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Biomedical subjects

M Asanuma

Publications and source records attributed to M Asanuma.

At least 73 records · Page 4Linked to original sources
PubMed1995

High DNA-binding activity of transcription factor NF-kappa B in synovial membranes of patients with rheumatoid arthritis.

Our objective was to clarify the DNA-binding activity of transcription factor NF-kappa B as related to cytokine induction in the synovium of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Synovial membranes were obtained during arthroplasty of the knee from 7 patients with RA and 4 patients with OA. Nuclear extracts obtained from the synovial membranes were examined by electrophoretic mobility shift assay to determine the DNA-binding activity of NF-kappa B. Markedly high DNA-binding activity of NF-kappa B was detected in the synovial membranes of RA patients, while virtually no activity was observed in those of OA patients. These results suggest that the high induction of NF-kappa B in the nuclear extracts may be relatively specific to synovial membranes in RA. NF-kappa B may regulate the production of cytokines at the site of synovial inflammation.

Aged↗
PubMed1994

Reduced choline acetyltransferase activity and muscarinic M1 receptor levels in aged Fisher 344 rat brains did not parallel their respective mRNA levels.

Differences in the acetylcholine (ACh)-mediated neuronal system of the brain between aged and young rats were studied by measuring choline acetyltransferase (ChAT) activity, muscarinic M1 receptor (M1-R) and their respective mRNA levels. In aged rats, ChAT activity and the M1-R level were significantly reduced in the cerebral cortex, hippocampus and striatum compared with that in young rats. On the other hand, there was no difference in the ChAT mRNA level in the striatum and the basal forebrain, or the M1-R mRNA level in the cerebral cortex, hippocampus and striatum between aged and young rats. The effects of chronic administration of bifemelane (4-(2-benzylphenoxy)-N-methylbutylamine hydrochloride), which is used for the treatment of sequelae of cerebrovascular diseases, were also evaluated. In aged rats chronically administered bifemelane, the ChAT activity recovered to the level in the young rats in the cerebral cortex and hippocampus, and the M1-R level recovered completely in the cerebral cortex, hippocampus and striatum. However, the ChAT mRNA level and the M1-R mRNA level were not affected by bifemelane administration. Thus, the decreases and recoveries in ChAT activity and M1-R level did not parallel the changes in their respective mRNAs. These results suggest that the age-related impairments in ACh-mediated neuronal system are considered to be caused primarily by disorders of post-transcriptional events.

Aging↗
PubMed1994

Bromocriptine protects mice against 6-hydroxydopamine and scavenges hydroxyl free radicals in vitro.

Pretreatment with bromocriptine (5 mg/kg, i.p., 7 days) completely protected against the decrease in mouse striatal dopamine and its metabolites induced by intraventricular injection of 6-hydroxydopamine after intraperitoneal administration of desipramine, but similar pretreatment with L-DOPA/carbidopa (75/7.5 mg/kg, i.p., 7 days) showed only partial protective effect. Furthermore, in an in vitro system that generated.OH from FeSO4-H2O2, bromocriptine dose-dependently reduced the number of .OH radicals. These findings indicate that bromocriptine has a neuroprotective effect against neurotoxins such as 6-hydroxydopamine, probably due, in part, to its hydroxyl radical scavenging activity and inhibiting effect on dopamine turnover rate. This suggests that early introduction of bromocriptine in the therapy of Parkinson's disease may be superior to treatment with L-DOPA alone.

Animals↗
PubMed1994

Changes in lipid peroxidation, Cu/Zn-superoxide dismutase and its mRNA following an intracerebroventricular injection of 6-hydroxydopamine in mice.

A single i.c.v. injection of 6-hydroxydopamine (6-OHDA) in mice resulted in a biphasic increase in lipid peroxidation as assayed by the level of thiobarbituric acid-reacting substances (TBARS). An increase in Cu/Zn-superoxide dismutase (SOD) activity was temporally related with the first peak of TBARS but remained unchanged during the second TBARS peak. This suggests that a free radical species other than O2- may be involved in the late onset increase in TBARS. The level of Cu/Zn-SOD mRNA did not immediately reflect the change in Cu/Zn-SOD activity but rather increased gradually reaching significantly higher levels only 8 weeks after i.c.v. an injection of 6-OHDA. This increase in Cu/Zn-SOD mRNA likely occurs in response to a consumption of intrinsic SOD. Thus, short- and long-term increases in lipid peroxidation likely occur by different mechanisms and studies of both are needed to elucidate the neurodegenerative process.

Animals↗
PubMed1994

Differential effects of chronic L-dopa treatment on lipid peroxidation in the mouse brain with or without pretreatment with 6-hydroxydopamine.

Whether or not chronic L-dopa treatment (100 mg/kg, intraperitoneally (i.p.), twice daily for 4 weeks) alters lipid peroxidation in the brain as an indicator of neuronal damage was examined in normal mice and mice in which catecholamine (CA) neurons had been injured previously by the administration of 6-hydroxydopamine (6-OHDA), followed by recovery. In normal mice, chronic L-dopa treatment reduced the thiobarbituric acid reacting substances (TBARS) level, an indicator of lipid peroxidation, in the cerebral cortex. In contrast, in mice with CA neuronal injury induced by pretreatment with 6-OHDA, the chronic L-dopa treatment markedly increased the TBARS in the striatum and frontal cortex, despite recovery of the striatal dopamine levels similar to those in the control mice. These findings suggest that the long-term high-dose administration of L-dopa enhances the progression of neuronal damage in patients with injured CA neurons such as those with Parkinson's disease.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Effect of vagotomy on hyperactivity and increased dopamine turnover induced by intraperitoneal administration of thyrotropin-releasing hormone.

Thyrotropin-releasing hormone (TRH) injected intraperitoneally at doses of 10 mg/kg and 20 mg/kg induced marked hyperactivity in rats. Although regional levels of brain dopamine and its metabolites (DOPAC and HVA) in vagotomized rats did not differ from those in sham-operated controls, the (DOPAC + HVA)/dopamine ratio, an indicator of dopamine turnover, was significantly higher in the nucleus accumbens of TRH-treated sham-operated rats than that in untreated sham-operated controls. TRH injection induced hyperactivity only in sham-operated rats and not in subdiaphragmatic bilaterally vagotomized rats. Similarly, bilateral vagotomy completely abolished the TRH-induced increases in dopaminergic turnover in the nucleus accumbens. These results suggest that the dopaminergic system in the nucleus accumbens is involved in hyperactivity induced by TRH, and that TRH mainly affects peripheral receptors. The vagal nerve may be the major pathway from the visceral organs to the brain involved in the etiology of hyperactivity.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Acetylcholinesterase inhibitor ENA-713 protects against ischemia-induced decrease in pre- and postsynaptic cholinergic indices in the gerbil brain following transient ischemia.

The effects of pre-treatment with ENA-713, an acetylcholinesterase (AChE) inhibitor, on changes in pre- and postsynaptic cholinergic indices in gerbil brain following transient ischemia were studied at 4 and 14 days after recirculation. In the ischemic group, hippocampal acetylcholine (ACh) level was significantly reduced (to 23% of sham-operated controls) at 4 days post-ischemia, but this reduction was completely prevented by ENA-713 treatment. Choline acetyltransferase (ChAT) and cholinesterase (ChE) activities were not significantly changed at 4 and 14 days post-ischemia. Although the maximum number (Bmax) of muscarinic ACh receptor (mACh-R) binding in the hippocampus was decreased (to 44%) without any change in affinity at 14 days post-ischemia, this decrease was also inhibited by ENA-713 treatment. In addition, histological experiment indicated that ENA-713 inhibited ischemia-induced pyramidal cell loss in the hippocampal CA1 regions. Thus, these findings suggest that ENA-713 has protective, neurotrophic and therapeutic effects on cerebrovascular type dementia due to cerebral ischemia.

Acetylcholine↗
PubMed1994

[Involvement of immune mechanism in the progressive brain damage].

No definitive evidence for the participation of the immune system in progressive brain damage has been previously reported. However, glial cells continue to accumulate after degeneration of neurons appears to be completed, and a recent study showed that microglia and leukocytes also accumulate after brain damage. Thus, it seemed possible that immune responses might play a role in the delayed effects. Cyclosporin A (CsA) is a cyclic undecapeptide of fungal origin with a strong immunosuppressive action but low myelotoxicity. We examined the effect of CsA administration on three different kinds of animal models for neurological deficits. Late onset reduction of muscarinic receptors after transient forebrain ischemia in gerbils was prevented by daily post-ischemic administration of CsA. This indicates that an immune mechanism may be involved in the progressive brain damage occurring after transient ischemia. On the other hand, CsA exacerbated iminodipropionitrile-induced dyskinesia both behaviorally and biochemically. CsA also mimicked pentylenetetrazol-induced seizures. These findings suggest that immune mechanisms may play important roles in the progression of brain damage and possibly that immunosuppressants might open a new chapter in the pathophysiology and treatment of chronic progressive neurodegenerative diseases. Further investigations on the immune response in the progressive brain damage are needed.

Animals↗
PubMed1994

Regional changes in alpha-tubulin and beta-actin mRNA accumulations after transient ischemia in spontaneously hypertensive rat brains.

Regional changes in the mRNA accumulations for cytoskeletal proteins alpha-tubulin and beta-actin were examined by in situ hybridization and Northern blot analysis in spontaneously hypertensive rat brains at chronic stages after 3 hours of transient ischemia. alpha-Tubulin mRNA accumulations showed no significant change at 2 weeks after transient ischemia except for a significant decrease in the frontal cortex (9.7%, p < 0.01) coinciding with ischemia induced histological changes. beta-Actin mRNA level was significantly increased in the parietal cortex (8.5%), septum (10.0%), amygdala (11.0%), CA4 area (5.8%) and the dentate gyrus (7.5%) of the hippocampus at 2 weeks after recirculation compared with a sham-operated control group (p < 0.01). The ischemic areas of hippocampal and frontocortical lesions receive afferent neurons from those regions where beta-actin mRNA was increased, suggesting that ischemia-induced increases in beta-actin mRNA may reflect actin synthesis in these neurons to compensate for lost synaptic connections. Two cytoskeletal mRNA concentrations reacted differently to cerebral ischemia, and did not parallel histological signs of ischemia either temporally or spatially.

Actins↗
PubMed1993

The preventive effect of cyclosporin A, an immunosuppressant, on the late onset reduction of muscarinic acetylcholine receptors in gerbil hippocampus after transient forebrain ischemia.

We previously reported that a late onset reduction of muscarinic acetylcholine receptors (LORMAR) occurs in the gerbil hippocampus after 5 min of transient ischemia. This reduction begins as late as 7 days post-ischemia and accompanies the accumulation of glia, but is subsequent to completion of the disappearance of CA1 pyramidal cells. In the present study, we showed that this LORMAR was prevented by daily post-ischemic administration of the immunosuppressant cyclosporin A (CsA). The effectiveness of CsA against the LORMAR indicates that an immune mechanism may be involved in the progressive brain damage occurring after transient ischemia.

Animals↗
PubMed1993

Effect of chronic ceruletide treatment on dopaminergic neurotransmitters, receptors and their mRNAs in the striatum of rats with dyskinesia induced by iminodipropionitrile.

To clarify the mechanism of long-lasting ceruletide action, an analogue of cholecystokinin, in relieving the dyskinesia induced by the iminodipropionitrile (IDPN), we investigated the changes in dopaminergic neuronal system in the striatum. In the control rats, ceruletide had no significant effect on the concentrations of dopamine (DA), DOPAC or HVA or on the turnover of DA in the striatum. The concentration of DA was decreased and the turnover of DA [(DOPAC + HVA)/DA] was increased in the striatum of IDPN-treated rats. Chronic administration of ceruletide (160 micrograms.kg-1.day-1 x 10 days) increased DA concentration and decreased DA turnover only transiently. Both D1 and D2 receptors and their mRNAs were decreased in the striatum of rats given IDPN. After chronic ceruletide treatment, D1 receptor rose to the control level for 3 days, while the D2 receptor rose to a level 1.5 times the control level for 3 days. Even at the 7 days after chronic ceruletide treatment, D2-R rose significantly as compared with the IDPN-treated rats. Both D1 and D2 receptor mRNAs were significantly increased for 3 days in the IDPN-treated rats. These observations indicate that the synthesis of DA receptors is increased by ceruletide treatment in the striatum of IDPN-treated rats. These changes in DA receptors and their mRNAs closely paralleled the changes in dyskinetic movement of the IDPN-treated rats after repeated daily administration of ceruletide, as previously reported. The parallel changes between the DA receptors and dyskinetic movement suggest that an up-regulation of DA receptors in the striatum corresponds with an improvement of dyskinesia in the IDPN-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Ischemia-induced changes in alpha-tubulin and beta-actin mRNA in the gerbil brain and effects of bifemelane hydrochloride.

Using in situ hybridization histochemistry, we examined changes in the cytoskeletal protein alpha-tubulin and beta-actin mRNAs in the gerbil brain 14 days after transient ischemia. In an attempt to identify the changes induced in the synthesis of cytoskeletal protein by ischemia, we also evaluated the effects of post-ischemia administration of bifemelane on these cytoskeletal proteins. alpha-Tubulin and beta-actin mRNAs were decreased in the CA1 region 14 days after transient ischemia. These decreases coincided with the loss of CA1 pyramidal cells, suggesting that they may have been related to delayed neuronal death. The beta-actin mRNA level in ischemic controls was significantly increased in the dentate gyrus, habenular nucleus, and medial and lateral thalamic nuclei, where some afferent nerves project into the hippocampal pyramidal cells. The increased beta-actin mRNA suggests that there may be a compensatory enhancement of actin synthesis in the afferent neurons that restores loosened synaptic connections with the ischemic cells in the CA1-4 fields. Administration of bifemelane just after recirculation prevented most of the ischemia-induced mRNA reductions in the CA1 field. Bifemelane's effect may be related to inhibition of Ca2+ influx and its radical scavenging activity. When bifemelane was administered to the ischemic group, alpha-tubulin mRNA levels significantly increased in the dentate gyrus and amygdaloid nucleus, and beta-actin mRNAs showed a tendency to increase in the CA3 and CA4 fields, dentate gyrus, and medial and lateral thalamic nuclei. These findings suggest that bifemelane may enhance synthesis of cytoskeletal protein, especially in the ischemic brain, inducing axon outgrowth or synapse formation.

Actins↗
PubMed1993

Regional changes in neuropeptide levels after 5,7-dihydroxytryptamine-induced serotonin depletion in the rat brain.

The levels of five neuropeptides (substance-P, somatostatin, cholecystokinin octapeptide, methionine-enkephalin and dynorphin) were examined in the brain and the spinal cord of rats 2 weeks after intracerebroventricular injection of 5,7-dihydroxytryptamine (5,7-DHT). 5,7-DHT injection caused a significant reduction of the serotonin level in all regions of the brain. The level of each neuropeptide except dynorphin significantly increased in specific regions of the brain after 5,7-DHT treatment without any decrease in their levels in any region. Since, coexistence and interaction between classical neurotransmitters and neuropeptides in the same neurons have been reported, both are indispensable for evaluating pathophysiological state of the brain function associated with abnormal neural transmission. The present findings together with previous reports suggest that neuropeptides act as neurotransmitters and compensate for the impaired function of the serotonergic systems.

5,7-Dihydroxytryptamine↗
PubMed1993

Rapid response of striatal muscarinic M1-receptor mRNA to muscarinic cholinergic agents in rat brain.

The effects of a single administration of muscarinic cholinergic agents on the level of muscarinic M1-receptor messenger RNA (M1-R mRNA) in the rat striatum were studied. Carbachol increased the M1-R mRNA expression rapidly and transiently, while trihexyphenidyl decreased it. These results suggest that muscarinic cholinergic agents participate in the positive regulation of muscarinic receptor mRNA in the early stage after treatment, contrary to the negative regulation in the chronic stage.

Animals↗
PubMed1993

[Effective treatment by bifemelane hydrochloride for emotional incontinence and regional blood flow in patient with cerebral infarction].

The authors report that bifermerane hydrochloride treatment improved emotional incontinence in patient with cerebral infarction. Before and after bifermerane hydrochloride treatment, 99mTc-HM PAO single photon emission CT (SPECT) was performed. After treatment, regional cerebral blood flows (CBF) in frontal lobe area increased selectively. These findings suggest that emotional incontinence and decreased CBF of the frontal lobe area were closely associated in this case.

Affective Symptoms↗
PubMed1993

Alterations in the binding of the phosphodiesterase inhibitor, rolipram, after transient ischemia in the gerbil brain.

To determine ischemia-induced changes in phosphodiesterase (PDE), changes in the membranous binding sites of rolipram, a cAMP-selective PDE inhibitor, were examined in the gerbil brain following transient 5 min forebrain ischemia. Coinciding with the delayed neuronal death (DND) in the hippocampal CA1 region, affinities for cerebral rolipram bindings decreased on Day 4, when intrinsic cAMP, substrate for PDE, might increase. The number of rolipram binding sites was significantly reduced in the hippocampus Day 14, despite the lack of change on Day 4. This reduction in rolipram binding was in agreement with the previously reported late onset reduction of muscarinic receptors, progressing more slowly than DND. Slowly progressive mechanisms may be involved in the ischemia-induced reduction of the hippocampal rolipram binding sites which may be PDEs.

Analysis of Variance↗