Enhanced glial fibrillary acidic protein-delta expression in human astrocytic tumor.

Astrocytic tumor is one of the most common primary tumors of the adult brain. Although there are several biochemical markers for the categorization of astrocytic tumor, few markers are used for histopathological diagnosis. Therefore, we evaluated glial fibrillary acidic protein (GFAP)-delta, a product of alternative splicing variants of GFAP-alpha, as a diagnostic marker.

Pyridoxal-5'-phosphate phosphatase/chronophin inhibits long-term potentiation induction in the rat dentate gyrus.

Pyridoxal-5'-phosphate (PLP)-phosphatase/chronophin (PLPP/CIN) directly dephosphorylates actin-depolymerizing factor (ADF)/cofilin as well as PLP. Although PLPP/CIN plays a role in the regulation of F-actin and vitamin B(6) metabolism, there is no direct evidence to support a correlation between PLPP/CIN and F-actin polymerization during long-term potentiation (LTP) induction. In this study, we investigated whether the expression of PLPP/CIN is altered following LTP induction, and whether Tat-PLPP/CIN transduction affects LTP induction in the rat dentate gyrus (DG).

Upregulated TWIK-related acid-sensitive K+ channel-2 in neurons and perivascular astrocytes in the hippocampus of experimental temporal lobe epilepsy.

Purpose: To identify the modulation of Tandem of P-domains in a weak inwardly rectifying K(+) channel (TWIK)-related acid-sensitive K(+) (TASK)-2 channel expressions in epilepsy, we conducted a comparative analysis of TASK-2 channel immunoreactivity in the hippocampus of a pilocarpine-induced rat epilepsy model.

Methods: We performed and immunohistochemical study for TASK-2 and double immunofluorescent staining for TASK-2 and glial fibrillary acidic protein (GFAP) in the rat hippocampus of pilocarpine-induced epilepsy models.

Results: In control animals, TASK-2 immunoreactivity was strongly detected in CA1-3 pyramidal layers and dentate granule cell layer.

Age-dependent pathogenesis of murine gammaherpesvirus 68 infection of the central nervous system.

Gammaherpesvirus infection of the central nervous system (CNS) has been linked to various neurological diseases, including meningitis, encephalitis, and multiple sclerosis. However, little is known about the interactions between the virus and the CNS in vitro or in vivo. Murine gammaherpesvirus 68 (MHV-68 or (gamma)HV-68) is genetically related and biologically similar to human gammaherpesviruses, thereby providing a tractable animal model system in which to study both viral pathogenesis and replication.

Blockade of P2X receptor prevents astroglial death in the dentate gyrus following pilocarpine-induced status epilepticus.

Objective: The P(2) receptor is involved in diverse signal cascades, including the initiation of the rapid release and processing of proinflammatory cytokines, the induction of cytoskeletal rearrangements and transcription factor activation. Therefore, we investigated whether blocking the P(2) receptor would prevent the astroglial death induced by status epilepticus (SE).

Methods: We performed seizure induction and drug treatments.

The expression of somatostatin receptors in the hippocampus of pilocarpine-induced rat epilepsy model.

During the course of this study, we sought examine whether the expression of somatostatin receptors (SSTRs) is altered in the hippocampus following pilocarpine-induced status epilepticus (SE) in order to understand the role/function of SSTRs in the hippocampus after epileptogenic insults. SSTR1 and SSTR4 immunoreactivities were increased in the hippocampus at 1 week after SE. At 4 weeks after SE, SRIF1-family (SSTR 2A, SSTR2B, and SSTR5) immunoreactivity was increased only in neuropil.

Spatiotemporal characteristics of astroglial death in the rat hippocampo-entorhinal complex following pilocarpine-induced status epilepticus.

Recently we reported that astroglial loss and subsequent gliogenesis in the dentate gyrus play a role in epileptogenesis following pilocarpine-induced status epilepticus (SE). In the present study we investigated whether astroglial damages in the hippocampo-entorhinal complex following SE are relevant to pathological or electrophysiological properties of temporal lobe epilepsy. Astroglial loss/damage was observed in the entorhinal cortex and the CA1 region at 4 weeks and 8 weeks after SE, respectively.

Pyridoxine 5'-phosphate oxidase, not pyridoxal kinase, involves in long-term potentiation induction in the rat dentate gyrus.

In this study, we investigated whether the expression of pyridoxal kinase (PLK) and pyridoxine-5'-phosphate oxidase (PNPO) are altered following long-term potentiation (LTP) induction, and whether Tat-PLK and Tat-PNPO transductions affect LTP induction and paired-pulse responses in the rat dentate gyrus (DG). PNPO immunoreactivity was markedly increased in dentate granule cells after the induction of LTP, but that of PLK was not. Tat-PNPO (20 and 200 microg/kg), but not Tat-PLK or vitamin B6 precursors, treatments, increased the efficiency of high frequency stimulus-induced potentiation of populations spike amplitude when compared with saline-, or Tat-protein-treated animals.

Region-specific alterations in astroglial TWIK-related acid-sensitive K+-1 channel immunoreactivity in the rat hippocampal complex following pilocarpine-induced status epilepticus.

In the present study, we performed an analysis of tandem of P domains in a weak inwardly rectifying K+ channel (TWIK)-related acid-sensitive K+ (TASK)-1 channel immunoreactivity in the rat hippocampal complex following pilocarpine-induced status epilepticus (SE). In control animals, TASK-1 immunoreactivity was strongly detected in astrocytes in the hippocampal complex. One day after SE, TASK-1 immunoreactivity in astrocytes was markedly reduced only in the molecular layer of the dentate gyrus.

Hyperthermic seizure induces persistent alteration in excitability of the dentate gyrus in immature rats.

Febrile seizure (FS) is the most common type of seizure that occurs during early childhood. It has been proposed that atypical FS (prolonged, multiple, or lateralized) results in the development of recurrent complex partial seizures accompanied by Ammon's horn sclerosis or mesial temporal sclerosis, which is the most common of the intractable epilepsy. To elucidate the characteristics of epileptogenesis or acquired epilepsy following FS, we performed prospective long-term studies using hyperthermia-induced seizure model.

Voltage-gated Na+ channel II immunoreactivity is selectively up-regulated in hippocampal interneurons of seizure sensitive gerbils.

In the present study, we investigated the distribution of voltage-gated Na(+) channels (VGSCs) in the normal and epileptic hippocampus of gerbils (a genetic epilepsy model) in order to confirm the relationship between VGSC and seizure activity in these animals. There was no difference of VGSC I immunoreactivity in the hippocampus between seizure-resistant (SR) and seizure sensitive (SS) gerbils. VGSC II immunoreactivity was rarely detected in the perikarya of principal neurons and interneurons in the SR gerbil hippocampus.

Anticonvulsant characteristics of pyridoxyl-gamma-aminobutyrate, PL-GABA.

GABA is the major inhibitory neurotransmitter in the central nervous system, and its concentration in the brain in associated with a variety of neurological disorders, including seizures, convulsions, and epilepsy. The concentration of GABA is modulated by the pyridoxal-5'-phosphate (PLP)-dependent enzymes, GAD and GABA-T. In this study, we generated pyridoxyl-gamma-aminobutyrate (PL-GABA), a novel GABA analogue composed of pyridoxyl and GABA, and have also characterized its anticonvulsant and pharmacological functions in vitro.

Potential role of pyridoxal-5'-phosphate phosphatase/chronopin in epilepsy.

Changes in actin dynamics and pyridoxal-5'-phosphate (PLP) metabolisms are closely related to the pathophysiological profiles of the epileptic hippocampus. Recently, it has been reported that PLP phosphatase/chronophin (PLPP/CIN) directly dephosphorylates actin-depolymerizing factor (ADF)/cofilin as well as PLP. In the present study, therefore, we have investigated whether PLPP/CIN is linked to the dynamics of actin filament assembly and the excitability in the rat hippocampus.

Up-regulated astroglial TWIK-related acid-sensitive K+ channel-1 (TASK-1) in the hippocampus of seizure-sensitive gerbils: a target of anti-epileptic drugs.

In order to identify the modulation of TASK (TWIK-related Acid-Sensitive K(+)) channel expressions in epilepsy, we conducted a comparative analysis of TASK channel immunoreactivities in the hippocampus of seizure-resistant (SR) and seizure-sensitive (SS) gerbils. There was no difference of the TASK-1 and TASK-2 channel expressions in the hippocampi of young SR and SS gerbils (1-2 months old). In adult SS gerbil hippocampus, TASK-1 immunoreactivity in astrocytes was higher than that in adult SR gerbil hippocampus.

Seizure activity selectively reduces 5-HT1A receptor immunoreactivity in CA1 interneurons in the hippocampus of seizure-prone gerbils.

Since the correlation between the serotonin (5-hydroxytryptamine, 5-HT) system and seizure activity remains to be clarified, we investigated the 5-HT system in the hippocampus of seizure-resistant (SR) and seizure-sensitive (SS) gerbils. There was no difference of the 5-HT system in the hippocampi of young animals (predisposed and juvenile gerbils) in both SR and SS gerbils. 5-HT immunoreactivity in the dorsal raphe nucleus and the median raphe nucleus was also similarly detected in both animal groups.

Seizure activity affects neuroglial Kv1 channel immunoreactivities in the gerbil hippocampus.

In order to confirm the species-specific distribution of voltage-gated K(+) (Kv) channels and the definitive relationship between their immunoreactivities and seizure activity, we investigated Kv1 channel immunoreactivities in the hippocampus of seizure resistant (SR) and seizure sensitive (SS) gerbils. There was distinct difference of the Kv1 channel subtypes immunoreactivity in the hippocampi in both SR and SS gerbils. Kv1.

Up-regulation of P/Q-type voltage-gated Ca2+ channel immunoreactivity within parvalbumin positive neurons in the rat hippocampus following status epilepticus.

To identify the roles of VGCC subtypes in damages/impairs of inhibitory transmission during epileptogenesis, we investigated temporal- and spatial-specific alterations in voltage-gated Ca(2+) channel (VGCC) immunoreactivities within parvalbumin (PV, a Ca(2+) binding protein) positive neurons in the rat hippocampus following status epilepticus (SE). Compared to controls, only P/Q-type (alpha1A) VGCC immunoreactivity was enhanced in PV positive neurons at the early point following SE. The alteration in P/Q-type (alpha1A) VGCC immunoreactivity showed an inverse proportionality to that in PV immunoreactivity in the dentate gyrus and the CA1 region.

The co-treatments of vigabatrin and P2X receptor antagonists protect ischemic neuronal cell death in the gerbil hippocampus.

During transient global ischemia, the excessive accumulation of intracellular Ca2+ induced by several episodes triggers delayed neuronal death within the vulnerable CA1 region of the hippocampus after ischemia-reperfusion insults. Although P2X receptors provide an additional source of Ca2+ entry, little data are available that these receptors could modulate the performance of the ischemic neuronal death. Therefore, we investigated the roles of the P2X receptor in the ischemic neuronal damage associated with various sequelae of transient ischemia, and the effects of their antagonist on the ischemic insults.

Differential paired-pulse responses between the CA1 region and the dentate gyrus are related to altered CLC-2 immunoreactivity in the pilocarpine-induced rat epilepsy model.

The epileptic hippocampus shows differential paired-pulse responses between the dentate gyrus and the CA1 region. However, little data are available to explain this phenomenon. In the present study, we identified the relationship between regional differences of paired-pulse response and voltage gated Cl(-) channel 2 (CLC-2)/vesicular GABA transport (VGAT) expression in a pilocarpine-induced rat model.

The selective effects of somatostatin- and GABA-mediated transmissions on voltage gated Ca2+ channel immunoreactivity in the gerbil hippocampus.

To identify whether altered expressions of voltage gated Ca(2+) channel (VGCC) are linked to inhibitory transmission abnormalities in the gerbil hippocampus, we investigated the effects of GABA receptor or somatostatin receptor (SST) antagonists/agonists on VGCC immunoreactivity in vivo. VGCC immunoreactivities in the hippocampus were significantly higher in seizure sensitive (SS) gerbils than in seizure resistant (SR) gerbils. P/Q-type VGCC immunoreactivity in the gerbil hippocampus was reduced by enhancement in GABA(A) and GABA(B) receptor-mediated transmission, but not by SST-mediated transmission.

Epileptogenic roles of astroglial death and regeneration in the dentate gyrus of experimental temporal lobe epilepsy.

Recent studies have demonstrated that blockade of neuronal death in the hippocampus cannot prevent epileptogenesis in various epileptic models. These reports indicate that neurodegeneration alone is insufficient to cause epilepsy, and that the role of astrocytes in epileptogenesis should be reconsidered. Therefore, the present study was designed to elucidate whether altered morphological organization or the functionalities of astrocytes induced by status epilepticus (SE) is responsible for epileptogenesis.

Altered expression of K+ -Cl- cotransporters affects fast paired-pulse inhibition during GABA receptor activation in the gerbil hippocampus.

K+ -Cl- cotransporter (KCC) plays an important role in maintaining neuronal activity. However, the effect of seizure activity or pharmacological manipulation of GABAergic transmission on KCC expression remains to be clarified. Therefore, the present study was performed to investigate whether seizure activity or GABA receptor agonist treatment changes KCC expression in the gerbil hippocampus.

The effect of P2X receptor activity on GABAA receptor-mediated inhibition in the gerbil hippocampus.

In the present study, to elucidate the effect of altered P(2)X receptor transmission on GABA(A) receptor expression and its transmission, we studied the morphological and electrophysiological responses of GABA(A) receptor in the gerbil hippocampus following P(2)X receptor antagonist/agonist treatment. Suramin or pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) treatment did not affect GABA(A) receptor immunoreactivities and paired-pulse responses in the gerbil hippocampus. In addition, ATP treatment did not significantly affect population spike amplitude ratios and EPSP slope ratios in the gerbil dentate gyrus.

The effect of topiramate on GABA(B) receptor, vesicular GABA transporter and paired-pulse inhibition in the gerbil hippocampus.

To extend our understanding of the properties of topiramate (TPM), we investigated the effect of TPM on GABAergic transmission in the dentate gyrus of gerbil. TPM treatment (> or = 40 mg/kg) dramatically decreased GABA(B)R2, not GABA(B)R1, immunoreactivity in hilar interneurons. In contrast, TPM treatment increased vesicular GABA transporter immunoreactivity and the paired-pulse inhibition in the dentate gyrus of seizure prone gerbils.

Differential effects of vigabatrin and zonisamide on the neuropeptide Y system in the hippocampus of seizure prone gerbil.

Changed neuropeptide Y (NPY) system in the hippocampus has been reported in various experimental epileptic models. However, there have been little data concerning the alteration in the NPY system in the epileptic hippocampus following treatment of anti-epileptic drugs (AEDs). In the present study, therefore, we performed analyses of effects of vigabatrin (VGB) and zonisamide (ZNS) treatment on the NPY system in the hippocampus of the seizure sensitive (SS) gerbils.