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)

The enzymes of the cholinergic system have been investigated in discrete brain areas in alcohol-dependent rats, which were still intoxicated or were undergoing withdrawal. The ethanol intoxication resulted in a slight, but significant increase in choline acetyltransferase (CAT) activity in the caudate nucleus both 1 and 7 h after the last dose of ethanol. We also found a significant decrease in CAT activity in the temporal limbic cortex while rats were highly intoxicated. All other brain regions investigated, e.g., cerebellum, pons-medulla, frontoparietal cortex, hypothalamus and septum showed unchanged CAT activity. Rats were also analysed immediately following the onset of a withdrawal-induced audiogenic convulsive seizure where, in addition to the striatum, depressed CAT activity was observed in the hippocampus. In all the analysed situations acetylcholinesterase activity remained unchanged. These results show that ethanol intoxication leads to a perturbation in the synthetic capacity of acetylcholine in certain defined brain structures and that this may have some correlation to the observed behavioural impairments.
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PMID:Cholinergic involvement in ethanol intoxication and withdrawal-induced seizure susceptibility. 10 88

The effects of unilateral injection of kainic acid into the rate hippocampus have been examined in terms of morphologic, neurochemical and behavioral sequelae. Infusion of 10 nmoles if kainate causes a rapid and complete degeneration of neuronal perikarya in the entire hippocampal formation followed by gliosis and atrophy of the region. This unilateral neuronal loss is accompanied by a 50% decrease in the specific activity of the biochemical markers for GABAergic neurons including glutamic acid decarboxylase, endogenous GABA and synaptosomal uptake of [3H]GABA. The extrinsic hippocampal cholinergic and noradrenergic afferents also exhibit significant alteration. Although the specific activity of choline acetyltransferase is unaffected and the specific activity of tyrosine hydroxylase is significantly increased in the injected hippocampus, the synaptosomal high affinity uptake process for [3H]choline and [3H]norepinephrine are significantly reduced at 10 days after injection. Whereas the level of endogenous acetylcholine is elevated in the lesioned hippocampus at 2 days after injection, the level of endogenous norepinephrine is reduced. For several hours after intrahippocampal injections of 5 nmoles or more of kainate, rats exhibit epileptiform behavior. Intrahippocampal injection of kainate may be a useful rodent model for temporal lobe seizure disorders.
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PMID:Microinjection of kainic acid into the rat hippocampus. 68 77

Because previous work showed that in the newborn brain, but not in the adult brain, glutamate decarboxylase (GAD) is notably susceptible to heat, we have studied the possible involvement of GAD inhibition in febrile convulsions and the related changes in gamma-aminobutyric acid (GABA) content. Rats of different ages were subjected to hyperthermia, and GAD activity was determined in brain homogenates by measuring the release of 14CO2 from labeled glutamate and by measuring the formation of GABA. The latter method gave considerably lower values than the former in the youngest rats, and was considered more reliable. With this method, we found a 37-48% inhibition of GAD activity in rat pups 2-5 days old, which showed febrile seizures at progressively higher body temperatures, whereas in 10- and 15-day-old animals, which did not show convulsions, GAD activity was not affected by hyperthermia. Whole-brain GABA levels, however, did not change at any age. In contrast to GAD, choline acetyltransferase and lactic dehydrogenase activities were not altered by hyperthermia at any of the ages studied. These results suggest that a decreased efficiency of the inhibitory neurotransmission mediated by GABA, consequent to the inhibition of GAD activity, may be a factor related to febrile convulsions.
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PMID:Inhibition of brain glutamate decarboxylase activity is related to febrile seizures in rat pups. 172 43

Three days after systemic administration of kainic acid (15 mg/kg, s.c.), selected cholinergic markers (choline acetyltransferase, acetylcholinesterase, muscarinic acetylcholine receptor, and high-affinity choline uptake) and GABAergic parameters [benzodiazepine and gamma-aminobutyric acid (GABA) receptors] were studied in the frontal and piriform cortex, dorsal hippocampus, amygdaloid complex, and nucleus basalis. Kainic acid treatment resulted in a significant reduction of choline acetyltransferase activity in the piriform cortex (by 20%), amygdala (by 19%), and nucleus basalis (by 31%) in comparison with vehicle-injected control rats. A lower activity of acetylcholinesterase was also determined in the piriform cortex following parenteral kainic acid administration. [3H]Quinuclidinyl benzilate binding to muscarinic acetylcholine receptors was significantly decreased in the piriform cortex (by 33%), amygdala (by 39%), and nucleus basalis (by 33%) in the group treated with kainic acid, whereas such binding in the hippocampus and frontal cortex was not affected by kainic acid. Sodium-dependent high-affinity choline uptake into cholinergic nerve terminals was decreased in the piriform cortex (by 25%) and amygdala (by 24%) after kainic acid treatment. In contrast, [3H]flunitrazepam binding to benzodiazepine receptors and [3H]muscimol binding to GABA receptors were not affected 3 days after parenteral kainic acid application in any of the brain regions studied. The data indicate that kainic acid-induced limbic seizures result in a loss of cholinergic cells in the nucleus basalis that is paralleled by degeneration of cholinergic fibers and cholinoceptive structures in the piriform cortex and amygdala, a finding emphasizing the important role of cholinergic mechanisms in generating and/or maintaining seizure activity.
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PMID:Changes in cholinergic but not in GABAergic markers in amygdala, piriform cortex, and nucleus basalis of the rat brain following systemic administration of kainic acid. 254 59

We studied the effect of pentylenetetrazol (PTZ)-induced kindling (35 mg/kg, i.p., daily) on somatostatin-like immunoreactivity (SOM) with special attention to the duration of changes (rats were sacrificed either 10 days or 4 months after the development of kindling) and to transmitters or modulators related to somatostatin (neuropeptide Y (NPY), GABA, choline acetyltransferase (ChAT), acetylcholinesterase (AchE]. In rats sacrificed 10 days after the last kindled seizure, SOM was elevated in frontal cortex and striatum (p less than 0.01); NPY was elevated in frontal cortex, striatum and hippocampus (p less than 0.05) of kindled or prekindled rats (i.e., rats which were treated daily with PTZ but did not express three consecutive generalized seizures). ChAT activity was slightly decreased (p less than 0.05) in cortex. GABA levels and AchE activity were unchanged in kindled cortex. In rats sacrificed 4 months after the development of kindling none of the parameters analyzed differed from controls. The present study suggests that the cortical and striatal neurons containing SOM/NPY are affected by PTZ-kindling. The cortical cholinergic system is affected to a much smaller extent. The neuropeptide changes are not persistent, as is the lowered seizure threshold, so they are probably not involved in the maintainance of the latter.
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PMID:Somatostatin, neuropeptide Y, GABA and cholinergic enzymes in brain of pentylenetetrazol-kindled rats. 257 17

With a combination of electrolytic lesion and choline acetyltransferase histochemistry, Kimura et al. suggested that cholinergic neurons in the substantia innominata (SI) plays an important role in accessing non-motor structure, such as the amygdala (AM), to the motor system during AM kindling. More recent studies demonstrated that intra-SI injection of GABAergic agent or excitatory amino acid antagonist suppresses the kindled generalized convulsion without blocking afterdischarge (AD) generation in the AM. In order to gain further insight into the role played by the SI in AM kindling, we examined the comparative electroclinical features of AM and SI kindling in addition to the transferability of the SI to the ipsilateral AM. Male Wistar rats were electrically kindled at the left AM or the left SI at the AD threshold (ADT) until five consecutive Stage 5 generalized convulsions were evoked. Subsequently, the stimulus intensity was gradually reduced and the last intensity to induce Stage 5 seizure was designated as the generalized seizure triggering threshold (GST). Following the determination of the GST, the SI stimulation was switched to the ipsilateral AM. All the animals were perfused and electrode placements were identified histologically. The electrode placements distributed in the medial SI (N = 5), lateral SI (N = 9), Globus Pallidum (GP) (N = 5) and Nucleus Accumbens (NA) (N = 2). All electrodes of the AM (N = 9) were located within the AM. The 3/5 of GP rats kindled, while the 2/5 did not kindle. The 2/2 of NA rats kindled.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Substantia innominata kindling in rats]. 271 64

Nonsynaptic mitochondria isolated from rat brain hippocampus were compared with those obtained by means of the same preparative procedure from cerebral cortex and striatum. Protein recovery, marker enzyme activities (lactate dehydrogenase, citrate synthase, and acid phosphatase), state 4 respiration, and response to hypoosmotic shock showed no difference among the three cerebral regions, suggesting homogeneous behavior during the subfractionation procedure. Cholinergic markers--choline acetyltransferase, acetylcholinesterase activities, and high-affinity choline uptake--evaluated on synaptosomes showed the classic regional pattern with an enrichment in the striatum (striatum much greater than hippocampus). The coupling state of the mitochondrial fractions was maintained (respiratory control ratios ranging from 3.62 to 5.08 with glutamate + malate as oxidizable substrates), showing a metabolic competence sufficient to perform metabolic studies. Regional differences were found in state 3, uncoupled state of respiration, and cytochrome oxidase activity. Hippocampus showed the lower values (hippocampus less than striatum less than cortex). A possible role of this lower capacity of mitochondrial energy metabolism in determining the sensitivity of hippocampal neurons to ischemia or epileptic seizures is suggested.
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PMID:Oxidative metabolism of nonsynaptic mitochondria isolated from rat brain hippocampus: a comparative regional study. 283 1

We have tested several compounds interfering with the brain monoamine (noradrenaline, dopamine, serotonin) and acetylcholine systems for their effects on limbic seizures produced by systemically (s.c.) injected kainic acid as well as on neurochemical changes in amygdala/pyriform cortex resulting from the kainic acid treatment. The characteristic neurochemical changes induced by s.c. kainic acid were a decrease in noradrenaline and an increase in 5-hydroxyindoleacetic acid in the acute (3 h after kainic acid injection) suggesting strongly increased neurotransmitter turnover in noradrenergic and serotonergic neurons. This was followed by a reduction of glutamic acid decarboxylase and choline acetyltransferase activities during the chronic phase (3 days) of the kainic acid action, indicating destruction of GABAergic and cholinergic neurons. The compounds tested in this model of limbic epilepsy included 1-propranolol, prazosin, clonidine, yohimbine, metergoline, atropine and haloperidol. Among these compounds the alpha 2-adrenergic agonist clonidine (0.1 mg/kg, i.p.) exhibited a powerful protective action on kainic acid-induced limbic seizures as well as on the neurochemical changes in the amygdala and pyriform cortex. In addition, the adrenoceptor antagonists prazosin (alpha 1) and propranolol (beta) as well as the dopamine receptor antagonist haloperidol had significant but less potent - protective actions upon kainic acid-induced seizures and subsequent neurochemical changes. On the other hand, yohimbine (alpha 2-antagonist) and metergoline (serotonin-antagonist) potentiated the limbic seizure syndrome and no effect was found with atropine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alpha 2-adrenoceptors modulate kainic acid-induced limbic seizures. 299 67

Seizure-experienced Genetically Epilepsy-prone Rats (GEPRs) have increased acetylcholine content and choline acetyltransferase activity in the thalamus and striatum. These cholinergic differences are accompanied by a slight but statistically significant reduction in acetylcholinesterase activity in the midbrain. In addition, no abnormalities were found in the numbers of specific 3H-QNB binding sites in the striatum, hippocampus, inferior colliculi or cortex. Other work has shown no difference in muscarinic receptor function as measured by carbachol-stimulated inositol-1-phosphate formation. These data suggest a possible presynaptic defect in the striatal and thalamic cholinergic system which may play some role in the seizure-prone state of the GEPR. However, caution must be used in interpreting these cholinergic derangements since more recent findings show no differences in thalamic acetylcholine content in seizure-naive GEPRs. Thus, the original cholinergic abnormalities detected in the seizure-experienced GEPR may be an enduring response to seizure activity.
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PMID:Abnormalities in the central cholinergic transmitter system of the genetically epilepsy-prone rat. 301 14

The effect of mannitol treatment on the behavioural, morphological and neurochemical brain damage induced after subcutaneously applied kainic acid (10 mg/kg) was studied in the rat. Mannitol at a dose of 1.5 g/kg was injected intravenously 10 min, 1.5 h and 3 h respectively after kainic acid administration. A protective effect of mannitol was observed only when mannitol was given 1.5 h after kainic acid application, i.e. within the early phase of kainic acid-induced brain oedema development. At this time period, mannitol prevented the development of kainic acid-induced seizures as well as irreversible brain lesions and neurochemical changes, the latter being reduction of noradrenaline levels in amygdala/pyriform cortex measured 3 h, and reduction of glutamate decarboxylase and choline acetyltransferase activities measured 3 days after kainic acid treatment. Similarly loss of glutamate decarboxylase activity in dorsal hippocampus induced by kainic acid was prevented by mannitol treatment. It is concluded that by washing out brain oedema, mannitol treatment may prevent propagation of seizures and brain damage in the kainic acid model of epilepsy.
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PMID:Effect of mannitol treatment on brain neurotransmitter markers in kainic acid-induced epilepsy. 311 66


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