Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In situ hybridization histochemistry, Northern blot analysis and immunohistochemistry were used to examine tyrosine hydroxylase (TH) mRNA concentrations and immunoreactivity in the locus coeruleus and cerebellum of the tottering (tg/tg), leaner (tgla/tgla), compound heterozygous (tg/tgla) and wild type control (+/+) mice, bred on a C57BL/6J background. Cerebellar Purkinje neurons, long considered to be GABAergic, showed high levels of TH mRNA in the caudal vermis and the lateral hemispheres of the cerebellum of tg/tg, tg/tgla, and tgla/tgla mice. Analysis of grain density over individual Purkinje cells showed significantly greater concentrations of TH mRNA in tg/tg, tg/tgla, and tgla/tgla mice as compared to +/+ wild type control mice. Comparison of adult (greater than or equal to 2 months) and young, pre-seizure (less than or equal to 3 weeks) mutant mice showed Purkinje cells densely labelled for TH mRNA at both ages, suggesting that TH gene expression in Purkinje cells is independent of the onset of seizures. Northern blot analysis confirmed the findings from the in situ hybridization studies, demonstrating a single band identical to TH mRNA. Immunohistochemistry confirmed the presence of TH protein in Purkinje cells of the caudal vermis and the lateral hemispheres of the cerebellum in both control and mutant mice. Quantitation of mRNA for TH and the coexisting neuropeptide, galanin, in the locus coeruleus detected no significant differences between adult tg/tg, tg/tgla and +/+ control mice. The present findings demonstrate that the classically GABAergic Purkinje cells in the cerebellum express low levels of TH, and that the mutant tottering and leaner strains of mice express extremely high levels of mRNA and protein for TH.
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PMID:Expression of tyrosine hydroxylase in cerebellar Purkinje neurons of the mutant tottering and leaner mouse. 127 53

Galanin (2000, 1000 ng) administered into the lateral brain ventricle decreased the severity of picrotoxin-kindled convulsions in rats. The bilateral injection (200, 100 and 50 ng) of galanin into the hippocampus also evoked an anticonvulsive effect. When administered into the caudate nuclei or substantia nigra reticulata, galanin exerted anticonvulsive action only in a high dose (200 ng), whereas in the nucleus accumbens it did so in a low dose (50 ng). When administered into the ventral tegmental area in a dose of 50, 100 or 200 ng galanin failed to reduce the manifestations of picrotoxin-kindled seizures.
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PMID:Anticonvulsive effects of galanin administered into the central nervous system upon the picrotoxin-kindled seizure syndrome in rats. 138 26

Endocrine and reproductive alterations are frequently reported to occur in women with temporal lobe epilepsy as well as in female rats in different experimental models of limbic seizures. We have recently observed that rats with structural damage of limbic structures induced by sustained convulsions triggered by systemic administration of pilocarpine develop spontaneous seizures after a mean latency of 15 days. In order to investigate the possible substrate of endocrine alterations in epilepsy, changes of the gonadotropin-releasing hormone (GnRH) and the neuropeptide galanin (GAL) were studied in the hypothalamus of epileptic female rats after pilocarpine treatment. Female rats injected with pilocarpine (320-350 mg/kg, i.p.) and control cases injected with saline were killed 10-20 h, 10-15 or 60-90 days following treatment. In some of these animals colchicine was injected in the lateral cerebral ventricle 24 h before death. GnRH immunopositivity was observed in the hypothalamus in neuronal cell bodies, fibers and punctate elements of both epileptic and control cases. A striking reduction of the density of GnRH-immunoreactive fibers and puncta was observed in the hypothalamus of the epileptic female rats killed 10-15 or 60-90 days following pilocarpine administration. No significant differences were observed in the number and size of GAL-immunoreactive perikarya of epileptic and control cases. The present findings suggest that a substantial rearrangement of GnRH-containing efferents, and in particular a loss of their terminal branches, occurs in the epileptic rat brain. Comparable regressive changes could account for alterations in endocrine and reproductive functions observed in temporal lobe epilepsy.
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PMID:Epilepsy and hormonal regulation: the patterns of GnRH and galanin immunoreactivity in the hypothalamus of epileptic female rats. 768 Oct 3

In this work polyfunctional peripheral (pancreas) and central effects of galanin 1-29 (gal.) were reviewed. In hypothalamus gal. exerts neuroendocrine effects through modulation of secretion of principal hormones of hypophysis, co-localized with acetylcholine in some brain structures including hippocampus. Gal. influences behaviour and memory. Newest hypotheses of T. Hokfelt and J. N. Crawely [correction of G. Crowly] on the involvement of gal. to pathogenesis of in Alzheimer disease and possibilities of its clinical antiamnestic utility are discussed. Our own data indicates antiseizure effect of gal. in the model of febrile convulsions in children--hyperthermia induced seizures in neonatal rats in the age from 5 to 13 days. Systemic intraperitoneal administration of gal. was effective in certain age--7-11 days of postnatal period--in preventing hyperthermia induced seizures: in increased by 2-3 times latency of minimal seizures and clonic-tonic generalized seizures. In adults rats gal. showed antiseizure action when administered intranasal in the model of pentilenetetrazol seizures (modified test with repeated administration of subthreshold doses). Modern data on structure and function of galanin, its chimeric analogs and galanin receptors receptors are discussed.
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PMID:[The neuropeptide galanin and the seizure reactions of the developing brain]. 923 5

We examined the role of hippocampal galanin in an animal model of status epilepticus (SE). Control rats showed abundant galanin-immunoreactive (Gal-IR) fibers in the dentate hilus, whereas no Gal-IR neurons were observed. Three hours after the onset of self-sustaining SE (SSSE), induced either by intermittent stimulation of the perforant path for 30 min (PPS) or by injection of lithium and pilocarpine, Gal-IR fibers disappeared in the hilus and remained absent for up to 1 week afterward. Twelve hours after the induction of SE by PPS or 3 hr after pilocarpine administration, Gal-IR neurons appeared in the hilus; these neurons increased in number after 1 d and gradually declined 3 and 7 d later. Galanin concentration in the hippocampus, measured by ELISA, significantly decreased on the plateau of SSSE and increased 24 hr after PPS. Galanin (0.05 nmol) injected into the hilus prevented the induction of SSSE, and 0.5 nmol of galanin stopped established SSSE. These effects were attenuated by galanin receptor antagonists (M35 > M40 >/= M15). 2-Ala-galanin (5 nmol), a putative agonist of galanin type 2 receptors, prevented but was unable to stop SSSE. M35 facilitated the development of SSSE when given before PPS. We suggest that hippocampal galanin acts as an endogenous anticonvulsant via galanin receptors. SE-induced galanin depletion in the hippocampus may contribute to the maintenance of seizure activity, whereas the increase of galanin concentration and the appearance of galanin-immunoreactive neurons may favor the cessation of SSSE. The seizure-protecting action of galanin SSSE opens new perspectives in the treatment of SE.
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PMID:Galanin modulation of seizures and seizure modulation of hippocampal galanin in animal models of status epilepticus. 982 61

Neuropeptides: corticotropin releasing factor (CRF), neuropeptide Y (NPY) and somatostatin (STS) have been associated with depression and anxiety, while neurotensin (NT), calcitonin gene-related peptide (CGRP) and tachykinins [neurokinin A (NKA) and substance P (SP)] are presumed to also play a role in the function of the dopaminergic system. Moreover, investigations in the past decade have shown that psychotomimetics and antipsychotic drugs as well as lithium affect brain synthesis, tissue concentrations, and release of some neuropeptides. In view of the above, experiments were carried out to explore whether changes in neuropeptides constitute one of the mechanisms of action of electroconvulsive treatment (ECT). Human cerebrospinal fluid (CSF) was studied before and after ECT, and brains from healthy and models of depression rats were investigated in electroconvulsive stimuli (ECS)-treated and sham-treated animals. The major findings were that a series of ECTs, in parallel to clinical recovery, increased CSF concentrations of NPY-like immunoreactivity (-LI), STS-LI, and CRF-LI, and in one study endothelin-LI. A series of ECS, but not a single treatment, reproducibly elevated concentrations of NPY-LI, NKA-LI, and STS-LI--but not NT-LI, SP-LI, galanin-LI, or CGRP-LI--in hippocampus, frontal cortex, and occipital cortex. No changes were measured in other regions, e.g., striatum. NPY and STS mRNAs were also increased indicating that ECS affects peptide synthesis. Generalized seizures induced by, e.g., kainic acid or pentylenetetrazole, had similar effects on neuropeptides. The changes persisted for at least 1 week after the last treatment. Pretreatment with compounds reducing seizures, such as benzodiazepines and MK-801; had no effect on magnitude of neuropeptide changes although the seizure duration was decreased by > 50%. On the basis of these findings, it is suggested that neuropeptides are involved in ECT's mechanisms of action. Since ECT is therapeutically efficient in both schizophrenia and depression and, taking into account that antipsychotic drugs and psychotomimetics as well as lithium selectively affect some neuropeptides, it is hypothesized that distinct combinations of neuropeptide and monoamine changes in selected neuronal populations constitute the underpinnings of ECT's effects on specific disease symptoms, conceivably independent of diagnosis.
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PMID:Neuropeptides and electroconvulsive treatment. 1018 19

There has been direct evidence of gamma-aminobutyric acidA receptor modification during status epilepticus. Neuropeptides galanin and neuropeptide Y were demonstrated to play a role in terminating status epilepticus. Many of the CA3 pyramidal neurons destined to die as a consequence of status epilepticus were demonstrated to diminish expression of the GluR2 subunit of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors. It was demonstrated that the pattern of cell loss due to status epilepticus is distinct in immature pups compared with adult rats. The genetic basis for susceptibility to neuronal loss during status epilepticus was described. There was increasing evidence of unique receptors and ion channels in the epileptic brain. The molecular studies of epileptic gamma-aminobutyric acidA receptors present on dentate granule cells of rats with temporal lobe epilepsy revealed altered gene and receptor expression before onset of recurrent spontaneous seizures. They also revealed insertion of new gamma-aminobutyric acidA receptors in the inhibitory synapses present on soma and proximal dendrites of dentate granule cells.
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PMID:Status epilepticus in epileptogenesis. 1022 52

Previous studies have shown that the expression of the neuropeptide galanin in the hippocampus is altered by seizures and that exogenous administration of galanin into the hippocampus attenuates seizure severity. To address the role of endogenous galanin in modulation of hippocampal excitability and its possible role in seizure mechanisms, we studied two types of transgenic mice: mice with a targeted disruption of the galanin gene (GalKO) and mice that overexpress the galanin gene under a dopamine-beta-hydroxylase promoter (GalOE). GalKO mice showed increased propensity to develop status epilepticus after perforant path stimulation or systemic kainic acid, as well as greater severity of pentylenetetrazol-induced convulsions. By contrast, GalOE mice had increased resistance to seizure induction in all three models. Physiological tests of hippocampal excitability revealed enhanced perforant path-dentate gyrus long-term potentiation (LTP) in GalKO and reduced LTP in GalOE. GalKO showed increased duration of afterdischarge (AD) evoked from the dentate gyrus by perforant path simulation, whereas GalOE had increased threshold for AD induction. Depolarization-induced glutamate release from hippocampal slices was greater in GalKO and lower in GalOE, suggesting that alterations of physiological and seizure responses in galanin transgenic animals may be mediated through modulation of glutamate release. Our data provide further evidence that hippocampal galanin acts as an endogenous anticonvulsant and suggest that genetically induced changes in galanin expression modulate both hippocampal excitability and predisposition to epileptic seizures.
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PMID:Modulation of hippocampal excitability and seizures by galanin. 1093 78

Megencephaly, enlarged brain, is a major sign in several human neurological diseases. The mouse model for megencephaly (mceph/mceph) has an enlarged brain, presumably due to brain cell hypertrophy, and exhibits neurological and motor disturbances with seizure-like activity, as well as disturbances in the insulin-like growth factor system. Here, we report that expression of the neuropeptides cholecystokinin, enkephalin, galanin and neuropeptide Y is dramatically changed in mceph/mceph brains compared to wild type, as revealed by in situ hybridization and immunohistochemistry. The changes were confined to discrete brain regions and occurred in a parallel fashion for peptides and their transcripts. For cholecystokinin, mceph/mceph brains had region-specific up- and down-regulations in several layers of the hippocampal formation and increased levels in, especially ventral, cortical regions. Enkephalin messenger RNA expression was up-regulated in the dentate gyrus granular layer and in ventral cortices, but down-regulated in the CA1 pyramidal layer. Enkephalin-like immunoreactivity was elevated in mossy fibers of the hippocampus and the ventral cortices. Galanin expression was increased in several layers and interneurons of the hippocampal formation, as well as in ventral cortices. Galanin-like immunoreactivity was reduced in nerve terminals in the forebrain. Neuropeptide Y expression was increased in the hippocampal formation and ventral cortices. Whether the mainly increased peptide levels contribute to the excessive growth of the brain or represent a consequence of this growth and/or of the neurological and motor disturbances remains to be elucidated.
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PMID:Expression of cholecystokinin, enkephalin, galanin and neuropeptide Y is markedly changed in the brain of the megencephaly mouse. 1100 68

The neuropeptide galanin has been shown to suppress epileptic seizures. In cortical and hippocampal areas, galanin is normally mainly expressed in noradrenergic afferents. We have generated a mouse overexpressing galanin in neurons under the platelet-derived growth factor B promoter. RIA and HPLC analysis revealed up to 8-fold higher levels of galanin in transgenic as compared with wild-type mice. Ectopic galanin overexpression was detected especially in dentate granule cells and hippocampal and cortical pyramidal neurons. Galanin-overexpressing mice showed retardation of seizure generalization during hippocampal kindling, a model for human complex partial epilepsy. The high levels of galanin in mossy fibers found in the transgenic mice were further increased after seizures. Frequency facilitation of field excitatory postsynaptic potentials, a form of short-term synaptic plasticity assessed in hippocampal slices, was reduced in mossy fiber-CA3 cell synapses of galanin-overexpressing mice, indicating suppressed glutamate release. This effect was reversed by application of the putative galanin receptor antagonist M35. These data provide evidence that ectopically overexpressed galanin can be released and dampen the development of epilepsy by means of receptor-mediated action, at least partly by reducing glutamate release from mossy fibers.
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PMID:Suppressed kindling epileptogenesis in mice with ectopic overexpression of galanin. 1169 49


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