Biomedical subjects

K Kogure

Publications and source records attributed to K Kogure.

At least 145 records · Page 8Linked to original sources

PubMed1993

Exposure to sub-lethal ischemia failed to prevent subsequent ischemic death of dentate hilar neurons, as estimated by laminin immunohistochemistry.

The CA1 pyramidal cells and dentate hilar neurons are selectively vulnerable to forebrain ischemia. Although brief ischemia induces tolerance to subsequent ischemia in the CA1 pyramidal neurons, a protective effect of preceding brief ischemia on the dentate hilar neurons has not been established. We observed that vulnerable dentate hilar neurons were strongly laminin-immunopositive and used laminin immunohistochemistry to estimate the fate of dentate hilar neurons after ischemia. Pretreatment of brief sublethal ischemia, which effectively protects the CA1 neurons, failed to prevent the death of dentate hilar neurons. These results indicate that brief ischemia failed to induce tolerance to subsequent longer ischemia in the dentate hilar neurons.

Animals↗

PubMed1993

Changes of spirodecanone binding in the gerbil hippocampus after cerebral ischaemia.

Using quantitative receptor autoradiography, spirodecanone binding was evaluated in the gerbil hippocampus 1 h-1 month after cerebral ischaemia of 10 min. The spirodecanone binding was unaffected in the hippocampus up to 48 h after ischaemia. Thereafter, increased binding was found in the stratum radiatum of hippocampal CA1 sector 7 days and 1 month after ischaemia. Other hippocampal regions showed no significant alterations in the spirodecanone binding. A histological study revealed that the hippocampal CA1 sector was severely damaged 7 days and 1 months after ischaemia. These results demonstrate that spirodecanone binding sites are located on interneurones or glial cells in the hippocampal CA1 sector.

Animals↗

PubMed1993

An immunohistochemical study of copper/zinc superoxide dismutase and manganese superoxide dismutase in rat hippocampus after transient cerebral ischemia.

We investigated the changes of copper/zinc superoxide dismutase (CuZn-SOD) and manganese superoxide dismutase (Mn-SOD) in the rat hippocampus after 10 min of cerebral ischemia induced by 4-vessel occlusion. The rats were allowed to survive for 4 h, 1 day, 3 days, and 7 days after ischemia. The distribution of SODs were determined by immunohistochemical staining with antibodies against rat CuZn-SOD and Mn-SOD. CA1 pyramidal neurons and granule cells of the dentate gyrus showed intense CuZn-SOD immunoreactivity, whereas CA3 and CA4 neurons showed weaker immunostaining than CA1 neurons in normal animals. The immunoreactivity was reduced by 4 h after ischemia in CA1, CA3, and CA4 neurons when no histological damage was observed. Mn-SOD immunostaining revealed more intense immunoreactivity in CA3 pyramidal neurons than in CA1 neurons in normal animals. Interneurons in the CA1 and CA3 regions and the dentate hilus also showed high Mn-SOD immunostaining. Although CA1 neurons lost Mn-SOD immunoreactivity by 1 day after ischemia, CA3 neurons and interneurons retained the immunoreactivity and preserved intact cell contour after ischemia. In addition, reactive glial cells, which were differentiated by immunocytochemical staining against glial fibrillary acidic protein for reactive astrocytes and histochemical staining for reactive microglial cells, were intensely stained for CuZn-SOD and Mn-SOD after ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Alterations of Ca2+ currents and their sensitivities to Ca2+ antagonists during application and after deprivation of nerve growth factor.

The alterations in morphology and Ca2+ currents (ICa) were assessed in PC12 cells, which were (1) control (untreated), (2) treated with nerve growth factor (NGF), and (3) deprived of NGF. NGF treatment induced neuronal differentiation morphologically and increased the current density of ICa, and especially that of the omega-conotoxin (omega-CgTX)-sensitive component. NGF-deprived cells manifested morphological deterioration and did not exhibit remarkable changes in the current density of the total ICa and dihydropyridine components, whereas the omega-CgTX-sensitive ICa component was decreased significantly compared with that in NGF-treated cells. The results suggest that the total function of Ca2+ channels, including the dihydropyridine component, does not seem to be lost at the initial stage of neuronal deterioration, whereas omega-CgTX-sensitive Ca2+ channels lost their function early.

Animals↗

PubMed1993

Fetal hippocampal transplants reduce aberrant mossy fiber sprouting after CA3 pyramidal cell damage.

The CA3 pyramidal cells receive mossy fibers from the dentate granule cells, and the damage to CA3 pyramidal cells induces aberrant mossy fiber sprouting near the site of normal targets. Fetal CA1 and CA3 subregions were separately transplanted into the host CA3 subfield, where CA3 pyramidal neurons were previously damaged with kainic acid. In vitro [3H]inositol 1,4,5-trisphosphate (IP3) receptor autoradiography was used to analyze the purity of CA1 neurons. CA1 transplants had high IP3 receptor density compatible with adult CA1 subfield, while CA3 transplants had trace IP3 receptors. Animals with successful graft-host connections exhibited no aberrant mossy fiber sprouting, and mossy fibers invaded into the fetal CA3 grafts. However, animals without direct host mossy fibers-grafts connection showed aberrant mossy fiber sprouting in the CA3 subfield. These observations demonstrate that aberrant mossy fiber sprouting was suppressed by molecular cues presented on the grafted neurons and that [3H]IP3 receptor autoradiography provides an excellent marker for the identification of the CA1 pyramidal cells in grafts.

Animals↗

PubMed1993

Induction of HSP90 alpha heat shock mRNA after transient global ischemia in gerbil hippocampus.

Distribution of heat shock protein (HSP) 90 alpha mRNA induction after 10 min of transient global ischemia was investigated in gerbil hippocampus by in situ hybridization. A small amount of HSP90 alpha mRNA was normally present in hippocampal cells and the mRNA was further induced with a peak at 8 h after ischemia. In hippocampal CA1 cells that are vulnerable to ischemia, HSP90 alpha mRNA was continuously induced by 1 day and finally diminished at 2 days. The temporal profile of HSP90 alpha mRNA induction in hippocampal CA1 cells was similar to that of HSP70 mRNA reported previously, suggesting a cooperative role of HSP90 alpha with other HSPs after ischemia.

Animals↗

PubMed1993

Rolipram enhances the development of voltage-dependent Ca2+ current and serotonin-induced current in rat pheochromocytoma cells.

The effects of chronic treatment (6-8 days) with a phosphodiesterase inhibitor, rolipram, on the expression of voltage-dependent Ca2+ channels, nicotinic acetylcholine (ACh) receptors and 5-hydroxytryptamine (5-HT) receptors were investigated in PC12 cells. The results were compared with the effects of nerve growth factor (NGF), 8-bromo-cyclic AMP (8-Br-cAMP) and phorbol 12-myristate 13-acetate (PMA). In the morphological study rolipram, at a high concentration (100 microM) induced the extension of neurites. A similar result was obtained in 8-Br-cAMP (1 mM)-treated cells. Rolipram, at a low concentration (10 microM) or PMA (10(-7) M) did not induce obvious morphological change. NGF (100 ng/ml) induced the extension of long neurites and the formation of neural networks. Rolipram (100 microM) increased the current density (pA/pF) of voltage dependent Ca2+ current (ICa). Both NGF and 8-Br-cAMP also increased the current density of ICa, whereas PMA did not. NGF increased the current density of the nicotinic ACh response whereas rolipram, 8-Br-cAMP and PMA decreased. Rolipram (100 microM), NGF (100 ng/ml), and 8-Br-cAMP (1 mM) increased the current density of the 5-HT response whereas the effect of PMA (100 nM) was slight. The results suggest that rolipram is able to contribute to the neuronal development by increasing intracellular cAMP as well as 8-Br-cAMP. Consequently, rolipram behaves like a neurotrophic factor in cultured PC12 cells.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1993

Immunohistochemical localization of ubiquitin in gerbil hippocampus with induced tolerance to ischemia.

Using immunohistochemistry, we visualized the localization of ubiquitin in the gerbil hippocampus following 3 min of ischemia with or without pretreatment with 2 min of sublethal ischemia and 3 days of reperfusion. Ubiquitin immunoreactivity in the hippocampus disappeared 4 h after 3 min of ischemia both with and without pretreatment. The immunoreactivity in the CA3 and the dentate gyrus recovered by 24 h, but never recovered in the CA1, where delayed neuronal death takes place, without pretreatment. However, the pretreatment, which protects against CA1 neuronal damage, led to recovery of ubiquitin immunoreactivity in the CA1 by 48 h. Thus, recovery of ubiquitin may be a prerequisite to neuronal survival after ischemia and the role of ubiquitin in ischemic tolerance was suggested.

Animals↗

PubMed1993

Effect of pentobarbital on postischemic SCH 23390 and rolipram binding in gerbil brain.

We investigated the postischemic alterations in dopamine D1 receptor and Ca2+/calmodulin independent cyclic adenosine monophosphate (cyclic AMP) selective phosphodiesterase in gerbils and examined the effect of pentobarbital on these alterations. [3H]SCH 23390 and [3H]rolipram, respectively, were used to label dopamine D1 receptor and Ca2+/calmodulin independent cyclic-AMP selective phosphodiesterase. Transient cerebral ischemia was induced for 10 min, and pentobarbital (40 mg/kg) was administered intraperitoneally 30 min prior to ischemia. 5 h after ischemia, [3H]rolipram binding decreased significantly in the striatum and hippocampus, whereas no significant change was found in [3H]SCH 23390 binding. 7 days after ischemia, however, there was a marked reduction in both [3H]SCH 23390 and [3H]rolipram binding in the striatum and hippocampus, where histological neuronal damage was found. Pentobarbital significantly ameliorated postischemic decreases in [3H]rolipram binding both 5 h and 7 days after recirculation in most areas studied. Furthermore, this drug significantly prevented postischemic reduction in [3H]SCH 23390 binding (only) 7 days after ischemia. These results suggest that alteration of cyclic AMP selective phosphodiesterase is more sensitive at an earlier stage after ischemic insult than that of dopamine D1 receptors. Our results also demonstrate that pentobarbital reduces the alteration in [3H]SCH 23390 and [3H]rolipram binding after cerebral ischemia.

Animals↗

PubMed1993

Correlation between electroconvulsive seizure and HSC70 mRNA induction in mice brain.

The effects of electroconvulsive seizure and anti-convulsant drugs on induction of mRNA of heat shock protein were studied in mouse brain. Electrical shock induced mRNA of heat shock cognate protein (HSC70), but not heat shock protein (HSP70) mRNA. The induction was maximum 1 h after the ECS and continued for several hours, followed by long-lasting depression. Diazepam slightly prevented the ECS, but strongly attenuated the induction of HSC70 mRNA. Whereas phenytoin, which blocked the seizure, did not decrease but delayed the induction of HSC70 mRNA. The present results suggest that HSC70 mRNA level is increased with the ECS and that the induction level did not necessarily correlate the severity of the seizure.

Animals↗

PubMed1993

Immunohistochemical visualization of heat shock protein-70 in the gerbil hippocampus following repeated brief cerebral ischemia.

Recent experiments have shown that neuronal damage following repeated cerebral ischemic insults is more extensive than the damage after a single equivalent period of ischemia. To clarify the mechanism of this cumulative neuronal damage after repeated ischemia, we visualized the localization of heat shock protein-70 (HSP70), a marker of neuronal stress, with immunohistochemistry using a monoclonal antibody. Mongolian gerbils were subjected to three 2-min forebrain ischemic insults spaced at 1-h intervals and to a single 6-min period of ischemia. The animals were killed 24 and 48 h after ischemia. Hippocampal CA1 pyramidal neurons, which are destined to die, showed no HSP70 staining 24 and 48 h after three 2-min ischemic insults, but showed a mild to moderate staining after 6 min of ischemia, suggesting more severe damage after repeated ischemia. CA3 neurons, which are resistant to ischemia, were intensely stained with HSP70 antibody following 6 min of ischemia but was stained only slightly after three 2-min ischemic insults, showing less stress after repeated ischemia. Thus, thresholds for cell damage are obviously different among different cell populations within the hippocampus; the different neuronal populations respond differently to single and repetitive ischemia. The result suggests that cumulative neuronal damage after repeated sublethal ischemic insults is produced by increased susceptibility to subsequent insults when ischemic stress reaches certain thresholds that are different among different neuronal populations.

Animals↗

PubMed1993

A comparison of induced heat-shock protein in neurons destined to survive and those destined to die after transient ischemia in rats.

We examined the induction of heat-shock protein (HSP) in CA-1 pyramidal neurons compared with that in CA-3 pyramidal neurons, in rat brain following 20 min of ischemia. The time course of the changes of localization of HSP was investigated using immunohistochemical and Western blot analyses. The induction of HSP in the CA-1 subfield was the same as that in the surviving hippocampal CA-3 subfield.

Animals↗

PubMed1993

The preconditioned hippocampus accelerates HSP70 heat shock gene expression following transient ischemia in the gerbil.

To evaluate the mechanism of tolerance for ischemia, inductions of heat shock protein (HSP) 70 mRNA and immunoreactive HSP70 protein were studied in the preconditioned gerbil hippocampus. Following the single 3.5-min ischemia, HSP70 mRNA was induced in all hippocampal cells. However, the hippocampal CA1 cells produced only a minimum HSP70 protein, and the cells were almost lost by 7 days. Following the 3.5-min ischemia after 2-min pretreatment, the CA1 cells produced a strong immunoreactive HSP70 signal and large populations of the CA1 cells survived at 7 days. The peak time of the HSP70 mRNA induction shifted to earlier period of reperfusion in the CA1 cells as compared to the case with single ischemia. This accelerated change of HSP70 expression could play an important role for the acquisition of ischemic tolerance of the hippocampal CA1 neurons.

Adaptation, Physiological↗

PubMed1993

Reduction of HSP70 and HSC70 mRNA inductions by bifemelane hydrochloride after transient ischemia in gerbil brain.

The effect of bifemelane hydrochloride (BFH) on the induction of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNAs after transient global ischemia in gerbil brain was investigated by in situ hybridization using cloned cDNA probes selective for each mRNA species. Following 3.5 min of ischemia, HSP70 and HSC70 mRNAs were induced in all hippocampal cells. The CA1 cells were almost lost by 7 days. Treatment with BFH twice before and after ischemia (total 60 mg/kg, i.p.) reduced the induction of HSP70 and HSC70 mRNAs both at 8 h and 1 day of the reperfusion, and about half of the CA1 cells survived at 7 days. Thus, the reduction of HSP70 and HSC70 mRNA inductions after ischemia may suggest that BFH reduced intra- and/or post-ischemic stress, and protected CA1 cells from ischemic damage.

Animals↗

PubMed1993

Regional difference of HSP70 and HSC70 heat shock mRNA inductions in rat hippocampus after transient global ischemia.

Induction of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNAs, and immunoreactivity for HSP70 were investigated in rat hippocampus after transient global ischemia with in situ hybridization and immunohistochemistry. In sham control brain, HSP70 mRNA was scarcely present, while HSC70 mRNA was expressed in most neuronal cells. After 20 min of transient four-vessel occlusion (4VO), ischemia-resistant hippocampal CA3 cells consistently induced HSP70 mRNA along with further HSC70 mRNA. The resistant dentate granule (DG) cells continuously induced HSC70 mRNA even after the great reduction of HSP70 mRNA. In contrast, in ischemia-vulnerable CA1 cells, a relatively lower level of HSC70 mRNA induction than the level of HSP70 mRNA induction was observed. The vulnerable CA1 cells produced a prominent HSP70 immunoreactivity. These results suggest that the vulnerability of the CA1 cells after transient ischemia may not be explained only by the ability of HSP70 induction, but may be related to the imbalance of HSP70 and HSC70 mRNA inductions.

Animals↗

PubMed1993

Early disturbance of a mitochondrial DNA expression in gerbil hippocampus after transient forebrain ischemia.

The level of mRNA for cytochrome c oxidase subunit I (COX-I), which is encoded by mitochondrial DNA (mtDNA), progressively decreased in the hippocampal CA1 neurons of gerbils from 1-3 h of the reperfusion after 3.5 min of transient forebrain ischemia, and completely disappeared at 7 days. The activity of cytochrome c oxidase (COX) protein also showed the early decrease in the CA1 cells, and was followed by the reduction of the level of COX-I DNA after 2 days. However, the activity of succinic dehydrogenase (SDH), a mitochondrial enzyme that is encoded by nuclear DNA, maintained normal activity until 1 day in the CA1 cells, and significantly decreased at 7 days. These results suggest that the early onset and the progressive disturbance of a mitochondrial DNA expression found selectively in the CA1 neurons could cause progressive failure of energy production of the cells that eventually results in the neuronal cell death.

Animals↗

PubMed1993

Evolution of the type II hexokinase gene by duplication and fusion of the glucokinase gene with conservation of its organization.

The type I, II, and III isozymes of mammalian hexokinase (100 kDa) all consist of a duplicated, highly homologous peptide sequence, each half of which is very similar to that of glucokinase (type IV hexokinase, 50 kDa) and yeast hexokinase (50 kDa). We isolated a genomic clone of type II hexokinase that contained five exons encoding the C-terminal region of type II hexokinase. The positions of intron insertions of the isolated clone were found to be identical with those of the glucokinase gene, indicating that the type II hexokinase gene arose from the glucokinase gene. Furthermore, we prepared two DNA fragments of the type II hexokinase gene amplified from total genomic DNA. The exons in these fragments were found to be constructed by linkage of the coding region of the last exon and second exon of the glucokinase gene, indicating that the hexokinase gene arose by fusion of two glucokinase genes. These results clearly show that the mammalian hexokinase gene evolved from the glucokinase gene by gene duplication and fusion with conservation of the gene organization.

Amino Acid Sequence↗

PubMed1993

Behavioral and histological changes after repeated brief cerebral ischemia by carotid artery occlusion in gerbils.

The effects of repeated brief episodes of cerebral ischemia on passive avoidance learning and hippocampal neuronal degeneration were investigated in gerbils. Latency of step-through was shortened for the entire 7-day period when gerbils were trained at day 3 after 3 episodes of carotid artery occlusion for 2 min each at 60-min intervals. In addition, latency of passive avoidance was shortened for 63 days when gerbils were retrained at 14 days after occlusion. Severe neuronal degeneration in the CA1 regions of the hippocampus was observed 4 and 17 days after occlusion. A close correlation was seen between latency in the passive avoidance response and neurological degeneration of the hippocampal CA1 region. This fact was strongly supported by the results of another experiment that 1 2-min occlusion with almost no neuronal degeneration did not affect learning behavior while 3 1-min occlusions showed neuronal death and impairment of learning behavior of a moderate degree 4 days after occlusion. These results suggest that this gerbil model with carotid artery occlusion is useful for the quantitative measurement of functional changes in the chronic phase of repeated cerebral ischemia.

Animals↗