Biomedical subjects

M Asanuma

Publications and source records attributed to M Asanuma.

119 records · Page 7Linked to original sources

PubMedDate not supplied

Tubulin and actin mRNAs in the young-adult and the aged rat brain: effects of repeated administration with bifemelane hydrochloride.

In an attempt to identify the age-dependent changes in the potential synthesis of cytoskeletal proteins, we investigated changes in messenger RNA (mRNA) of alpha-tubulin and beta-actin in the young-adult and the aged rat brain using Northern blot analysis. alpha-Tubulin mRNA levels in the frontal cortex and hippocampus, and beta-actin mRNA levels in the hippocampus were significantly decreased in the aged rat brain. Age-dependent decreases in these mRNAs may be related to the neuronal dysfunction associated with aging, in addition to the reduction of several kinds of receptors previously reported. Repeated administration of bifemelane hydrochloride (4-(2-benzylphenoxy)-N-methylbutylamine hydrochloride) for 14 days increased the levels of beta-actin mRNA in the frontal cortex and the striatum of both young-adult and aged rats, although the effect of bifemelane treatment was smaller and not significant in the aged group. These results suggest that bifemelane treatment may enhance the synthesis of cytoskeletal protein and promote neural plasticity by inducing neurite growth or synapse formation.

Journal Article↗

PubMedDate not supplied

Chronic administration of acetylcholinesterase inhibitor in the senescent rat brain.

The effects of chronic administration of ENA-713, an acetylcholinesterase (AChE) inhibitor, on pre- and postsynaptic cholinergic indices were examined in the senescent rat brain. In the senescent group, the acetylcholine (ACh) level was markedly reduced in the frontal cortex, hippocampus, striatum and thalamus+midbrain, but these reductions were completely prevented by ENA-713. Moreover, although choline acetyltransferase (ChAT) activity was also significantly decreased in these four regions, it recovered in the frontal cortex, hippocampus and thalamus+midbrain after ENA-713 treatment. In contrast, cholinesterase (ChE) activity was not changed in any experimental groups. The maximum number (Bmax) of muscarinic M1 receptor (M1-R) binding site in the frontal cortex in the senescent group was decreased without any change in affinity, but this decrease was also inhibited by ENA-713. Thus, these findings suggest that ENA-713 may have protective, neurotrophic and therapeutic effects on aging-induced cholinergic dysfunction and be useful for the treatment of aging-related dementia, such as the Alzheimer-type dementia.

Acetylcholine↗

PubMedDate not supplied

Angiotensin II induces in vivo c-fos expression from rat renal cortex and medulla.

In order to verify whether angiotensin II (Ang II) induced in vivo protooncogene, c-fos, expression in the rat renal cortex and medulla, we administered various concentrations of Ang II to Wistar rats and measured the c-fos expression from the renal cortex and medulla using the method of Northern hybridization. c-fos expression induced by 1 microgram (1.6 x 10(-6) M) of atrial natriuretic peptide (ANP) was also examined. The result was that the peak expression of c-fos mRNA was observed at approximately 10 min after Ang II administration in both rat renal cortex and medulla. This expression was reduced to the control level at 30 min. The measurement of the concentration of injected-Ang II and c-fos mRNA expression revealed that the peak expression of c-fos mRNA in the renal cortex and medulla was detected at the concentration of 1.0 x 10(-8) M and 1.0 x 10(-9) M Ang II, respectively. Nevertheless, ANP had no significant effect on the increase in c-fos mRNA expression. These data revealed that Ang II transiently increases the in vivo c-fos expression in both rat renal cortex and medulla but ANP does not. This protooncogene expression may induce vascular and mesangial proliferation in the kidney.

Angiotensin II↗

PubMedDate not supplied

Chronic lisuride hydrogen maleate administration enhances muscarinic receptor binding in senescent rat brain.

Changes in the regional density of muscarinic-1 (M1) receptors and the effect of lisuride hydrogen maleate on these changes were studied in senescent rat brain by in vitro autoradiography. In young adult controls, M1 receptor binding was most dense in the striatum and hippocampus, followed by the cerebral cortex and amygdala. Binding to M1 receptors was markedly lower in these areas of the senescent brain compared with the young adult brain. These decreases were reversed by intraperitoneal administration of 50 micrograms/kg.day lisuride for 14 days. The present results indicate that the therapeutic efficacy of lisuride depends on normalization of not only monoamine systems but also acetylcholine systems.

Age Factors↗

PubMedDate not supplied

Effects of bromocriptine on dopamine turnover with or without levodopa.

Bromocriptine, a dopamine agonist, alleviates symptoms of Parkinson's disease, even when administered alone, and is used for its treatment. Better therapeutic effects are, however, achieved when bromocriptine is used in combination with levodopa. In this study, we examined the biochemical changes caused by bromocriptine administration with and without levodopa, and evaluated the effects of the treatments on dopamine turnover in the mouse striatum. Results show that dopamine turnover is suppressed by the administration of bromocriptine alone with a slight decrease in the amount of dopamine, and dopamine turnover is very strongly promoted by the administration of levodopa. When the two drugs are administered together, bromocriptine enhances the levodopa-induced increase in dopamine turnover in the striatum. These findings indicate that bromocriptine therapy in combination with levodopa enhances the dopaminergic function and suggest that the combination therapy of bromocriptine and levodopa shows good efficacy. The results of this study may, thus, provide a theoretical basis for the combination therapy of bromocriptine and levodopa.

Analysis of Variance↗

PubMedDate not supplied

Pitfalls in assessment of c-fos mRNA expression in the brain: effects of animal handling.

Immediate early genes are rapidly and transiently induced by many stimuli and produce their transcription factors. Of the immediate early genes, the proto-oncogene c-fos and its product Fos play a role in cell proliferation, differentiation and general signal transmission as the 'third messenger' regulating the transcription of other genes. Even minute stimuli such as the attachment of electrodes, needle injection and saline administration increase the level of c-fos mRNA expression in animal brains. It is, therefore, necessary to investigate the effects of using anesthetics and solvents for drug administration on c-fos expression in order to accurately assess net c-fos induction after stimulation. Furthermore, experimental procedures might themselves affect c-fos mRNA expression in the brain after in vivo stimulation. In this review, we discuss technical pitfalls in assessing in vivo c-fos expression. Rough handling with repeated saline administration enhanced cortical c-fos mRNA expression in the rat brain after a single saline injection by increasing baseline c-fos mRNA levels. In contrast, gentle handling with repeated saline administration diminished c-fos mRNA expression after a single injection by decreasing baseline c-fos mRNA levels. These two types of handling with the repeated injection led to diametrically opposite results on c-fos mRNA expression after a single stimulation. Our results suggest that c-fos mRNA induction after a single stimulation might be affected by the types or intensities of animal handling and that effects of animal handling must be considered when estimating c-fos mRNA induction.

Animals↗

PubMedDate not supplied

Effects of bifemelane hydrochloride on loss of N-methyl-D-aspartate receptor and muscarinic cholinergic receptor binding in the gerbil hippocampus after transient ischemia.

The effects of bifemelane hydrochloride on changes of N-methyl-D-aspartate receptors and muscarinic cholinergic receptors were examined in the gerbil hippocampus after transient ischemia with radioactive-specific ligands. There were marked reductions in both these receptors in the gerbil hippocampus 14 days after transient ischemia, without changes in the respective affinities. Post-ischemia bifemelane treatment almost completely prevented the ischemia-induced decreases in the numbers of these receptors, and had no effect in sham-operated controls. The results of the present study suggest that this drug prevents postsynaptic dysfunction induced by transient ischemia, and may be useful in the therapy of both the chronic and the acute stage of cerebrovascular disease.

Animals↗

PubMedDate not supplied

Effects of chronic administration of lisuride hydrogen maleate on aromatic amine and metabolite levels in the gerbil brain following bilateral common carotid ligation.

Cerebral monoaminergic neurotransmitters and their metabolites show various concentration changes in gerbils following bilateral carotid ligation. The present study evaluated the effect of chronic administrations of lisuride hydrogen maleate (lisuride) on these changes. Lisuride (0.01 mg/kg or 0.05 mg/kg) or vehicle was intraperitoneally administered to gerbils for 14 consecutive days before the induction of a 30 min ischemia by bilateral carotid ligation. Animals were sacrified immediately and the levels of dopamine, DOPAC, homovanillic acid, noradrenaline, serotonin and 5-hydroxyindoleacetic acid determined by HPLC in the striatum, cortex, hippocampus and diencephalon/midbrain. Lisuride itself had no effect on any compound determined in any region. In the carotid-ligated gerbil brain, however, lisuride corrected the reduction of dopamine in the striatum, normalized or reduced increases in the (DOPAC+homovanillic acid)/dopamine ratio in the striatum, hippocampus and diencephalon/midbrain, and increased the levels of serotonin in all four regions. The present study, together with previous reports, indicate that lisuride may interfere with ischemia-induced cerebrovascular disturbances and, in such a way, improve some pathological sequelae of cerebrovascular disease.

Animals↗

PubMedDate not supplied

Effects of chronic administration of mergocryptine on changes in neurotransmitter levels in the ischemic gerbil brain.

Changes in various neurotransmitter systems of the gerbil brain during ischemia and the effects of administration of mergocryptine, a new ergot derivative, were studied. Gerbils intraperitoneally administered 0.5 mg/kg of mergocryptine or the vehicle once a day for 14 days were used. The administration of mergocryptine to control animals had no effect on the contents of neurotransmitters or their metabolites in various regions of the brain, but it corrected abnormalities in the neurotransmitter systems caused by ischemia. These results suggest the usefulness of mergocryptine against the deleterious effects of brain ischemia.

3,4-Dihydroxyphenylacetic Acid↗

PubMedDate not supplied

Effects of the acetylcholinesterase inhibitor ENA-713 on ischemia-induced changes in acetylcholine and aromatic amine levels in the gerbil brain.

The effects of a new acetylcholinesterase inhibitor, ENA-713, on ischemia-induced changes in acetylcholine, monoamines, and their metabolites, were studied in the gerbil. ENA-713 (0.2 mg/kg) or saline was administered intraperitoneally to gerbils 30 min before induction of cerebral ischemia by bilateral carotid occlusion. Pretreatment with ENA-713 mitigated the ischemia-induced abnormalities of the cholinergic, dopaminergic and serotoninergic systems in the gerbil brain, although it had virtually no effect on acetylcholine, monoamines, or their metabolites in any region of the normal gerbil brain. These findings suggest that ENA-713 has beneficial effects against ischemia-induced cerebral disorders. Thus, ENA-713 seems to be promising as a preventive or therapeutic agent for cerebrovascular dementia due to cerebral ischemia and might be useful for the treatment of Alzheimer-type dementia which is associated with multiple neurotransmitter abnormalities in the brain.

Acetylcholine↗

PubMedDate not supplied

Protective effects of pergolide on dopamine levels in the 6-hydroxydopamine-lesioned mouse brain.

Pergolide, along with bromocriptine and lisuride, is one of the most active dopamine receptor agonists. To determine whether or not pergolide protects against dopaminergic neuronal damage, via its activity on monoamine metabolism, we studied the effects of pergolide pretreatment on changes in monomaines and their metabolites in the mouse striatum after intracerebroventricular injection of 6-hydroxydopamine with pretreatment of desipramine. After intracerebroventricular administration of 6-hydroxydopamine (40 micrograms) in mice, the levels of dopamine and its metabolites (DOPAC, HVA) in the striatum rapidly decreased to 49%, 29% and 68%, respectively, of the naive controls at week 1 but then gradually recovered to control levels at weeks 2 and 4. Repeated pretreatment with pergolide (0.5 mg/kg, i.p.) for 7 days before administration of 6-hydroxydopamine, almost completely protected against reduction in striatal dopamine and its metabolites 1 week after injection of 6-hydroxydopamine. Therefore, pergolide could normalize the decreased dopamine synthesis or storage, and has a neuroprotective effect against dopaminergic dysfunction induced by the neurotoxin, 6-hydroxydopamine. Although we found that pergolide did not show radical scavenging activity in an in vitro system that generated hydroxyl radicals, it has been reported in vivo that pergolide treatment may induce Cu/Zn superoxide dismutase in the rat striatum. Considering these findings, pergolide may well be protective to dopaminergic neurons, largely because of its effects on presynaptic autoreceptors and on its induction of Cu/Zn superoxide dismutase. Further research on the neuroprotective effects of pergolide in Parkinson disease models, by injection of 6-hydroxydopamine, is needed to clarify its mechanism of action on dopaminergic indices.

3,4-Dihydroxyphenylacetic Acid↗