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)

We studied the effects of modification of duration of seizures induced by electroconvulsive stimuli (ECS) on the changes in concentration of neuropeptide Y (NPY), neurokinin A (NKA), substance P (SP) and neurotensin (NT)-like immunoreactivity (-LI) in specific rat brain regions. Rats were divided into groups pretreated with saline, indomethacin, flurbiprofen or diazepam prior to either six sham ECSs or six ECSs. After sacrifice by focused microwave irradiation, brains were dissected into frontal cortex, occipital cortex, striatum, hippocampus, pituitary and hypothalamic sections. Peptides were extracted and measured in extract aliquots by specific radioimmunoassays. Repeated ECS increased NPY-LI and NKA-LI in the hippocampus and the occipital cortex. No effect on SP-LI or NT-LI was found. Indomethacin and flurbiprofen had no effect on the tonic seizure time following ECS, and they did not affect the ECS-induced alterations of the brain peptides. Diazepam pretreatment decreased the tonic seizure time following ECS in a dose-dependent manner. However, diazepam did not modify the ECS-induced increase in NPY-LI and NKA-LI concentrations. The results firmly establish that ECS leads to specific peptide increases in discrete rat brain regions and raise the possibility that such changes may not entirely be a consequence of seizures per se.
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PMID:Electroconvulsive stimuli and brain peptides: effect of modification of seizure duration on neuropeptide Y, neurokinin A, substance P and neurotensin. 128 45

1. The effects of chemically induced convulsions, clinically similar to those elicited by electroconvulsive treatment (ECT), on brain regional distribution of neuropeptide Y-, neurokinin A-, substance P- and neurotensin-like immunoreactivities were studied in the rat. 2. Pentylenetetrazole (PTZ) and bicuculline (BIC) were used to induce grand mal seizures. Rats were divided into three groups receiving one of the following treatments: Saline, PTZ (45 mg/kg) or BIC (1.5 mg/kg). 3. After sacrifice by focused microwave irradiation, brains were dissected, peptides extracted and measured by specific radioimmunoassays. 4. Repeated grand mal convulsions induced by PTZ, in similarity to ECT, markedly increased NPY-LI concentrations in frontal cortex and hippocampus. In contrast to ECT, no changes in NKA- or SP-LI levels were seen. NT-LI was lowered in striatum. 5. Bicuculline effects were more circumscribed: some animals developed grand mal and died while convulsing (peptides not measured), others did not develop generalized seizures and were sacrificed after the fourth treatment. 6. The results demonstrate a similar effect of PTZ and ECT on regional NPY-LI concentrations and raise the possibility that grand mal, regardless of etiology, is necessary for effects on peptides.
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PMID:Brain neuropeptides: changes by treatment with the convulsants pentylenetetrazole and bicuculline. 149 30

The neuropeptides somatostatin, neurotensin and substance P were investigated in rats during and after limbic seizures induced by systemic injection of kainic acid (10 mg/kg, i.p.). Three hours after injection of the toxin, pronounced decreases (40-50%) in somatostatin-like immunoreactivity in frontal cortex, striatum, dorsal hippocampus and amygdala/pyriform cortex were observed. Concomitantly, neurotensin-like and substance P-like immunoreactivities were also reduced in the frontal cortex and the hippocampus. These early decreases in peptide levels may result from increased release and subsequent inactivation of the peptides during acute seizures. At later time intervals, 3, 10 and 30 days after injection of kainic acid, the initially decreased peptide levels were partially normalized. However, the reduction in somatostatin-like immunoreactivity in amygdala/pyriform cortex and striatum persisted up to 30 days. Neurotensin-like immunoreactivity remained decreased in the frontal cortex. On the other hand, neurotensin- and substance P-like immunoreactivities were increased in the striatum and substantia nigra 10-30 days after injection of kainic acid. These late changes in peptide levels may suggest destruction of peptidergic neurons or adaptive changes induced by the convulsions. Pretreatment of rats with cysteamine (100 mg/kg, i.p.), an agent which decreases brain somatostatin levels, had no effect on the intensity of kainic acid induced convulsions, although a slightly earlier onset of seizures was observed. The changes in peptide levels, especially the marked decreases in somatostatin content after systemic injection of kainic acid, suggest considerable acute and chronic alterations in peptidergic systems caused by limbic convulsions.
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PMID:Kainic acid induced seizures: changes in somatostatin, substance P and neurotensin. 242 20

There is now considerable evidence that putative neuropeptides are involved in epileptogenic processes. Neurotensin (NT), which affects neuronal excitability in many parts of the CNS, is potentially relevant to the kindling phenomenon, but has not previously been studied in the kindling model of epilepsy. This study compared the short term (24 hr) and long term (3 wk) effects of amygdaloid kindled seizures, and the short term effects of non-kindled seizures (cortical suprathreshold stimulation-induced seizures, STS), on the concentrations of NT in 13 brain regions in the rat. Whereas kindled seizures produced neither short term nor long term changes in NT, the STS resulted in altered NT concentrations, with a decrease in the cortex and increases in the hippocampus and cervical spinal cord. These results reveal seizure-type specific changes in NT in 3 brain regions; and indicate that although NT does not appear to be involved in kindling, it may be important in the neurochemical mechanisms underlying STS.
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PMID:Regional brain concentrations of neurotensin following amygdaloid kindled and cortical suprathreshold stimulation-induced seizures in the rat. 336 40

Ethanol (2.0-5.0 g/kg, IP) caused a dose-related impairment of the aerial righting reflex of mice 60 min after injection. Ethanol (3.5 g/kg, IP) given simultaneously with neurotensin (30 micrograms, IC), bombesin (30 micrograms, IC) or beta-endorphin (20 micrograms, IC) caused a greater impairment of the reflex than ethanol alone. Simultaneous treatment with ethanol (4.0 g/kg, IP) and thyrotropin-releasing hormone (TRH, 3.0-30 micrograms, IC) caused less impairment of this measure than ethanol alone. None of the peptides altered the height of aerial righting when administered alone, or when administered with ethanol no peptide altered blood or brain ethanol content. Unexpectedly, TRH (20 and 40 mg/kg, IP) potentiated the action of ethanol by increasing punished licking in water-deprived rats, rather than antagonizing this acute action of ethanol. Like ethanol (1.0 and 2.0 g/kg, IP), beta-endorphin (100 micrograms, IC) suppressed ethanol-withdrawal tremor and audiogenic-seizure susceptibility in ethanol-dependent rats. beta-Endorphin (1 microgram) and bombesin (10 and 30 micrograms, IC) reduced only audiogenic-seizure susceptibility. TRH (10-100 micrograms, IC, or 1-40 mg/kg, IV) and neurotensin (10-100 micrograms, IC) had no effect on these ethanol-withdrawal signs. These findings suggest that centrally active peptides may play a role in certain acute and chronic actions of ethanol. Because TRH, neurotensin, bombesin and beta-endorphin do not alter all actions of ethanol in the same way, an interaction of ethanol with many functionally independent neuronal circuits is suggested.
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PMID:Modification of the actions of ethanol by centrally active peptides. 626 62

Experiments were performed on male Wistar rats with the aim to study effects exerted by microinjections of somatostatin and neurotensin into lateral ventricle, amygdala, hippocampus and substantia nigra pars reticulata in case of epileptic activity. It was established that the mentioned neuropeptides exerted antiepileptic effect during seizures induced by corazol and picrotoxin, which was expressed by substantial elongation of the seizure latency and a decreasing of seizure intensity. It was shown that antiseizure activity of somatostatin and neurotensin was higher under conditions of picrotoxin-induced epileptic activity, than under conditions of that induced by corazol. A conclusion is made that somatostatin and neurotensin take part in epileptic activity regulation.
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PMID:[Effect of intracerebral injections of somatostatin and neurotensin on motor functions in seizure]. 791 97

We measured lumbar cerebrospinal fluid (CSF) levels of somatostatin, cholecystokinin, neurotensin, atrial natriuretic factor, vasoactive inhibitory peptide, neuropeptide Y, adrenocorticotrophic hormone, corticotropin releasing hormone, beta-endorphin, metenkephalin, cortisol, alanine, glycine, aspartate, glutamate, taurine, and gamma-aminobutyric acid in 25 inpatients with epilepsy at known interictal and postictal times and in 11 neurologically normal volunteers. There were no significant differences between interictal or postictal complex partial seizures (CPS), postictal generalized tonic-clonic seizures (GTC), and control CSF neuropeptide, cortisol, and amino acid (AA) levels. However, there were nonsignificant trends for CSF levels of several neuropeptides to be increased after CPS and GTC as compared with interictal baseline levels. There were significant correlations between levels of certain CSF neuropeptides or (AAs) and serum antiepileptic drug (AED) levels. Several correlations were noted between CSF levels of AAs, including a correlation between the excitatory neurotransmitters aspartate and glutamate identified only after CPS.
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PMID:Cerebrospinal fluid levels of neuropeptides, cortisol, and amino acids in patients with epilepsy. 809 91

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

Neurotensin (NT) is an endogenous neuropeptide involved in a variety of central and peripheral neuromodulatory effects. Herein we show the effects of site-specific glycosylation on the in vitro and in vivo pharmacological properties of this neuropeptide. NT analogues containing O-linked disaccharides (beta-melibiose and alpha-TF antigen) or beta-lactose units linked by a PEG(3) spacer were designed and chemically synthesized using Fmoc chemistry. For the latter analogue, Fmoc-Glu-(beta-Lac-PEG(3)-amide) was prepared. Our results indicate that the addition of the disaccharides does not negatively affect the sub-nanomolar affinity or the low-nanomolar agonist potency for the neurotensin receptor subtype 1 (NTS1). Interestingly, three glycosylated analogues exhibited sub-picomolar potency in the 6 Hz limbic seizure mouse model of pharmacoresistant epilepsy following intracerebroventricular administration. Our results suggest for the first time that chemically modified NT analogues may lead to novel antiepileptic therapies.
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PMID:Glycosylated neurotensin analogues exhibit sub-picomolar anticonvulsant potency in a pharmacoresistant model of epilepsy. 1917 15

NAP (NAPVSIPQ, generic name, davunetide), a neuroprotective peptide in clinical development for neuroprotection against Alzheimer's disease and other neurodegenerative indications, has been recently shown to provide protection against kainic acid excitotoxicity in hippocampal neuronal cultures. In vivo, kainic acid toxicity models status epilepticus that is associated with hippocampal cell death. Kainic acid toxicity has been previously suggested to involve the microtubule cytoskeleton and NAP is a microtubule-interacting drug candidate. In the current study, kainic acid-treated rats showed epileptic seizures and neuronal death. Injection of NAP into the dentate gyrus partially protected against kainic acid-induced CA3 neuron death. Microarray analysis (composed of > 31 000 probe sets, analyzing over 30 000 transcripts and variants from over 25 000 well-substantiated rat genes) in the kainic acid-injured rat brain revealed multiple changes in gene expression, which were prevented, in part, by NAP treatment. Selected transcripts were further verified by reverse transcription coupled with quantitative real-time polymerase chain reaction. Importantly, among the transcripts regulated by NAP were key genes associated with proconvulsant properties and with long-lasting changes that underlie the epileptic state, including activin A receptor (associated with apoptosis), neurotensin (associated with proper neurotransmission) and the Wolfram syndrome 1 homolog (human, associated with neurodegeneration). These data suggest that NAP may provide neuroprotection in one of the most serious neurological conditions, epilepsy.
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PMID:The microtubule interacting drug candidate NAP protects against kainic acid toxicity in a rat model of epilepsy. 1979 11


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