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)

Previous studies demonstrated that the spiny rat Proechimys guyannensis exhibits resistance to experimental epilepsy. Neural activation was studied in the Proechimys hippocampus, using Fos induction, within 24 h after pilocarpine-induced seizures; neurodegenerative events were investigated in parallel, using FluoroJade B histochemistry. These parameters were selected since pilocarpine-induced limbic epilepsy is known to elicit immediate early gene expression and cell loss in the hippocampus of seizure-prone laboratory rodents. At variance with matched experiments in Wistar rats, pilocarpine injection resulted in Proechimys in seizure episodes that, as previously reported, did not develop into status epilepticus. At 3 h and 8 h after seizure onset, Fos immunoreactivity filled the dentate gyrus of both rat species, and was quite marked in pyramidal cells of the Proechimys Ammon's horn. At 24 h, Fos immunoreactivity dropped in the Wistar hippocampus and persisted in Proechimys. At 8 h and 24 h, FluoroJade-stained neurons were very few in the Proechimys hippocampus, whereas they were abundant in that of Wistar rats. Double immunohistochemistry for Fos and parvalbumin, the protein expressed by fast-spiking hippocampal interneurons, indicated that Fos was induced up to 24 h in the vast majority of parvalbumin-containing cells of the Proechimys hippocampus, and in a minority of these cells in the Wistar hippocampus. The findings demonstrate that early postepileptic neurodegeneration is very limited in the Proechimys hippocampus, in which sustained Fos induction persists for several hours. The findings also indicate that Fos induction and persistence may not correlate with seizure intensity and may not be associated with neuronal death. Finally, the data implicate differential mechanisms of interneuron activity in anti-convulsant and pro-convulsant phenomena.
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PMID:Fos induction and persistence, neurodegeneration, and interneuron activation in the hippocampus of epilepsy-resistant versus epilepsy-prone rats after pilocarpine-induced seizures. 1538 58

Low-dose radiosurgery is presently in use as a treatment modality for focal epilepsy, but the mechanisms underlying the associated changes in seizure expression are poorly understood. We investigated whether total and parvalbumin expressing (PV+) neuronal densities within the hippocampus and amygdala are affected by analogous focal irradiation in amygdala-kindled rats. Adult rats were kindled by electrical stimulation through 10 stage 5 seizures. The kindled amygdala was then focally irradiated at 18 or 25 Gy, and generalized seizure thresholds were subsequently monitored for approximately 6 months. Histological and immunohistochemical assays of total and PV+ neuronal densities were performed bilaterally throughout the hippocampus and within the basolateral amygdala. PV+ neuronal densities were unaffected by kindling or irradiation in these regions. Kindling selectively reduced neuronal densities in the dentate granule cell layer, and medial CA3 pyramidal cell layer. Irradiation at 25 Gy, but not at 18 Gy, prevented or reversed this kindling-associated reduction in density.
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PMID:Effects of kindling and irradiation on neuronal density in the rat dentate gyrus. 1550 Sep 64

Parvalbumin (Pv) containing fast spiking neurons play a crucial role in synchronizing the activity of excitatory neuronal circuits in the brain. Alterations of parvalbumin content in these neurons can affect their spike characteristics and, ultimately, may increase the susceptibility of neuronal circuits to epileptic seizures. In the present study, we examined whether repeated 4-aminopyridine (4-AP)-induced seizures modify the regional parvalbumin contents in the rat brain. 4-Aminopyridine was injected intraperitoneally in adult rats, controls received the solvent. Animals were sacrificed at 3 h after a single acute treatment, or following repeated, daily treatments of 12 days. In situ hybridization (ISH) indicated significantly decreased parvalbumin mRNA level in the medial mammillary nucleus (MM) at 12 days. Western blotting revealed 20.1% significant decrease of parvalbumin content in the medial mammillary area, while parvalbumin immunohistochemistry indicated no change of the number of immunoreactive cells in the medial mammillary nucleus. The results reveal the downregulation of the transcription of the parvalbumin gene and the decrease of parvalbumin synthesis in medial mammillary nucleus neurons in response to experimental seizures.
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PMID:Repeated 4-aminopyridine seizures reduce parvalbumin content in the medial mammillary nucleus of the rat brain. 1553 Jun 59

Temporal lobe epilepsy (TLE) is known to be linked to an impaired balance of excitation and inhibition. Whether inhibition is decreased or preserved in the human epileptic hippocampus, beside the excess excitation, is still a debated question. In the present study, quantitative light and electron microscopy has been performed to analyse the distribution, morphology and input-output connections of parvalbumin (PV)-immunopositive interneurons, together with the entire perisomatic input of pyramidal cells, in the human control and epileptic CA1 region. Based on the degree of cell loss, the patients with therapy-resistant TLE formed four pathological groups. In the non-sclerotic CA1 region of TLE patients, where large numbers of pyramidal cells are preserved, the number of PV-immunopositive cell bodies decreased, whereas axon terminal staining, and the distribution of their postsynaptic targets was not altered. The synaptic coverage of CA1 pyramidal cell axon initial segments (AISs) remained unchanged in the epileptic tissue. The somatic inhibitory input is also preserved; it has been decreased only in the cases with patchy pyramidal cell loss in the CA1 region (control, 0.637; epileptic with mild cell loss, 0.642; epileptic with patchy cell loss, 0.424 microm synaptic length/100 microm soma perimeter). The strongly sclerotic epileptic CA1 region, where pyramidal cells can hardly be seen, contains a very small number of PV-immunopositive elements. Our results suggest that perisomatic inhibitory input is preserved in the epileptic CA1 region as long as pyramidal cells are present. Basket and axo-axonic cells survive in epilepsy if their original targets are present, although many of them lose their PV content or PV immunoreactivity. An efficient perisomatic inhibition is likely to take part in the generation of abnormal synchrony in the non-sclerotic epileptic CA1 region, and thus participate in the maintenance of epileptic seizures driven, for example, by hyperactive afferent input.
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PMID:Surviving CA1 pyramidal cells receive intact perisomatic inhibitory input in the human epileptic hippocampus. 1617 16

Although reduced calcium binding protein (CBP) immunoreactivities in the epileptic hippocampus have been well established, it has been controversial that these changes may directly indicate neuronal degeneration. In the present study, therefore, we investigated CBP expressions in the gerbil hippocampus following treatment with gamma-aminobutyric acid (GABA) receptor antagonists in order to assess whether altered CBP expressions are the result of either abnormal excitation or indicative of neuronal damage/degeneration. Seizure-sensitive (SS) gerbils showed a loss/decline of CBP immunoreactivities in some hippocampal neurons as compared with seizure-resistant (SR) gerbils. In muscimol (GABA(A) receptor agonist) treated SS gerbils, expression levels of CBP were enhanced as compared with saline-treated SS gerbils. Bicuculline (a GABA(A) receptor antagonist) treatment markedly reduced CBP immunoreactivities in hippocampal neurons of the SR gerbil. Baclofen (a GABA(B) receptor agonist) treatment increased CBP immunoreactivities in the hippocampus of SS gerbils, although its effect was lower than that of muscimol treatment. Moreover, phaclofen (GABA(B) receptor antagonist) treated SR gerbil showed reduction in calbindin D-28K immunoreactivity, not parvalbumin immunoreactivity, in the hippocampus. These findings therefore suggest that reduced CBP immunoreactivities may be the consequence of abnormal discharge caused by loss of GABAergic inhibition rather than an indication of the neuronal damage/degeneration.
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PMID:Effects of GABAergic transmissions on the immunoreactivities of calcium binding proteins in the gerbil hippocampus. 1577 49

We have mapped the macaque amygdala for the distribution of synaptic zinc (Zn), a co-factor of glutamate implicated in plasticity, as well as in several excitotoxic and other pathophysiological conditions. In brief, we found that the amygdala is Zn enriched in all nuclear groups (i.e., basolateral and cortical groups, as well as central and medial nuclei) but with marked differences in density. By comparing parallel tissue series histologically reacted for Zn and parvalbumin (PV), we further found that regions high in Zn are typically low in PV neuropil. In the basolateral group, there is a particularly distinct dorsoventral gradation such that Zn levels are most dense ventrally, i.e., in the paralaminar nucleus, the ventral division of the lateral nucleus, and the parvicellular divisions of both the basal nucleus and the accessory basal nucleus. PV levels are least dense in these same regions. For the central and medial nuclei, there is a slight mediolateral gradient, with Zn levels being higher medially. PV is low overall in these nuclei. Electron microscopic results confirmed that Zn is contained in synaptic boutons. These form asymmetrical, presumably excitatory, synapses, and the postsynaptic targets are mainly spines of projection neurons. The inhomogeneous distribution of Zn in the monkey amygdala may be related to different types or degrees of plasticity among the amygdaloid subnuclei. The complementary distribution with PV parallels that of several other substances and is interesting in the context of subnuclear vulnerability for human neuronal disease, such as seizure and Alzheimer's disease.
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PMID:Distribution of synaptic zinc in the macaque monkey amygdala. 1598 2

Dlx homeodomain transcription factors are essential during embryonic development for the production of forebrain GABAergic interneurons. Here we show that Dlx1 is also required for regulating the functional longevity of cortical and hippocampal interneurons in the adult brain. We demonstrate preferential Dlx1 expression in a subset of cortical and hippocampal interneurons which, in postnatal Dlx1 mutants, show a time-dependent reduction in number. This reduction preferentially affects calretinin(+) (bipolar cells) and somatostatin(+) subtypes (for example, bitufted cells), whereas parvalbumin(+) subpopulations (basket cells and chandelier cells) seem to be unaffected. Cell transplantation analysis demonstrates that interneuron loss reflects cell-autonomous functions of Dlx1. The decrease in the number of interneurons was associated with a reduction of GABA-mediated inhibitory postsynaptic current in neocortex and hippocampus in vitro and cortical dysrhythmia in vivo. Dlx1 mutant mice show generalized electrographic seizures and histological evidence of seizure-induced reorganization, linking the Dlx1 mutation to delayed-onset epilepsy associated with interneuron loss.
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PMID:Mice lacking Dlx1 show subtype-specific loss of interneurons, reduced inhibition and epilepsy. 1604 23

Identifying the brain regions and neuronal cell types that become active at the time of spontaneous seizures remains an important challenge for epilepsy research, and the involvement of dentate granule cells in early seizure events continues to be debated. Although Fos expression is commonly used to evaluate patterns of neuronal activation, there have been few studies of Fos localization after spontaneous seizures. Thus, in a pilocarpine model of recurrent seizures in C57BL/6 mice, Fos expression was examined at multiple time points after spontaneous seizures to follow the temporal and spatial patterns of Fos activation. By 15 min after the beginning of a spontaneous behavioral seizure, Fos labeling was evident in dentate granule cells. This labeling was particularly striking because of its wide extent and relatively uniform appearance in the granule cell layer. At later time points, from 30 min to 4 h after a spontaneous seizure, Fos labeling was also detected in interneurons within the dentate gyrus and in widespread regions of the temporal lobe. Interestingly, the timing of Fos activation appeared to differ among different types of GABAergic interneurons in the dentate gyrus, with labeling of parvalbumin neurons along the base of the granule cell layer preceding that of GABA neurons in the molecular layer. The findings in this mouse model are consistent with previous suggestions that spontaneous seizures in temporal lobe epilepsy may result from a periodic breakdown of the normal filter functions of the dentate gyrus and a resulting increase in hypersynchronous activity of dentate granule cells.
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PMID:Temporal patterns of fos expression in the dentate gyrus after spontaneous seizures in a mouse model of temporal lobe epilepsy. 1607 3

Several rodent models of cortical malformation are available for the study of cellular mechanisms associated with early-onset epilepsy, but few are associated with spontaneous seizures. We examined the effect of pilocarpine on the spontaneous seizure development and excitability of the CA1 pyramidal cells of rats after prenatal treatment with methylazoxymethanol (MAM). Pilocarpine induced status epilepticus (SE) onset latency was greater for normal rats than for MAM-treated rats. After several days of normal behavior following pilocarpine treatment, the duration of spontaneous seizures were greater in MAM-pilocarpine rats than in normal-pilocarpine rats. Compared with the normal rats, electrical stimulation of afferent fibers resulted in more robust population responses in the CA1 region in all groups. At interstimulus intervals of 30 and 70 ms, the MAM-pilocarpine rats displayed a decrease in paired pulse inhibition versus the conventional MAM rats. A loss of somatostatin- and parvalbumin-immunoreactive neurons was apparent in the normal-pilocarpine rats, MAM-pilocarpine rats, and conventional MAM rats. These results indicate that pilocarpine induces spontaneous seizures and hyperexcitability in MAM-pilocarpine rats.
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PMID:Pilocarpine-induced seizure susceptibility in rats following prenatal methylazoxymethanol treatment. 1607 84

Calcium-binding proteins (CBPs), such as parvalbumin and calbindin D-28k, are useful markers of specific neuronal types in the CNS. In recent studies, expression of CBPs may be indicative of a deactivated neuronal state, particularly epilepsy. However, it is controversial whether altered expression of CBPs in the hippocampus practically indicate neuronal activity. Therefore, the present study was performed to investigate the extent of profiles of expression of CBPs in the rat hippocampus affected by several episodes induced by electroconvulsive shock. In the present study, following electroconvulsive shock expression of CBPs were reduced in the hippocampus in a stimulus-dependent manner, and recovered to the control level at 6 h after electroconvulsive shock. However, paired-pulse responses of the dentate gyrus were transiently impaired by electroconvulsive shock, and immediately normalized to baseline value. In addition, effects of electroconvulsive shock on expression of CBPs and paired-pulse responses were prevented by pretreatment of vigabatrin. These findings suggest that reduced expression of CBPs induced by seizure activity may be indicative of hyperactivity of CBP positive neurons, which is a practical consequence of the abnormal discharge, and that they may play an important role in regulating seizure activity.
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PMID:Reduced calcium binding protein immunoreactivity induced by electroconvulsive shock indicates neuronal hyperactivity, not neuronal death or deactivation. 1622 85


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