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)

Early Pb exposure is known to disrupt the development of the hippocampus and result in deficits in learning and memory capacities and altered seizure susceptibility. The excitatory amino acid, NMDA, is found in high concentrations in the hippocampus and has been implicated in learning and memory functions and seizure activity. Rat pups nursed mothers exposed to high (4%), moderate (0.4%), or low (0.05%) levels of PbCO3 in their diet, or a Na2CO3 control diet from postnatal day 1 (P1) to P25. Rat pups were injected with varying doses of NMDA on P15 or P25. Control animals showed a characteristic slowly developing response to NMDA, usually including tail twitches and wet dog shakes at approximately 10 and 40 mg/kg at P15 and P25, respectively, with status epilepticus and death occurring at 40 and 80 mg/kg. Lead-exposed animals displayed an altered sensitivity to NMDA, with high and medium Pb animals showing the onset of behavioral signs and death at lower NMDA doses, the degree of which being dependent on the level of Pb exposure. Low Pb-exposed animals showed a more variable and attenuated response to NMDA. The data are discussed in terms of the possible mechanisms of Pb neurotoxicity.
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PMID:Altered sensitivity to NMDA following developmental lead exposure in rats. 140 40

To assess long-term metabolic consequences of recurrent ictal events arising during development, seizures were repeatedly generated in rats at different stages of cerebral maturation. Seizures were induced by i.p. injections of bicuculline for three consecutive days, starting from postnatal day 5 (P5), when the brain is very immature, or from P15, a period at which the brain is more structurally organized. Local cerebral metabolic rates for glucose were measured in 74 structures at P15, P25 and in adults (P60), by the autoradiographic method using 2-D-[14C]deoxyglucose. Repeated seizures in P5 to P7 pups led to a reduction (16-34%) of glucose consumption at P15, mainly significant in sensory, motor and functionally non-specific areas as well as in cerebellar nuclei. Selective decreases in metabolic activity were still recorded in adults, mostly in auditory system (20%) and cerebellar nuclei (27%). Seizures generated from P15 to P17 led to an overall mortality rate of 62% (versus 22% at P5 to P7). Surviving animals exhibited reduced metabolic rates for glucose (by 7-27%) at P25, significant in 23 structures, and depicting pronounced changes in limbic, hypothalamic, sensory and white matter areas, whereas brain functional activity finally returned to basal values at P60. Therefore, while younger rats seemed to better tolerate repeated bicuculline-induced seizures than older animals, the reverse was true for long-term metabolic effects, and the more immature the brain when seizures arise, the more persistent the functional consequences.
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PMID:Medium- and long-term effects of repeated bicuculline-induced seizures in developing rats on local cerebral energy metabolism. 968 3

Previous studies have shown an association among seizures, neuronal death and the expression of cellular immediate-early genes (cIEG). To understand further the relationship between these processes, we investigated the ability of kainic acid (KAI) to induce behavioral responses and gene expression in the hippocampus of developing fos-lacZ transgenic mice. Despite the fact that KAI elicited seizure-like activity from P2 onwards, Fos-lacZ was first detected at P5 in CA3 pyramidal neurons. Thus, intense behavioral responses were not invariably associated with fos-lacZ expression. Furthermore, while adult CA3 neurons are highly susceptible to KAI toxicity, they are resistant at P5. Therefore, the presence of Fos-lacZ in CA3 neurons is not necessarily predictive of their fate. By P10, Fos-lacZ was induced in CA3 neurons and in the most mature granule neurons of the dentate gyrus (DG). Between P15 and P20, KAI induced fos-lacZ in all CA1 and CA3 pyramidal neurons and most granule neurons of the DG. This stereotypical pattern of fos-lacZ expression mirrors the ontogeny of hippocampal circuitry and glutamate signalling. Thus the fos-lacZ mice can be used to map the functional maturation of the nervous system with single cell resolution. The scope of this approach was extended by administration of additional chemoconvulsants to fos-lacZ mice and by analysis of fos-lacZ transgenic mice with mutations in their FAP site. These additional studies revealed anatomical and mechanistic differences in glutamate receptor-mediated transcriptional responses in the nervous system.
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PMID:A gene expression approach to mapping the functional maturation of the hippocampus. 983 29

Activated mitogen-activated protein (MAP) kinases play an essential role controlling many neuronal functions. Dual specificity protein phosphatases (DS-PTPs) elicit selective inactivation of MAP kinases and are under tight transcriptional control. We have studied expression of four DS-PTPs (MKP-1, MKP-X, MKP-3 and B23) in rat brain and examined changes during post-natal development and following kainic acid induced seizure activity. In normal adult brain these DS-PTPs exhibit a strikingly different expression pattern. Only MKP-1 was regulated during development with levels increased transiently (P15-P21) within the thalamus and somatosensory cortex. Following kainate treatment, MKP-1, MKP-3 and B23 all exhibit striking changes in expression within hippocampal subfields CA1-3 and dentate gyrus. Regulated transcription of DS-PTPs may play a critical role controlling MAP kinase dependent processes including synaptic remodeling and neuronal death.
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PMID:Regulated expression of dual specificity protein phosphatases in rat brain. 992 51

To investigate if AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor activation contributes to acute manifestations and long term consequences of status epilepticus (SE), we administered the AMPA receptor antagonist NBQX to P35 rats undergoing kainic acid (KA)-induced SE. NBQX (30 mg/kg/dose) given intraperitoneally (i.p.) at 30, 60 and 90 min after i.p. KA injection (12 mg/kg) reduced severity of SE. When tested as adults, rats that had received KA and NBQX were similar to controls with no long term impairment in visuospatial memory (assessed by the water maze test), or histologic damage in the CA1 or CA3 hippocampal subfields. However, both P35 groups, those receiving KA alone and those receiving KA and NBQX, had similar rates of spontaneous recurrent seizures (SRS). In P15 rats, NBQX resulted in increased acute mortality from KA associated SE. These results indicate that the effects of NBQX on KA-induced SE are age dependent, and that non-NMDA receptor activation contributes to the acute manifestations and to the long term sequelae seen after KA-induced SE in the prepubescent rat brain.
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PMID:Consequences of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor blockade during status epilepticus in the developing brain. 1006 83

In order to assess long-lasting consequences of recurrent seizures during development, the effects of repeated seizures in developing rats were investigated on brain adenosine A1 and A2A receptors. The characteristics of A1 and A2A receptors were analyzed by measuring the binding of the selective agonists [3H]CHA (N6-cyclohexyladenosine) and [3H]CGS 21680 (2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamido adenosine), respectively, on cerebral membrane preparations, whereas receptor coupling to G-proteins was examined by using a GTP analogue (Gpp(NH)p; guanylyl-5'-imidodiphosphate). Seizures were induced by bicuculline once a day at two different developmental stages: either from postnatal day 5 to postnatal day 7 (P5-P7) or from P15 to P17. Adenosine receptors were then studied at P15, P25 and P60. P5-P7 seizures led to an increase in A1 receptor density at P60 and to a decrease in their coupling to G-proteins at P15, but they did not affect A2A receptors. P15-P17 seizures decreased the coupling of A1 receptors to G-proteins at P25 and P60, reduced the density of A2A receptors at P25 and increased their affinity at P60. These results depict a persistent sensitivity of both A1 and A2A brain adenosine receptors to repeated seizures, with selective receptor alterations according to the cerebral maturational stage when seizures occur. In respect to the neuromodulatory and anticonvulsant properties of adenosine, such changes might be implicated in long-term functional brain reorganization after early seizures and future susceptibility to convulsive disorders.
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PMID:Medium- and long-term alterations of brain A1 and A2A adenosine receptor characteristics following repeated seizures in developing rats. 1041 17

Glutamate NMDA receptor has been implicated in brain developmental processes as well as in excitotoxicity and seizure mediation. A previous study has shown that an acute episode of seizures for 30 min in rats altered NMDA receptor characteristics, mainly in the very immature animal. In order to assess whether receptor modifications may also account for long-lasting cerebral disabilities, medium- and long-term consequences of repeated seizures in developing rats on brain NMDA receptor properties were investigated. Seizures were induced once a day for 3 consecutive days, either from post-natal day 5 (P5) to P7 or from P15 to P17. NMDA receptors were then analysed at P15, P25 and P60 (adulthood) by measuring specific binding of [3H]MK-801 on brain membrane preparations. In addition, allosteric modulation of NMDA receptors by exogenous glutamate and glycine was investigated. Seizures from P5 to P7 led to a 22% increase in the density of [3H]MK-801 binding sites measured at P15, but did not affect NMDA receptor density or affinity at P25 or P60. P15-P17 seizures led to a 21% decrease in the density of binding sites and to a 33% decrease in receptor dissociation constant at P25, while they were without effect at P60. Moreover, P5-P7 and P15-P17 seizures were both associated with a suppression of the glutamate/glycine-induced receptor activation at P60. These modifications might account for long-term alterations in cerebral excitability or plasticity after early convulsive disorders, with regards to altered cognitive capacities, epileptogenesis and brain susceptibility to recurrent seizures.
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PMID:Repeated seizure-associated long-lasting changes of N-methyl-D-aspartate receptor properties in the developing rat brain. 1047 71

Neuronal activity is a requirement for the plasticity and normal development of the central nervous system. We have used differential cloning techniques to identify an immediate-early gene (IEG) that is rapidly induced in neurons by activity in both adult and developmental models of plasticity. Here we describe the key regulatory enzyme of polyamine catabolism, spermidine/spermine N1-acetyltransferase (SSAT), as a neuronal IEG. In the rat brain, kainate-induced seizures result in a 5.5-fold increase in the amount of SSAT mRNA above basal levels and the enzymatic activity is increased twofold. Expression of SSAT mRNA is rapidly and transiently upregulated in the cerebral cortex and hippocampus by seizure-induced neuronal activation. In hippocampal neurons, SSAT expression is dynamically responsive to synaptic activity in the long-term potentiation (LTP) paradigm. In developing brain, region-specific expression of SSAT mRNA is first detected at postnatal day 9 (P9) and subsequently increases through days P15, P20, before reaching maximal level in adult animals. This dynamic transcriptional and translational control suggests that SSAT may play a role in activity-dependent neuronal plasticity and development.
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PMID:Regulation of SSAT expression by synaptic activity. 1129 8

OBJECTIVE: To verify the effects of malnutrition and nutritional rehabilitation regarding seizure threshold, body weight and brain weight in rats. METHODS: Pregnant Wistar rats and their pups were used. Part of the rat pups were submitted to a malnutrition protocol and the rest served as nourished controls. At P15, malnourished and control rats were submitted to status epilepticus induced by flurothyl; and the rehabilitation period started after recovery from seizures. At P30, all rats were submitted to single flurothyl-induced seizures and the threshold was determined. After the seizures, the rats were sacrificed, the brain removed and weighed. Rat pups were weighed daily from age P2 to P30. RESULTS: Significant differences as to body weight between malnourished and nourished rats were observed from P5 onwards. At P30, even after nutritional rehabilitation, there were still differences in terms of body weight. Nourished (mean 1.47 g -/+ 0.17) and male (mean 1.47 g -/+ 0.16) rats had brain weight slightly higher than that presented by malnourished (mean 1.42 g -/+ 0.17) and female (mean 1.38 g -/+ 0.12) rats; however, the difference was not significant. Differences observed in the threshold for the first clonic and tonic seizure at ages P15 and P30 between the groups were not statistically significant. CONCLUSIONS: Our results suggest that malnutrition does not influence seizure threshold in rat pups submitted to flurothyl-induced seizures. Early nutritional rehabilitation seems to have a protective effect on seizure threshold in previously malnourished animals.
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PMID:[Effects of early malnutrition and nutritional rehabilitation in rats] 1464 10

Unlike adults, kainic acid (KA)-induced status epilepticus (SE) in immature rats causes neither cell death nor recurrent spontaneous seizures. To elucidate the mechanisms of these distinct responses, transcriptional changes in neuropeptides were examined following KA-induced SE. We aimed to determine whether neuropeptides with anticonvulsant/neuroprotective properties were preferentially increased in immature rats while those with a proconvulsant/neurotoxic role were elevated to a greater extent in mature rats. We used high-density oligonucleotide gene arrays and directly compared transcriptional regulation of seven select neuropeptides at P15 and P30 over five time points. Total RNAs were isolated from hippocampi of 12 animals and pooled to hybridize to triplicate Affymetrix Genechips. Microarray results were validated by real-time quantitative RT-PCR (qRT-PCR). Independent individual RNA samples were purified for triplicate runs of qRT-PCR. Neuropeptides are significantly regulated by seizures in both immature and mature hippocampus. The magnitude of increase is significantly higher at P30 compared with that at P15, not only for neuropeptides with neurotoxic/proconvulsant properties but also for those with neuroprotective/ anticonvulsant properties. Galanin is induced at 24 h only in P30 rats. CST shows high expression in immature hippocampus and is further increased after KA-induced SE only in P15. The expression trends seen in the microarray data are confirmed by qRT-PCR for all six neuropeptides analyzed. CST might play a neuroprotective role in immature rats, and its overexpression might prevent neuronal loss after seizure in adults. Also, suppression of tachykinin and corticotropin-releasing hormone might be effective in alleviating seizure-induced neuronal damage.
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PMID:Microarray analysis of postictal transcriptional regulation of neuropeptides. 1580 Mar 81


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