confounded by the previous day's seizure. To circumvent this problem, rats were fully kindled, had six days without stimulation, and then were given one more seizure. Rats were sacrificed either 4 h, 24 h or 4 days after this last seizure. The levels of mRNAs for TRH, NPY and ENK were measured in the dentate gyrus and limbic cortices. Four hours after a seizure, TRH and NPY mRNAs were maximally increased in the dentate gyrus granule layer, but returned to baseline levels by 24 h. In contrast, 4 h after a seizure, TRH and NPY mRNAs were not, or only slightly, increased in the pyriform, entorhinal and perirhinal cortices, but significantly elevated 24 h after a seizure. ENK mRNA was increased both 4 and 24 h after a seizure in the pyriform, entorhinal and perirhinal cortices but showed no increases in the dentate gyrus at any time. By 4 days, peptide mRNA levels returned to baseline, except for ENK mRNA in the pyriform cortex. These results demonstrate a non-uniform and complex pattern of peptide mRNA expression following an amygdala kindled seizure. They further suggest that regional and time course differences in gene transcription and expression may be important factors in understanding both the transient, adaptive anticonvulsant and longer lasting proconvulsant effects of these neuropeptides.
Brain Res Mol Brain Res 1994 Nov
PMID:Differential regional and time course increases in thyrotropin-releasing hormone, neuropeptide Y and enkephalin mRNAs following an amygdala kindled seizure. 787 57

The present study investigated the mechanisms of gastric antisecretory action of pentylenetetrazol (PTZ) in pylorus-ligated rats. Pretreatment with indomethacin, phentolamine, propranolol, 6-hydroxydopamine, flunarizine and nifedipine, which were reported to antagonize seizures induced by PTZ, did not influence the gastric antisecretory action of PTZ. In contrast, pentobarbital and phenobarbital reverse the action of PTZ. These results suggest that prostaglandins production, adrenoceptors and calcium entry are not involved in the gastric antisecretory action of PTZ, and that the GABAA receptor complex plays an important role in the action induced by PTZ.
Res Commun Mol Pathol Pharmacol 1994 Nov
PMID:Mechanisms of gastric antisecretory action of pentylenetetrazol in rats. 788 72

Neurochemical observations on cortical biopsies form 48 patients under surgical treatment for pharmacoresistant partial epilepsy showed a 70-80% increase in glutamate concentration when expressed in relation to neuron specific enolase. Intraperitoneal administration of one of its receptor agonists, kainic acid (KA), to the rat led to increased epileptogenic activity of the limbic type in a dose-dependent fashion. The KA injection also led to a neuronal cell death and a gliosis, closely correlated to the extent of seizure activity. In biopsies from human epileptogenic cortex, the concentration of neuron specific enolase correlated inversely to that of glial fibrillary acidic protein, a marker for astrocytic glial cells. Stimulation of the KA receptor decreased the extent of phosphorylation of the largest subunit of neurofilaments (NF-H) that have consequences for structural stability and axonal transport. Phosphorylated NF-H decreased also in human epileptic cortex, indicating either an overactivity of excitatory neurotransmitters or a loss of axonal compartments.
Mol Neurobiol
PMID:Excitotoxicity. Experimental correlates to human epilepsy. 788 4

Previous studies have shown that song presentation results in a rapid rise in mRNA levels for the ZENK gene (the avian homologue of zif-268, Egr-1, NGFI-A, and Krox-24) in specific parts of the songbird forbrain. Metrazole-induced seizures also cause an increase in ZENK mRNA, even more widely throughout the telencephalon. Surprisingly, however, little or no ZENK induction by either stimulus was observed in several forebrain areas involved in auditory processing and song production. To learn whether this pattern of regulation is specific to ZENK, we examined the response of another 'immediate-early' gene, c-jun. Here we first describe the identification, cloning and sequence analysis of a canary cDNA encoding c-jun. Then, by in situ hybridization we show that c-jun is also induced by song or seizure, and in a pattern mostly similar to ZENK. As with ZENK, no induction of c-jun is observed in the androgen receptor-containing song nuclei or within the primary thalamo-recipient auditory area of the forebrain. Thus common immediate early gene responses appear to be selectively uncoupled from physiological activation in these specific forebrain regions, which are also characterized by tight developmental, hormonal and seasonal regulation.
Brain Res Mol Brain Res 1994 Dec
PMID:Immediate-early gene responses in the avian song control system: cloning and expression analysis of the canary c-jun cDNA. 789 14

Within the hippocampus, stimulus-transcriptional coupling plays an important role in post-seizure neuronal adaptation, post-ischemic cell death and the induction of long-term potentiation. To identify additional mediators of hippocampal transcriptional responses a targeted approach was developed and used to characterize the spectrum of nuclear hormone receptors expressed within this brain region. cDNAs encoding the DNA-binding domains of six different members of the nuclear hormone receptor superfamily were isolated. A majority were identical or closely related to receptors known to be expressed within the hippocampus. Two additional isolates, HZF-2 and HZF-3, encode the DNA-binding domain of novel members of the nuclear hormone receptor superfamily.
Brain Res Mol Brain Res 1994 May
PMID:Expression of nuclear hormone receptors within the rat hippocampus: identification of novel orphan receptors. 791 60

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

A unilateral hypoxia-ischaemia (HI) 21-day-old rat preparation was used to assess the effects of HI on the expression of the immediate-early gene proteins (IEGPs) c-Fos/FRAs, Fos B, c-Jun, Jun B, Jun D, Krox 20, Krox 24, and on the mRNA for the neurotrophic factor, brain-derived neurotrophic factor (BDNF). Moderate HI (15 min hypoxia) produced delayed, selective neuronal death and was associated with a rapid induction of c-Fos, Fos B, Jun B, Jun D, and c-Jun proteins, but not Krox 20 protein or BDNF mRNA, in neurons on the side of HI and also a delayed expression of c-Jun (and to a lesser extent c-Fos/FRA's and Fos B) 24-48 h after HI in neurons that underwent delayed neuronal death. Krox 24 showed an initial induction followed by a long-lasting suppression of its expression in regions undergoing cell loss. Severe HI (60 min hypoxia) resulted in seizures and rapid neuronal loss and infarction (necrotic cell death) on the side of HI, and was associated with early induction of c-Fos, Fos B, c-Jun, Jun B, Jun D, Krox 20 and Krox 24 protein and BDNF mRNA in neurons on the non-ligated side of the brain. Fos, c-Jun, Jun B, Jun D and Krox 24, but not Krox 20, Fos B, or BDNF mRNA, were also induced in non-nerve cells on the damaged side of the brain after both moderate and severe HI, and many of these cells appeared to be dividing. Thus, moderate HI induces IEGP's in neurons and non-nerve cells in damaged regions, whereas severe HI induces IEGP's and BDNF in non-damaged regions. c-Jun (and to a lesser extent c-Fos/FRA's) showed a prolonged expression in neurons undergoing delayed, but not necrotic, cell death suggesting that they may be involved in the biochemical cascade that causes selective delayed neuronal death. BDNF was not induced by HI, and therefore, does not appear to play an endogenous neuroprotective role in the CNS.
Brain Res Mol Brain Res 1994 Aug
PMID:Immediate-early gene protein expression in neurons undergoing delayed death, but not necrosis, following hypoxic-ischaemic injury to the young rat brain. 798 48

The mRNA levels of four immediate early genes (IEG) were measured in rat brain regions 60 min after administration of pilocarpine (30 mg/kg) to lithium-treated (3 mmol/kg) rats, during generalized convulsive status epilepticus. Northern blots demonstrated induction of the genes in the order of c-fos = jun-B > c-jun > jun-D with large increases in the cerebral cortex, hippocampus, and striatum, a smaller increase in the cerebellum, and less in the brainstem. The mRNA levels of these four IEG were measured in rat cerebral cortex and hippocampus at several times after administration of the cholinergic agonist pilocarpine (5 or 30 mg/kg) with or without lithium pretreatment (3 mmol/kg, 16 h prior, or chronic 4 week dietary administration). Treatment with pilocarpine (30 mg/kg) alone increased mRNA levels in the order of c-fos > jun-B > c-jun but did not change the jun-D mRNA level, and maximal c-fos and jun-B mRNA levels occurred earlier (30 min) in the cortex than in the hippocampus. Treatment with the lower dose of pilocarpine (5 mg/kg) alone caused only small increases in c-fos and jun-B mRNA levels and these responses were unaffected by lithium pretreatment. Lithium pretreatment potentiated IEG expression induced by 30 mg/kg pilocarpine, likely as a result of the seizures caused by this combination of drugs because pretreatment with anticonvulsants (diazepam or MK-801) blocked seizures and the enhanced IEG mRNA levels. The mRNA levels were increased during seizures in the order of c-fos > jun-B > c-jun > jun-D in the hippocampus and jun-B > c-fos > c-jun > jun-D in the cortex, and were increased for a longer duration as well as to a greater extent than after administration of pilocarpine alone. Administration of pilocarpine (30 mg/kg) to rats treated chronically with lithium caused increases similar to those measured with acute lithium pretreatment. Thus the induction of IEG by cholinergic stimulation varied with dose, time, and brain region, and unique responses were observed for each of the IEG. Lithium pretreatment did not impair IEG expression induced by the lower dose of pilocarpine and greatly enhanced expression of IEG after administration of the higher dose of pilocarpine concomitant with seizure activity.
Brain Res Mol Brain Res 1994 Aug
PMID:Distinctive rat brain immediate early gene responses to seizures induced by lithium plus pilocarpine. 798 56


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>